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TW200836743A - Quinazolinone and fused pyrimidinone compounds and their use in treating sodium channel-mediated diseases or conditions - Google Patents

Quinazolinone and fused pyrimidinone compounds and their use in treating sodium channel-mediated diseases or conditions Download PDF

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TW200836743A
TW200836743A TW097103383A TW97103383A TW200836743A TW 200836743 A TW200836743 A TW 200836743A TW 097103383 A TW097103383 A TW 097103383A TW 97103383 A TW97103383 A TW 97103383A TW 200836743 A TW200836743 A TW 200836743A
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Shifeng Liu
Jian-Yu Sun
Robert Fraser
Jianmin Fu
Rajender Kamboj
Duanjie Hou
Serguei Svirdov
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Xenon Pharmaceuticals Inc
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Abstract

This invention is directed to compounds of formula (I): wherein , n, R1, R2 and R3 are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Description

200836743 九、發明說明： 【發明所屬之技術領域】 本發明係針對喹唑啉酮與稠合嘧啶酮化合物，包含該化 合物之醫藥組合物，及使用該化合物與醫藥組合物以治療 納通道所媒介之疾病或症狀，譬如疼痛，以及其他與鈉通 道之媒介有關聯疾病與症狀之方法。 【先前技術】 會在神經、肌肉及其他電易激細胞中引發作用電位之電 壓選通鈉通道跨膜蛋白質，係為正常知覺、情感、思考及 動作之必要成份（Catterall, W.A·，Atowre (2001)，第 409 卷，第 988-990頁）。此等通道包含高度經處理之α亞單位，其係與輔 助/3亞單位有關聯。會形成孔隙之α亞單位係足供通道功 能用，但通道選通之動力學與電壓依存性，係一部份被/3 亞單位修改（Goldin等人，(2000)，第28卷，第365-368頁） 。各α_亞單位含有四個同系功能部位I至IV，各具有六個預 測之跨膜鏈段。會形成離子傳導孔隙且含有會調節鈉離子 傳導之電壓感測器之鈉通道α-亞單位，具有相對分子質量 為260,000。電生理學記錄、生物化學純化及分子無性繁殖， 已確認十種不同鈉通道α亞單位與四種卢亞單位（Yu，F.H. 等人，5W. S7KE (2004)，253 ;與 Yu，F.H·等人，A^mscz·. (2003)，20 ·· 7577-85)。 鈉通道之正字標記包括當越過易激細胞漿膜之電壓被去 極化（電壓依賴性選通），且鈉離子有效與選擇性傳導經過 對蛋白質結構固有之傳導孔隙時之快速活化與失活（SatO, Ο- ΐ 28409 200836743 等人，(2001)，409，1047-1051)。在負或過度極化膜電位 下，納通道係被關閉。在細胞膜去極化作用後，納通道會 迅速地開啟，然後失活。通道僅在開啟狀態中傳導電流， 而一旦失活，在其可重開之前，即必須返回靜止狀態，藉 由細胞膜過度極化作用促成。不同鈉通道亞型係在其活化 與失活下之電壓範圍以及其活化與失活動力學中改變。 蛋白質之鈉通道族群已被廣泛地研究，且証實係涉及多 種生命體功能。在此領域上之研究已確認《亞單位之變型， 其會造成通道功能與活性上之主要改變，其最終可導致主 要病理生理學症狀。隨著功能所隱含，此蛋白質族群係被 視為治療介入之引動點。Nav U與Nav 1.2係高度地表現於腦 部中（Raymond，C.K·等人，J·所〇/· Cfem· (2004)，279(44): 46234-41)， 且對正常腦部功能為重要的。在人類中，於Nav 1.1與Nav 1.2 中之突變，會造成嚴重癲癇狀態，而在一些情況中，為精 神衰退（Rhodes，T.H.等人，ZVoc. TVai/· 6W· (2004)，101 (30): 11147-52; Kamiya，Κ·等人，《/· C/zem. (2004)，24(11): 2690·8 ; Pereira，S·等人，Λ^/w/ogy (2004)，63(1) : 191-2)。因此， 兩種通道已被認為是用於治療癲癇之經確認有效標的（參 閱PCT公告之專利公報案號WO 01/38564)。200836743 IX. Description of the Invention: [Technical Field] The present invention relates to a quinazolinone and a fused pyrimidinone compound, a pharmaceutical composition comprising the same, and a pharmaceutical composition for treating a nanochannel medium Diseases or symptoms, such as pain, and other methods associated with the media and channels of sodium channels. [Prior Art] Voltage-gated sodium channel transmembrane proteins that trigger action potentials in nerves, muscles, and other electro-active cells, essential for normal perception, emotion, thinking, and action (Catterall, WA·, Atowre ( 2001), Vol. 409, pp. 988-990). These channels contain highly processed alpha subunits that are associated with the auxiliary/3 subunit. The alpha subunit system that forms the pores is sufficient for channel function, but the dynamics and voltage dependence of the channel gating are partially modified by the /3 subunit (Goldin et al., (2000), Vol. 28, p. 365-368 pages). Each α_ subunit contains four homologous functional sites I to IV, each having six predicted transmembrane segments. The sodium channel alpha-subunit, which forms ion-conducting pores and contains a voltage sensor that regulates sodium ion conduction, has a relative molecular mass of 260,000. Electrophysiological recording, biochemical purification and molecular vegetative propagation, ten different sodium channel alpha subunits and four luya units have been identified (Yu, FH et al, 5W. S7KE (2004), 253; and Yu, FH · et al., A^mscz·. (2003), 20 · 7577-85). The positive label of the sodium channel includes rapid deactivation (voltage-dependent gating) when the voltage across the stimuli of the stimulatory cell membrane is passed, and rapid activation and deactivation of the sodium ion efficiently and selectively through the conductive pores inherent to the protein structure ( SatO, Ο-ΐ 28409 200836743 et al. (2001), 409, 1047-1051). At negative or excessively polarized membrane potentials, the nanochannel system is turned off. After depolarization of the cell membrane, the nanochannel will open rapidly and then inactivate. The channel conducts current only in the on state, and once deactivated, it must return to a quiescent state before it can be reopened, which is facilitated by excessive membrane polarization. Different sodium channel subtypes vary in their voltage range under activation and deactivation as well as in their activation and inactivation mechanics. The sodium channel population of proteins has been extensively studied and has been shown to be involved in a variety of life functions. Studies in this area have identified variants of subunits that cause major changes in the function and activity of the channel, which can ultimately lead to major pathophysiological symptoms. As the function implies, this protein family is considered to be the trigger point for therapeutic intervention. The Nav U and Nav 1.2 lines are highly expressed in the brain (Raymond, CK et al., J. S./Cfem. (2004), 279(44): 46234-41), and for normal brain function. important. In humans, mutations in Nav 1.1 and Nav 1.2 cause severe epileptic states, and in some cases, mental decline (Rhodes, TH et al., ZVoc. TVai/· 6W· (2004), 101 (30 ): 11147-52; Kamiya, Κ· et al., // C/zem. (2004), 24(11): 2690·8; Pereira, S. et al., Λ^/w/ogy (2004), 63(1) : 191-2). Therefore, both channels have been considered to be validated targets for the treatment of epilepsy (see PCT Publication No. WO 01/38564).

Nav 1.3係廣泛地表現於全身中（Raymond，C.K.等人，在J：文 分遂之著作尹）。已証實在神經系統損傷後，於大白鼠之背 側角感覺神經元中，具有其向上調節之表現（Hains，B.D.等人, J· (2003)，23(26) : 8881-92)。在此領域中之許多專家已 將Nav 1.3視為疼痛治療劑之適當標的（Lai，J.等人，CWr.办如. 128409 200836743 (2003)，（3): 291-72003; Wood，J.N·等人，J· A^/rMzb/· (2004)， 61(1) : 55-71 ; Chung，J.M.等人，iSymp. (2004)，261 : 19-27 ;討論 27-31，47-54)。The Nav 1.3 system is widely expressed throughout the body (Raymond, C.K. et al., J: Text, 遂 遂 尹). It has been demonstrated that after neurological injury, the sensory neurons in the dorsal horn of the rat have an upward regulation (Hains, B. D. et al., J. (2003), 23(26): 8881-92). Many experts in this field have identified Nav 1.3 as an appropriate target for pain therapeutics (Lai, J. et al., CWr., et al. 128409 200836743 (2003), (3): 291-72003; Wood, JN· Et al., J. A^/rMzb/· (2004), 61(1): 55-71; Chung, JM et al., iSymp. (2004), 261: 19-27; Discussion 27-31, 47-54 ).

Nav 1.4表現基本上係受限於肌肉（Raymond，C.K.等人，名2 文歹/遽之著#户）。在此基因中之突變已被証實對於肌肉功 能具有深遠作用’包括麻痒（Tamaoka，A.，Afei. (2003)，（9): 769-70)。因此，此通道可被視為用於治療異常肌肉收縮性、 痙攣或麻痒之標的。 心臟鈉通道Nav 1.5係主要被表現於心室與心房中 (Raymond，C.K·等人，在上文歹/遂之著作尹），且可被發現於 竇房節、室節及可能之浦金埃氏細胞中。心臟作用電位之 快速上衝與快速脈衝傳導經過心臟組織，係由於Nav 1.5之 打開所致。因此，Nav 1.5係為心節律不齊起源之中樞。於 人類Nav 1.5中之突變會造成多發性節律不齊徵候簇，包括 例如長QT3 (LQT3)、Brugada徵候簇（BS)、遺傳心臟傳導缺陷、 突然意外夜間死亡徵候簇（SUNDS)及突然嬰兒死亡徵候簇 (SIDS) (Liu，H·專人，乂所.J· (2003)，3(3) : 173-9) 〇 鈉通道阻斷劑療法已被廣泛地使用於治療心節律不齊。於 1914年發現之第一種抗節律不齊藥物奎尼定，係被分類為 鈉通道阻斷劑。The performance of Nav 1.4 is basically limited by muscle (Raymond, C.K. et al., name 2 歹文/遽之之##). Mutations in this gene have been shown to have profound effects on muscle function' including itching (Tamaoka, A., Afei. (2003), (9): 769-70). Therefore, this channel can be considered as a marker for the treatment of abnormal muscle contraction, spasms or itching. The cardiac sodium channel Nav 1.5 is mainly expressed in the ventricles and atrium (Raymond, CK et al., in the above 歹/遂, Yin), and can be found in the sinus node, ventricular ganglia and possibly Pujin In the cell. The rapid overshoot and rapid pulse conduction of cardiac action potentials through the heart tissue are due to the opening of Nav 1.5. Therefore, the Nav 1.5 system is the origin of the heart rhythm. Mutations in human Nav 1.5 cause multiple rhythm syndrome clusters including, for example, long QT3 (LQT3), Brugada syndrome (BS), genetic heart conduction defects, sudden accidental nighttime death syndrome (SUNDS), and sudden infant death Syndrome (SIDS) (Liu, H. Specialist, 乂所. J. (2003), 3(3): 173-9) Sodium channel blocker therapy has been widely used to treat cardiac arrhythmias. The first anti-arrhythmic drug, quinidine, discovered in 1914, was classified as a sodium channel blocker.

Nav 1.6係使在整個中樞與末梢神經系統中發現，群集於 神經軸索之Ranvier節中之大量廣泛地分佈之電壓選通鈉通 道編碼（Caldwell，J.H·等人，pwc·池从也沉/·制· USA (2000)， 97(10) : 5616-20)。雖然在人類中未曾檢出突變型，但Nay 16 128409 200836743 係被認為在與多發性碩介古, 、 Γ生更化有關聯病徵之表象中扮演一項角 色，且已被認為是治療此 夭7丙《知的（Craner，等人，proc. 層」⑽/·&/· USA (2004)，101(21) ·· 8168·73)。 v係首先無性繁殖自親鉻細胞瘤⑽2細胞系 (Toledo-Aral, JJ. # Λ? ^ ^ ^ f 1532)。其在高含量下存在於小直徑神經元之生長錐細胞 :’指出其可在感受傷害訊息之傳遞中扮演一項角色。惟 沒已被此領域之專家挑戰，因Ν〜17亦被表現於與自主系 ^ # II I# ^ # Μ ^ ^ ^ ^ „ t (Klugbauer5 λ ^ \m〇 ^ (1995)，14⑹··隱90)，且其本身已牵連自主過程。於自主功 能中之隱含角色係以無~.7突變種之產生而証實；刪除 所有感官與交感神經元中之NavlJ會造成致死出生前後表 現型（Nassar等人，户⑽施?/」撕/·制USA (2〇〇4)，1〇1(34): 12706-11)。對照上而言，在主要為感受傷害之感覺神經元之 個子集中，藉由刪除Nav 17表現，在疼痛機制中之一種 角色，係經証實（Nassar等人，在上文歹/逑之著作户）。進一 步支持Navl.7阻斷劑在神經元之一個子集中為活性，係被 乂下fx現所支持，兩種人類可遺傳之疼痛症狀，原發性肢 端紅痛病與豕族性直腸疼痛，已被証實係形成圖譜至Nav 1.7 (Yang，Y.等人，施/· Ge贼（2004)，41(3) : 171-4)。The Nav 1.6 system is found throughout the central and peripheral nervous systems, and a large number of widely distributed voltage-gated sodium channel codes clustered in the Ranvier section of the axons (Caldwell, JH et al., pwc. USA · (2000), 97 (10) : 5616-20). Although no mutants have been detected in humans, Nay 16 128409 200836743 is thought to play a role in the appearance of multiple associated diseases, and has been considered to treat this disease. 7 C. "Craner, et al., proc. layer (10) / · & / · USA (2004), 101 (21) · · 8168 · 73). v is the first asexual reproduction of the auto-chromoblastoma (10) 2 cell line (Toledo-Aral, JJ. # Λ? ^ ^ ^ f 1532). It is present in high-content growth cones of small-diameter neurons: ' indicates that it can play a role in the transmission of nociceptive messages. However, it has not been challenged by experts in this field, because Ν~17 is also expressed in the autonomous system ^ II I# ^ # Μ ^ ^ ^ ^ „ t (Klugbauer5 λ ^ \m〇^ (1995), 14(6)·· Hidden 90), and itself has been implicated in the autonomous process. The hidden role in autonomic function is confirmed by the generation of no ~.7 mutant species; deleting all NavlJ in sensory and sympathetic neurons will result in lethal phenotype before and after birth. (Nassar et al., household (10) Shi?/" tearing / system USA (2〇〇4), 1〇1 (34): 12706-11). In contrast, in a subset of sensory neurons that are primarily nociceptive, a role in the pain mechanism is confirmed by the deletion of Nav 17 (Nassar et al., 歹/逑). Further support for Navl.7 blockers in a subset of neurons is active, supported by underarm fx, two human hereditary pain symptoms, primary acral red pain and steroidal rectal pain It has been confirmed that the map was formed to Nav 1.7 (Yang, Y. et al., Shi Ge Ge (2004), 41 (3): 171-4).

Nav 1.8之表現基本上係被限制於〇11(}(1^卿〇地^1等人 文々遂之著作户）。關於Nav 1.8沒有經確認之人類突變 型。但是’無Nav 1.8之突變老鼠係存活、能生育及正常外 觀。對有害機械刺激之顯著止痛，在有害熱感受上之小缺 128409 200836743 失，及炎性痛覺過敏之延遲發展，係對研究人員指出Nav 1.8 在疼痛發出訊息上係扮演一項主要角色（Akopian，A.N.等人， 論(1999)，2(6) ·· 541-8)。此通道之阻斷係廣泛地被接 受為對疼痛之潛在治療（Lai，J等人，在上文遂之著作户； Wood，J.N·等人，在J:文歹/遂之著作户；Chung，J.M.等人，在 上文Θ述之著#尹）。PCT公告之專利申請案WO 03/037274A2 係描述吡唑-醯胺類與磺醯胺類，用於治療中樞或末梢神經 系統症狀，特別是疼痛與慢性疼痛，其方式是阻斷與所顯 示症狀之展開或復發有關聯之鈉通道。PCT公告之專利申 請案WO 03/037890A2係描述六氫吡啶類，以治療中樞或末梢 神經系統症狀，特別是疼痛與慢性疼痛，其方式是阻斷與 所顯示症狀之展開或復發有關聯之鈉通道。此等發明之化 合物、組合物及方法係特別可用於治療神經病原性或炎性 疼痛，其方式是抑制離子通量經過包含PN3 (Nav 1.8)亞單位 之通道。 由Dib-Hajj，S.D.等人所揭示之河豚毒素不敏感之末梢鈉通 道 Nav 1.9 (參閱 Dib-Hajj，S.D·等人，乃w·術汶 dcW· 5W· USA (1998)， 95(15) ·· 8963-8)係經証實僅留駐在背側根部神經節中。已証 實Nav 1.9係成為神經營養素（BDNF)所引起之去極化作用與 興奮之基礎，且為經証實被配位體所媒介電壓選通鈉通道 超族群之唯一成員（Blum，R·，Kafitz，K.W·，Konnerth，A·，Λ/αίζ/re (2002)，419(6908) : 687-93)。表現此通道之有限型式已使其成 為治療疼痛之候選標的（Lai，J等人，在2文分逑之著作户； Wood，J.N·等人，在上文办逑之著#尹；Chung，J.M.等人，在 128409 -10- 200836743 上文引述之著作中、。The performance of Nav 1.8 is basically limited to 〇11(}(1^卿〇地^1, etc.). There is no confirmed human mutant for Nav 1.8. But 'no Nav 1.8 mutant mouse Survival, fertility and normal appearance. Significant pain relief for noxious mechanical stimuli, loss of harmful thermal sensation 128409 200836743 Loss, and delayed development of inflammatory hyperalgesia, the researchers pointed out that Nav 1.8 in the pain message The Department plays a major role (Akopian, AN et al., (1999), 2(6) · 541-8). The blockade of this channel is widely accepted as a potential treatment for pain (Lai, J, etc.) Person, in the above-mentioned book; Wood, JN·, etc., in J: Wenyu/遂之书; Chung, JM, et al., narration of #尹). Patent application for PCT announcement WO 03/037274 A2 describes pyrazole-guanamines and sulfonamides for the treatment of central or peripheral nervous system symptoms, particularly pain and chronic pain, by blocking the association with the onset or recurrence of the indicated symptoms. Sodium channel. Patent Application No. WO 03/037890A2 to PCT Publication Depicting hexahydropyridines to treat central or peripheral nervous system symptoms, particularly pain and chronic pain, by blocking sodium channels associated with the onset or recurrence of the indicated symptoms. Compounds, compositions and methods of the invention It is particularly useful for the treatment of neuropathic or inflammatory pain by inhibiting ion flux through passages containing PN3 (Nav 1.8) subunits. Tetrodotoxin-insensitive terminal sodium as revealed by Dib-Hajj, SD et al. Channel Nav 1.9 (see Dib-Hajj, SD et al., v. shuwen dcW·5W· USA (1998), 95(15) · 8963-8) has been confirmed to reside only in the dorsal root ganglion The Nav 1.9 line has been shown to be the basis for depolarization and excitability caused by neurotrophins (BDNF) and is the only member of the sodium channel supergroup that has been shown to be mediated by the voltage of the ligand (Blum, R·, Kafitz, KW·, Konnerth, A·, Λ/αίζ/re (2002), 419(6908): 687-93). The limited pattern of this channel has made it a candidate for treatment of pain (Lai, J et al. , in the writing of 2 articles; Wood, JN, etc. Man, in the book above, #尹; Chung, J.M. et al., in the works cited above, 128409 -10- 200836743.

NaX為推斷之鈉通道，其尚未經註實為電壓選通。除了 表現於肺臟、心、臟、背側根部神經節及末梢神經系統之 Schwann細胞中以外，NaX已被發現於神經元與室管膜細胞 中，在CNS之限制區域中，特別是在室周圍器官中，其係 涉及體液等穩性(Watanabe，E.等人，j —圖' (2〇〇〇)，2卿 7743-51)。無NaX之老鼠在水_與鹽_耗乏之條件下，顯示異 f ㈣取高滲性鹽水。此等發現指出贿在體液鈉含量之中 '柩感覺與鹽攝取行為之調節上，扮演-項重要角色。其表 現里式14功月b建議其作為治療膽囊纖維變性及其他相關鹽 調節病恙之標的。 以用來降低腦部某些區域中神經元活性之鈉通道阻斷劑 ’可豚毋素(TTX)之研究’顯示其在上瘾治療上之潛在用途。 樂物配對之刺激會在大白鼠中誘出藥物癖好與上癌之復發 及藥物尋找行為。底與外側扁桃體（BLA)之功能完整性，係 ( 為藉由古柯鹼所調節刺激所誘出之古柯鹼尋找行為之恢復 所必肩，但並非藉由古柯鹼本身。BLA在海洛因尋找行為 之恢復上，係扮演類似角色。BLA對於在大白鼠模式中已 肖失海/〇因哥找行為之經調節與海洛因引動恢復之ττχ_所 I 致失活（Fuchs，R.A.與 See，R.E·，吻以咖㈣2㈣/卿（2002) 160(4): 425-33) 〇 _此⑴切相關蛋白質族群長久以來已被認定為治療介入之 標的。鈉通道係被各種不同陣列之藥理劑作為標的。其包 括神、、工毋素、I几節律不齊藥、抗搐搦藥及局部麻醉劑（C1批e， 128409 200836743 J.J.等人，趨/七藥勿發麂（2000) 5 : 506-520)。作用於鈉通道之 所有現行藥理劑，具有受體位置在α亞單位上。至少六個 不同受體位置供神經毒素用，與一個受體位置供局部麻醉 劑及相關藥物用，已被確認（Cestele，s·等人，所〇c/zz>m.e (2〇〇〇)， 第 82 卷：883-892)。 小分子鈉通道阻斷劑或局部麻醉劑及相關抗癲癎藥與抗 節律不齊藥物，會與位於鈉通道孔隙内腔中之重疊受體位 置交互作用（Catterall，W.A·，#,經元（2〇〇〇), 26 : 13-25)。在得自 四個功能部位之至少三個之S6鏈段中之胺基酸殘基，係有 助於此複合藥物受體位置，其中IVS6鏈段係扮演優勢角色。 此等區域係高度地保守，且因此迄今已知之大部份鈉通道 阻斷劑，會以類似功效，與所有通道亞型交互作用。雖然 如此’已能夠產生具有治療選擇性與足夠治療窗口之納通 道阻斷劑，以治療癲癇（例如拉莫三寧（lam〇trignine)、苯妥英 及胺甲醯氮萆)與某些心節律不齊藥(例如利多卡因、托卡 因奈得（tocainide)及慢心利（mexiletine))。但是，此等阻斷劑之 功效與治療指數並非最適宜，且已限制此等化合物在盆中 納通道阻斷劑係為理想上適合之多種治療領域中之 性。 、 急性與慢性疼痛之處理 包括新生兒、嬰兒及兒童NaX is the inferred sodium channel, which has not yet been annotated as a voltage gate. In addition to Schwann cells found in the lungs, heart, viscera, dorsal root ganglia, and peripheral nervous system, NaX has been found in neurons and ependymal cells, in restricted areas of the CNS, particularly in the periventricular organs. Among them, it is related to the stability of body fluids (Watanabe, E. et al., j-Fig. (2〇〇〇), 2 Qing 7743-51). Rats without NaX showed hypertonic saline under conditions of water and salt _ consumption. These findings point out that bribe plays an important role in the regulation of sodium sulphate and salt uptake. Its expression 14 is recommended as a target for the treatment of gallbladder fibrosis and other related salt-regulating diseases. The use of a sodium channel blocker, the guanosin (TTX) study, which is used to reduce neuronal activity in certain areas of the brain, has shown its potential use in addictive treatment. The stimulating of the music pair will induce drug relapse and cancer recurrence and drug search behavior in the rats. The functional integrity of the base and lateral tonsil (BLA) is the recovery of cocaine-seeking behavior induced by cocaine-mediated stimulation, but not by cocaine itself. BLA in heroin In the search for behavioral recovery, the system plays a similar role. BLA is inactivated by the adjustment of the heroic behavior in the rat model and the recovery of heroin evokes (Fuchs, RA and See, RE·, kiss Essence (4) 2 (4)/Qing (2002) 160(4): 425-33) 〇_This (1) cut-related protein group has long been recognized as the target of therapeutic intervention. Sodium channel is a pharmacological agent of various arrays As a target, it includes God, work sputum, I arrhythmia, anticonvulsants and local anesthetics (C1 batch e, 128409 200836743 JJ, etc., trend / seven drugs do not worry (2000) 5 : 506- 520). All current pharmacological agents acting on the sodium channel have a receptor position in the alpha subunit. At least six different receptor sites are available for neurotoxins, and a receptor site for local anesthetics and related drugs has been used Confirmation (Cestele, s· et al. c/zz>me (2〇〇〇), Vol. 82: 883-892. Small molecule sodium channel blockers or local anesthetics and related anti-epileptic drugs and anti-arrhythmic drugs, which are located in the sodium channel pores Overlapping receptor position interactions in the lumen (Catterall, WA·, #, Jing Yuan (2〇〇〇), 26: 13-25). In the S6 segment obtained from at least three of the four functional parts The amino acid residues contribute to the location of this complex drug receptor, where the IVS6 segment plays a dominant role. These regions are highly conserved, and thus most of the sodium channel blockers known to date will Similar effects, interacting with all channel subtypes. However, it has been able to produce nanochannel blockers with therapeutic selectivity and adequate therapeutic window for the treatment of epilepsy (eg lam〇trignine, phenytoin and Amoxicillin) and certain cardiac rhythm disorders (such as lidocaine, tocainide, and mexiletine). However, the efficacy and therapeutic index of these blockers are not the most Suitable, and have restricted the use of these compounds in the basin of the nanochannel blocker Suitable for a variety of therapeutic areas in the nature of the ideal., Treatment of acute and chronic pain, including newborns, infants and children

藥物療法為在所有年齡群中，包 處理急性與慢性疼痛之唯一依靠。 學會分類成三個主要種類·· U非爸 128409 -12- 200836743 如阿斯匹靈），2)類阿片止痛劑，及3)共止痛劑。 ΓDrug therapy is the only reliance on acute and chronic pain in all age groups. Learn to classify into three main categories: U non-dad 128409 -12- 200836743 such as aspirin), 2) opioid analgesics, and 3) total analgesics. Γ

非類阿片止痛劑，譬如乙醯胺吩，與NSAID，可用在由 於多種原因所致之急性與慢性疼痛，包括手術、創傷、關 即炎及癌症。NSAID為涉及發炎之疼痛所需要，因為乙醯 胺吩缺乏消炎活性。類阿片亦缺乏消炎活性。所有nsaid 均會抑制環氧化酶（COX)，於是抑制前列腺素合成，且降低 火！生疼痛回應。有至少兩種C〇x異構重組物，cox·〗與c〇x_2 。常用非選擇性cox抑制劑包括異丁苯丙酸（ibupr〇fen)與那 丙新（napr〇xen)。COX-丨係被發現於血小板、⑶道、腎臟及大 部份其他人類組織中，其抑制係被認為是與不利作用譬如 胃腸出血有關聯。選擇性COX-2NSAH)之發展，譬如塞拉庫 西比（celecoxib)、維德庫西比（valdec〇xib)及羅費庫西比 (mfecoxib)，具有非選擇性Ν_之利益，伴隨著降低腸與腎 臟中之不利作用形態。但是’目前証據指出某些選擇性 COX-2抑制劑之慢性用途可能會造成增加中風發生之危險。 類阿片止錢之利關由美國㈣學會所建議，以疼痛 指向之病歷及包括重複疼痛評估之身體為基礎被引發。由 於伴隨著阿片製劑利用夕+ & 丁 U ^ 乃衣釗和用之見廣不利作用形態，故療法應包 括診斷、整合各學科間治療計劃及適當現行病患監測。進 一步建議類阿片應被添加至非類阿片，以處理急性疼痛及 對單獨非類阿片不會回摩产 W應之癌症相關疼痛。類阿片止痛劑 係在中樞與末梢神㈣統中，對M/c類型之專-受體充 作催動劑。依類阿片及其配方或投藥模式而定，其可具有 較短或較長延續時間。所有類卩m錢均具有會造成呼 128409 13 200836743 吸抑鬱、肝衰竭、上癩及依賴性之危險，且其本身對長期 或慢性疼痛處理並不理想。 ^ 許多其他藥物種類可加強類阿片或NSA][d之作用，在某 些=中具有獨立止痛活性，或會中和止痛劑之副作用了 不管藥物具有其中何種作用，其係被總稱為”共止痛劑"。 三環狀抗抑鬱劑、抗癲癇藥藥物、局部麻醉劑、類皮質糖、 骨骼肌鬆弛劑、抗痙攣劑、抗組織胺類、苯并二氮七圜類、 咖啡驗、局部藥劑(例如辣椒素)、右旋安非他命及紛::井 類，全被使用於臨床上，作為輔助療法或個別用於治療疼 痛。特別是抗癲癇藥物在治療疼痛症狀上已享有若干程度 Μ # °❹’加巴潘亭（Gabapentin) ’其具有未經確認之治 f標的’其係為神經病原性疼痛所需要。其他臨床試驗正 鲁試確立中樞神經病原性疼痛可回應離子通道阻斷劑，譬 士 2納及/或NMDA(N-甲基_D-天冬胺酸鹽）通道之阻斷劑。 目别在發展中者係為低親和力NMDA通道阻斷劑，用於治 療神經病原性疼痛。文獻係提供實質臨站前電生理學註據^ 支持利用NMDA拮抗劑以治療神經病原性疼痛。此種藥劑 亦發現可在對類阿片止痛法之耐藥性發生後，用於控制疼 痛’特別是在癌症病患中。 /系統止痛劑’譬如刪〇與類阿片，係欲與僅可作為局 一止痛劑/麻醉劑使用之治療劑區別。習知局部止痛劑，孽 如利多卡因與賽羅卡因係為非選擇性離子通道阻斷劑，當 系、'先方式投藥時’其可致死。非選擇性納通道阻斷劑之 描述可參閱Μ·，D·等人J廳鳥(2001)，44(2): 128409 -14- 200836743 115-37。 已知數種納通道調制劑作為抗搐㈣或抗”劑使用， 譬如胺f醯氮箪、阿米替林（amitriptyline)、拉莫三金桌 (lamotrigine) A ^ (riiuzole) , ^ ^^ ^ ^ 感性（ttx_s)納通道為標的。此種ττχ·8劑係遭受到限制劑量 副作用，包括眩暈、失調及倦睡’主要是由於對腦中删 通道之作用所致。 於疼痛中之鈉通道角色 納通道在保持正常與病理學狀態上係扮演各式各樣也合 之角色，包括電壓選通納通道在發生異常神經元活性與神 經病原性或病理學疼痛中所扮演之長久以來經認定之角色 伽嗯道等人，心以遂之著^ )。在創傷或疾病之 後、，對末梢神經之傷害’可能會造成㈣通道活性與發展 異常傳入活性之改變，包括自軸索切除傳入與敏化；整感 受傷害體之自發活性之異位排放。此等改變可產生對正常 無害刺激之長持續異常過敏性，或感覺異常。神經病原性 疼痛之實例包括但不限於癌療後神經痛、三叉神經痛、糖 尿病患者之神經病、慢性下方背痛、幻想肢疼痛及癌症與 化子療法所造成之疼痛、慢性骨盆疼痛、複合區域性疼痛 徵候簇及相關神經痛。 在治療神經病原性疼痛徵候上’利用藥療法已有某種程 度之成功’譬如加巴潘亭(—in)，及最近之普瑞加巴林 (pregabalm) ’作為短期第―線治療藥品。但是，對於神經病 原性疼痛之藥療法’ 一般而$，具有有限之成功，對常用 128409 -15- 200836743 疼痛降低藥物’譬如NSAID與阿卿，幾乎無回應。因 此:發掘新穎治療形態，仍然有相當可觀需求。 有有限數目之潛在有效鈉通道阻斷劑在臨床上伴隨著 不利事件。亦有未達到之醫療需求，以有效且未具有 不利田’i作用地治療神經病原性疼痛及其他納通道有關聯之 病理學狀態。本發明係提供化合物，使用方法，及包含此 等化合物之組合物，以符合此等重要需求。 r 相關文獻 PCT公告之專利φ請案w〇㈣7彻$係揭示新賴稠合環 s同基嘧啶衍生化合物。 【發明内容】 本發明係冑對本發明之p奎嗅琳酮與稠合嘯咬銅化合物， 包含該化合物之醫藥組合物，及使用該化合物與組I物以 :台療及/或預防鈉通道所媒介疾，病或症狀(譬如疼痛)之方 法。本發明亦針對本發明之4嗤„林酮與稠合喷 包含該化合物之醫藥組合物，及使用該化合物與組合；^以 t療其他納通道所媒介疾病或症狀之方法，該疾病或症狀 匕括仁不限於中樞神經症狀，譬如癲癇、焦慮、抑繫及兩 二疾病，心血官症狀，譬如節律不齊、心房纖維顫動及心 至纖維顫動；神經肌肉症狀，譬如不安寧腳部徵候装、自 發性震顏及肌肉麻痒或破傷風；抵抗中風之神經保護、青 光眼、神經損傷及多發性硬化；及通道病，譬如肢端紅痛 病與家族性直料痛徵候簇。本發明亦針對本發明之峻嗤 酮/、稠& ώ疋酮化合物，包含該化合物之醫藥組合物， 128409 •16- 200836743 =二化合：與組:物以治療及/或預防㈣ 漆癢广：广症狀言如兩膽固醇血症、良性攝護腺增生、 瘙癢病及癌症。 曰土 因此，於-方面，本發明$針對式①化合物:Non-opioid analgesics, such as acetaminophen, and NSAIDs, can be used in acute and chronic pain due to a variety of causes, including surgery, trauma, inflammation, and cancer. NSAID is required for pain involving inflammation because acetaminophen lacks anti-inflammatory activity. Opioids also lack anti-inflammatory activity. All nsaid inhibit cyclooxygenase (COX), thus inhibiting prostaglandin synthesis and reducing fire! A painful response. There are at least two C〇x isomeric recombinations, cox· and c〇x_2. Commonly used non-selective cox inhibitors include ibuprofen (ibupr〇fen) and naproxen (napr〇xen). COX-lanthanide is found in platelets, (3) tracts, kidneys, and most other human tissues, and its inhibitory line is thought to be associated with adverse effects such as gastrointestinal bleeding. The development of selective COX-2NSAH), such as celecoxib, valdec〇xib and mfecoxib, has the benefit of non-selective Ν Reduce the adverse effects of the intestines and kidneys. However, current evidence suggests that the chronic use of certain selective COX-2 inhibitors may increase the risk of stroke. The benefits of opioids are recommended by the American Society (IV), based on the medical records of pain and the body including repeated pain assessment. As opiates are used in conjunction with opiates, the use of diarrhea and versatile forms of treatment should include diagnosis, integration of interdisciplinary treatment plans, and appropriate current patient monitoring. It is further recommended that opioids should be added to non-opioids to treat acute pain and cancer-related pain that does not return to a single non-opioid. The opioid analgesic is in the central and peripheral gods (four) system, for the M / c type of special - receptor filling activator. Depending on the opioid and its formulation or mode of administration, it may have a shorter or longer duration. All types of money have the risk of causing depression, liver failure, palpation and dependence, and are not ideal for long-term or chronic pain management. ^ Many other drug classes can enhance the role of opioids or NSA][d, have independent analgesic activity in some = or neutralize the side effects of analgesics, regardless of the drug's role, which is commonly referred to as " Total analgesic " tricyclic antidepressants, antiepileptic drugs, local anesthetics, corticosteroids, skeletal muscle relaxants, anticonvulsants, antihistamines, benzodiazepines, coffee, Topical agents (such as capsaicin), dextroamphetamine and flu:: wells, all used clinically, as adjuvant therapy or individually for the treatment of pain. In particular, anti-epileptic drugs have enjoyed a certain degree in the treatment of pain symptoms. # °❹'Gabapentin's 'unidentified treatment' is required for neuropathic pain. Other clinical trials are trying to establish central neuropathic pain in response to ion channel blockade Agent, a gentleman 2 and/or NMDA (N-methyl-D-aspartate) channel blocker. The target is a low-affinity NMDA channel blocker for the treatment of neuropathy Primary pain. The system provides a pre-station electrophysiological note to support the use of NMDA antagonists to treat neuropathic pain. This agent has also been found to be used to control pain after the occurrence of resistance to opioid analgesia. It is in cancer patients. / Systematic analgesics, such as deletions and opioids, are intended to be distinguished from therapeutic agents that can only be used as an analgesic/anesthetic. Conventional topical analgesics, such as lidocaine and competition Rocaine is a non-selective ion channel blocker, which can be lethal when it is administered in a 'first mode'. The description of non-selective nanochannel blockers can be found in J·, D· et al. 2001), 44(2): 128409 -14- 200836743 115-37. Several kinds of nanochannel modulators are known to be used as anti-mite (tetra) or anti-"drugs, such as amines, nitrogen, amitriptyline, Lamorigine A ^ (riiuzole) , ^ ^^ ^ ^ The perceptual (ttx_s) nanochannel is the target. This type of ττχ·8 agent suffers from limited dose side effects, including dizziness, dysregulation, and drowsiness, mainly due to the effect of deleting channels in the brain. The role of the sodium channel in the pain plays a wide variety of roles in maintaining normal and pathological conditions, including voltage-selected passages in abnormal neuronal activity and neuropathogenic or pathological pain. Playing the long-established role of Gambling and others, the heart is stunned ^). After trauma or disease, damage to the peripheral nerves may cause (4) channel activity and development of abnormal afferent activity changes, including axonal resection and sensitization; ectopic discharge of the spontaneous activity of the injured body. These changes can result in long persistent allergic to normal, harmless stimuli, or paresthesia. Examples of neuropathic pain include, but are not limited to, neuralgia after cancer therapy, trigeminal neuralgia, neuropathy in diabetic patients, chronic lower back pain, fantasy limb pain, and pain caused by cancer and proton therapy, chronic pelvic pain, complex area Sexual pain syndrome and related neuralgia. There has been some degree of success in the treatment of neuropathic pain symptoms, such as gabapanting (-in), and more recently pregabalm as a short-term first-line treatment. However, for the treatment of neuropathic pain, the general treatment, with limited success, has almost no response to commonly used 128409 -15-200836743 pain-reducing drugs, such as NSAID and Aqing. Therefore, there is still considerable demand for discovering novel treatment modalities. A limited number of potentially effective sodium channel blockers are clinically associated with adverse events. There are also unmet medical needs to treat neuropathic pain and other pathologically related pathologies in an effective and unfavorable manner. The present invention provides compounds, methods of use, and compositions comprising such compounds to meet these important requirements. r Related Literature PCT Announced Patent φ Request Case w〇 (4) 7 $ $ 揭示 reveals the new lysine ring s synthylpyrimidine derivative compound. SUMMARY OF THE INVENTION The present invention relates to a p-quinolone and a fused copper compound of the present invention, a pharmaceutical composition comprising the same, and the use of the compound and the group I to: treat and/or prevent sodium channel The method of mediating a disease, illness or symptom (such as pain). The present invention is also directed to the pharmaceutical composition of the present invention comprising conjugated ketone and fused spray, and the use of the compound and the combination; the method of treating the disease or symptom of other subchannels by t treatment, the disease or symptom匕 仁 仁 is not limited to central nervous symptoms, such as epilepsy, anxiety, inhibition and two or two diseases, cardiovascular symptoms, such as irregular rhythm, atrial fibrillation and heart to fibrillation; neuromuscular symptoms, such as restless foot signs Spontaneous seizures and muscle itching or tetanus; neuroprotection against stroke, glaucoma, nerve damage and multiple sclerosis; and channel diseases such as limbal red pain and familial rectal pain syndrome. The invention also targets The scorpion ketone/, condensed & oxime ketone compound of the present invention, the pharmaceutical composition comprising the same, 128409 • 16- 200836743 = the second compound: and the group: the substance for treatment and/or prevention (4) itchiness: wide symptoms Such as two cholesterolemia, benign prostate hyperplasia, scrapie and cancer. Therefore, in terms of, the present invention is directed to the compound of formula 1:

其中： n為1至4 ; Q、. 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烧基、烯基、快基、幽基、齒烧 基齒烯基、函炔基、環烷基、環燒基烷基、環烷基 烯基、裱烷基炔基、芳基'芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 专基、雜务烧基、雜芳基烯基、雜芳基炔基、_r6_Cn、 -R6-N〇2、-R6-OR5、_R6_N(R4)R5、_R6-S(〇)pR4、_r6 _c(〇)r4、 -R -C(S)R4、-R6 -C(R4 )2 C(0)R5、-R6 -C(0)0R4、-R6 -〇c(〇)R4、 -R6-C(S)OR4、-R6-C(0)N(R4)R5、_R6_c(s)n(r4)r5、r6_n(r5> C(0)R4 - .r6 -N(R5 )C(S)R4 - -R6 -N(R5 )C(0)OR4 - -R6 -N(R5 )C(S> 〇R4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)C(S)N(R4)R5、 -R6-N(R5)S(0)tR4、-R6-N(R5)S(0)tN(R4)R5、-R6_S(0)tN(R4)R5、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 -N(R5 )C(N=C(R4 )R5 )N(R4 )R5， 其中各p係獨立為0, 1或2，且各t係獨立為1或2 ; 128409 -17- 200836743 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 务基’而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、_烷基、鹵烯基、_炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烷基、烯基、炔基、鹵烷基、_烯基、齒炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 块基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烧基、雜環基烯基、雜環基炔基、雜芳基、雜芳 燒基、雜芳基烯基、雜芳基炔基、-R7-N(R4)R5或 -R7-N(R4)C(0)0R4 ； 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環 基烧基、雜環基烯基、雜環基炔基、雜芳基、雜 芳烧基、雜芳基浠基或雜芳基炔基可視情況被一 或多個取代基取代，取代基選自包括烷基、烯基、 炔基、1¾基、_烧基、_稀基、_炔基、視情況 經取代之環烷基、視情況經取代之環烷基烷基、 視情況經取代之環烧基稀基、視情況經取代之環 烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取 128409 -18· 200836743 代之芳炔基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜環基烯基、 視情況經取代之雜環基炔基、視情況經取代之雜 芳基、視情況經取代之雜芳烷基、視情況經取代 之雜芳基烯基、視情況經取代之雜芳基炔基、 -R6，CN、-R6-N〇2、_r6_or5、-r6-〇c(o)r4、-R6-〇S(0)2R4 、-R6 -C(0)R4、_R6 -C(0)0R4、_r6 -C(0)N(R4 )R5、Wherein: n is 1 to 4; Q, is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, fast radical, leucoyl, dentate alkenyl , alkynyl, cycloalkyl, cycloalkyl, cycloalkylalkenyl, nonylalkynyl, aryl 'aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocycloalkane , heterocyclylalkenyl, heterocyclylalkynyl, heterocyclyl, oxaring, heteroarylalkenyl, heteroarylalkynyl, _r6_Cn, -R6-N〇2, -R6-OR5, _R6_N (R4) R5, _R6-S(〇)pR4, _r6 _c(〇)r4, -R -C(S)R4, -R6 -C(R4 )2 C(0)R5, -R6 -C(0) 0R4, -R6 -〇c(〇)R4, -R6-C(S)OR4, -R6-C(0)N(R4)R5, _R6_c(s)n(r4)r5, r6_n(r5> C( 0) R4 - .r6 -N(R5 )C(S)R4 - -R6 -N(R5 )C(0)OR4 - -R6 -N(R5 )C(S> 〇R4, -R6-N(R5 C(0)N(R4)R5, -R6-N(R5)C(S)N(R4)R5, -R6-N(R5)S(0)tR4, -R6-N(R5)S( 0) tN(R4)R5, -R6_S(0)tN(R4)R5, -R6 -N(R5)C(=NR5)N(R4)R5 and -R6 -N(R5)C(N=C( R4)R5)N(R4)R5, wherein each p-line is independently 0, 1 or 2, and each t-series is independently 1 or 2; 128409 -17-200836743 or two adjacent R1 groups and their direct even Together with a carbon or heterocyclic atom, a fused ring may be formed, selected from a cycloalkyl, aryl, heterocyclic or hydroxy group, and the remaining R1 groups, if present, are as described above; R2 is hydrogen, alkane Base, alkenyl, alkynyl, _alkyl, haloalkenyl, ynkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aralkenyl, arylalkynyl , heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is hydrogen, alkyl , alkenyl, alkynyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkyl block, aryl, aralkyl Alkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroaryl Alkynyl, -R7-N(R4)R5 or -R7-N(R4)C(0)0R4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl , aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl A heteroaryl, heteroarylalkyl, heteroarylalkyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, 1,4-yl, _ , 稀, _ alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl alkyne Or an optionally substituted aryl group, optionally substituted aralkyl group, optionally substituted aralkenyl group, optionally taken as an aromatic alkynyl group, optionally substituted, as described in 128409 -18. Substituent, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted Aralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6,CN, -R6-N〇2, _r6_or5, -r6-〇c(o)r4, -R6-〇S(0)2R4, -R6 -C(0)R4, _R6 -C(0)0R4, _r6 -C(0)N(R4)R5,

-R6-N(R4)R5、_r6_n(R5)c(〇)R4、-R6_n(r5)c(〇)〇R4、 -R6-N(R5)C(〇)N(R4)R5 、 -R6 -N(R5 )S(0)t R4 、 -R6-N[S(〇)tR4]2 、 -R6 «N(R5 )C(=NR5 )N(R4 )R5 、 -R6-N(R5)c(=NR5)N(R4)CN、-R6-N(R5)c[=NC(0)0R4]-N(R4 )-C(〇)〇R4、-R6 _n(R5 )-R7 -N(R4 )R5、_n=C(OR4 )R5 、-R6-N=C(R4)R5、-R6-N(R5)_R6-〇r5、_R6_s(〇)pR4 及 -S(〇)tN(R4 )R5，其中各p係獨立為〇, i或2，且各 t係獨立為1或2 ;-R6-N(R4)R5, _r6_n(R5)c(〇)R4, -R6_n(r5)c(〇)〇R4, -R6-N(R5)C(〇)N(R4)R5, -R6 -N(R5 )S(0)t R4 , -R6-N[S(〇)tR4]2 , -R6 «N(R5 )C(=NR5 )N(R4 )R5 , -R6-N(R5) c(=NR5)N(R4)CN, -R6-N(R5)c[=NC(0)0R4]-N(R4)-C(〇)〇R4, -R6 _n(R5 )-R7 -N (R4) R5, _n=C(OR4)R5, -R6-N=C(R4)R5, -R6-N(R5)_R6-〇r5, _R6_s(〇)pR4 and -S(〇)tN(R4 R5, wherein each p is independently 〇, i or 2, and each t is independently 1 or 2;

各R4與R5係獨立選自包括氫、烷基、烯基、炔基、.烷基、 t烷基、烷氧烷基、視情況經取代之環烷基、視情況 I取代之環烷基烷基、視情況經取代之芳基、視情況 I取代之芳烧基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 之 〆 :口彼兩者所連接之氮一起，形成視情況經取代 6、雜娘基或視情況經取代之N-雜芳基； 為直接鍵結、視情況經取代之直鏈或分枝狀次烧基 128409 -19- 200836743 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鍵或分枝狀次快基鍵；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈； 為其立體異構物、對掌異構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 於另一方面，本發明係提供醫藥組合物，其包含藥學上 可接受之賦形劑，與治療上有效量之如上述之式⑴化合物， 為其立體異構物、對掌異構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 於另一方面，本發明係提供下式屮丨）化合物：Each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkyl, talkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl. Alkyl, optionally substituted aryl, optionally substituted aryl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heteroaryl and a substituted heteroaralkyl group; the hydrazine: the nitrogen to which the two are attached, together with the N-heteroaryl group which is optionally substituted, substituted or optionally substituted; A linear or branched sub-alkyl group substituted in the case of 128409 -19- 200836743 chain, optionally substituted linear or branched sub-alkenyl chain or optionally substituted straight or branched sub-fast base a bond; and R7 is a linear or branched alkylene chain, a linear or branched subalkenyl chain or a linear or branched subalkynyl chain; a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient, and a therapeutically effective amount of a compound of formula (1) as described above, which are stereoisomers, palmomerisomers, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention provides a compound of the formula:

μ即2-丁基-3-[4-(四氫吡咯基胺基）苯基]p奎唑啉_4(3H)_酮， 為其立體異構物、對掌異 或其藥學上可接受之鹽、 對掌異構物、互變異構物或其混合物； 之鹽、溶劑合物或前體藥物。 有效量之如上述之式（M)化合物 異構物、互變異爐铷沈甘、、曰人^ 於另方面，本發明係提供醫藥組合物，其包含治療上 *合物，為其立體異構物、對掌 合物，或其藥學上可接受之鹽、 或多種藥學上可接受之賦形劑。 卜明係關於一種醫藥組合物，其 可接受之賦形劑中，且當被投 吳構物、互變異構物或其混合物，或其秦 溶劑合物或前體藥物，及一或多種藥學-於-項具體實施例+，本發明係關於一 包含式（M)化合物在藥學上可接受之 128409 -20- 200836743 予動物，較佳為,乳動物，最佳 療與疼痛有關聯之疾病或症狀。其量可有效治 改本發明係提供在哺乳動物中治療、預防或 之方法’該—選自包括疼痛、抑 皇中此//呼吸道疾病及精神病學疾病，及其組合， 中b方法係包括對有需 之如口 h 動物投^治療上有效量 互變显：物物’為其立體異構物、對掌異構物、 f. i 物SUL物’或其藥學上可接受之鹽、溶劑合 1=樂；，或一種醫藥組合物，其包含如上述之本發 盆、^物\體異構物、對掌異構物、互變異構物或 二=其藥學上可接受之鹽、溶劑合物或前體藥物， 及柰學上可接受之賦形劑。 於另一方面，本發明係提供在哺 u ^動物較佳為人類中治 =二:旦 法係包括對有需要之哺乳動物投 對掌：構物放里t如上逃本發明化合物，為其立體異構物、 對I、構物、互異構物或其混合物；或其藥學上可接受 之鹽 ' 溶劑合物或前體藥物’或—種醫藥叙合物，其包含 :::::發明化合物’為其立體異構物、對掌異構物： 互^構物或其混合物；或其藥學上可接受之鹽、溶劑合 物或刚體樂物，及藥學上可接受之賦形劑。 於另-方面’本發明係提供一種在哺乳動物中治 輕疾病、症狀或病症嚴重性之方法，其中__或多種恤^ Nav 1,, Nav 1.3, Nav 1.4, Nav Nav ,6, Nay ,, ^ χ g ^ ^ 2 活化作用或活動過度係牵連該疾病、症狀或病症，发中此 128409 -21 - 200836743 包括對有需要之哺乳動物投予治療上有效量之如上 “ 1明化合物’為其立體異構物、對掌異構物、互變里 構物或其混合物；或其藥學 ” 體藥物，或-種醫单袓入* “人 “勿戈月】 面i 组合物，其包含如上述之本發明化合 :〜、，體異構物、對掌異構物、互變異構物或其混合 ’或其樂學上可接受之鹽、溶劑合物或前體藥物，及筚 學上可接受之賦形劑。 杂 r 、於另一方面’本發明係提供在哺乳動物中治療一範圍鈉 通道所媒介疾病或症狀之方法，該疾病或症狀例如愈聊 有關聯之疼痛、贈治療利致之神經病、三又神經痛、 厂包療後神經痛、正常疼痛、熱敏感性、局部肉狀瘤病、刺 激性腸徵候蔟、券隊& 、克隆氏病、與多發性硬化（MS)有關聯之疼 痛、_肌萎縮性側索硬化（ALS)、糖尿病患者之神經病、末梢 神-病、關即炎、風濕性關節炎、骨關節炎、動脈粥瘤硬 化、陣發性肌緊張不足 張不足肌無力徵候簇、肌強直、亞性言 熱、膽囊纖維變性、㈣固酮過多症、橫紋肌溶解:甲: ㈣能減退症、兩極抑繫、焦慮、精神分裂症、納通道毒 素相關疾病、家族性肢端紅痛病、原發性肢端紅痛病、家 族性直腸疼痛、癌症、癲癎、部份與一般緊張發作、不安 寧腳部徵候簇、節律不齊、纖維肌痛、在因中風所造成之 絕企狀態下之神經保護、青光眼或神經損傷、快速節律不 齊、心房纖維顫動及心室纖維顫動，其中此方法係包括對 有而要之甫礼動物’較佳為人類，投予治療上有效量之如 上述本毛明化合物’為其立體異構物、對掌異構物、互變 128409 -22- 200836743 異構物或其混合物，.宜風 梁予上可接受之鹽、溶劑合物或 別體梁物’或一蘇較姑/ . 西，、、、且口物，其包含如上述之本發明化 5物，為其立體異構物、 合物·，或其藥學上可接構物、錢異構物或其混 ’、 又之鹽、溶劑合物或前體藥物，及 樂學上可接受之賦形劑。 一；、方面’本發明係提供在哺乳動物較佳為人類中， 經由在哺乳動物中抑制 p制離子通置經過電壓依賴性鈉通道， f 以治療一範圍鈉通道所媒介疾病或症狀之方法，其中此方 法係包括對有需要之哺乳動物投予治療上有效量之如上述 本毛月化。物’為其立體異構物、對掌異構物、互變異構 物或其混合物，或直藥風， — 、 ，、柰予上可接受之鹽、溶劑合物或前體μ is 2-butyl-3-[4-(tetrahydropyrrolylamino)phenyl]p- quinazoline-4(3H)-one, which is a stereoisomer, palm or pharmaceutically acceptable Accepted salts, palmier isomers, tautomers or mixtures thereof; salts, solvates or prodrugs. An effective amount of the compound (M) isomer, a mutual variability, a stagnation, and the like. In another aspect, the present invention provides a pharmaceutical composition comprising a therapeutic composition, A construct, a compound of the formula, or a pharmaceutically acceptable salt thereof, or a plurality of pharmaceutically acceptable excipients.卜明 relates to a pharmaceutical composition, which is acceptable for use in an excipient, and when administered as a constitutive construct, tautomer or mixture thereof, or a homolog thereof or a prodrug thereof, and one or more pharmaceuticals - In the specific embodiment +, the present invention relates to a compound comprising the compound of the formula (M) in a pharmaceutically acceptable 128409 -20-200836743 to an animal, preferably a milk animal, for optimal treatment of pain-related diseases Or symptoms. The method of the present invention is to provide a method for treating, preventing or treating in a mammal, which is selected from the group consisting of pain, depression, respiratory diseases and psychiatric diseases, and combinations thereof, and the method b includes For therapeutic purposes, the therapeutically effective amount of each other is: the substance 'is its stereoisomer, palmar isomer, f. i SUL' or its pharmaceutically acceptable salt, Solvent 1 = music; or a pharmaceutical composition comprising the above-mentioned hair pot, substance / body isomer, palmar isomer, tautomer or two = pharmaceutically acceptable salt thereof , solvates or prodrugs, and excipients that are scientifically acceptable. In another aspect, the present invention provides that the animal is preferably treated in humans. The second method includes the administration of a mammal to a mammal in need thereof: a stereoisomer, a pair I, a construct, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, a solvate or a prodrug or a pharmaceutical composition comprising:::: The compound of the invention 'is a stereoisomer, a palmomer: an intertwiner or a mixture thereof; or a pharmaceutically acceptable salt, solvate or a rigid body, and a pharmaceutically acceptable compound Shape agent. In a further aspect, the invention provides a method of treating the severity of a mild disease, symptom or condition in a mammal, wherein __ or a variety of ^ 1, Nav 1.3, Nav 1.4, Nav Nav, 6, Nay, , ^ χ g ^ ^ 2 activation or hyperactivity is implicated in the disease, symptom or condition, in which 128409-21-200836743 comprises administering to a mammal in need thereof a therapeutically effective amount of the above "1 compound" a stereoisomer, a palmomer, a tautomeric constitutive or a mixture thereof; or a pharmaceutically acceptable drug thereof, or a medicinal remedy; The invention of the invention as described above: ~,, an isomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a dropout Acceptable excipients. In another aspect, the present invention provides a method of treating a disease or condition mediated by a range of sodium channels in a mammal, such as a pain associated with a more painful treatment, a neurosis of a therapeutic benefit, and a third Neuralgia, post-constrained neuralgia, normal pain, heat sensitivity, local sarcoidosis, irritating bowel symptoms, vouchers & cloning, schistosomiasis, pain associated with multiple sclerosis (MS), _ amyotrophic lateral sclerosis (ALS), neuropathy in diabetic patients, peripheral dementia, dying, rheumatoid arthritis, osteoarthritis, atherosclerosis, paroxysmal dystonia Cluster, myotonia, sub-sexual heat, gallbladder fibrosis, (4) ketosis, rhabdomyolysis: A: (4) hypothyroidism, bipolar inhibition, anxiety, schizophrenia, nanochannel toxin-related diseases, familial extremities Red pain, primary acral red pain, familial rectal pain, cancer, epilepsy, partial and general tension, restless foot syndrome, irregular rhythm, fibromyalgia, caused by stroke It Neuroprotection, glaucoma or nerve damage, arrhythmia, atrial fibrillation, and ventricular fibrillation in a state of absolute state, including the treatment of a sacred animal, preferably a human, for therapeutic benefit. The amount of the present invention is as follows: its stereoisomer, palmar isomer, interconversion 128409 -22-200836743 isomer or mixture thereof, Yifengliang, acceptable salt, solvate Or a spheroidal material or a sulphate, or a sulphate, which comprises the above-described chemical substance 5, a stereoisomer thereof, or a pharmaceutically acceptable substance thereof. A construct, a money isomer or a mixture thereof, a salt, a solvate or a prodrug, and a pharmaceutically acceptable excipient. The invention provides a method for treating a disease or a symptom of a range of sodium channels in a mammal, preferably a human, by inhibiting p-ion ion transduction through a voltage-dependent sodium channel in a mammal. Wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount as described above. The substance 'is a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a straight drug, a salt, a solvate or a precursor.

藥物’或一種醫攀矣日人& ^ > A 、 ’、、、、D物，其包含如上述之本發明化合物， 為八立體異構物、對掌異構物'互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物，及藥學上 可接受之賦形劑。 、於另—方面’本發明係提供在哺乳動物較佳為人類中， 治療或預防高膽固醇血斥 , f 呷症之方法，其中此方法係包括對有 需要之哺乳動物投予治療上有效量之如上述本發明化合 物’為其立體異構物、對f異構物、互變異構物或其混合 物’或其藥學上可接受之鹽、溶劑合物或前體藥物，或一 種醫藥組合物，苴句冬‘ μ、七—丄外 ，、匕3如上述之本發明化合物，為其立體 異構物、肖掌異構物、互變異構物或其混合物，·或其藥學 上可接受之鹽、溶劑合物或前體藥物，及藥學上可接受之 賦形劑。 128409 -23- 200836743 、；方面本發明係提供在哺乳動物較佳為人類中， 治療或預防良性攝護腺 、 亡+亦 9生之方法，其中此方法係包括對 有要之哺乳動物投予Λ s 于/σ療上有效i之如上述本發明化合 〜、亡體異構物、對掌異構物、互變異構物或其混合 j/、藥予上可接受之鹽、溶劑合物或前體藥物，或一 種醫藥組合物，並包含如 ^ ，、匕3如上述之本發明化合物，為其立體 ”構物、對掌異構物、互變異構物或其混合物；或盆率學 r" 上可接受之鹽、溶劑合物或前體藥物，及藥學 2 賦形劑。 饮又< 、於另方面，本發明係提供在哺乳動物較佳為人類中， 治療或預防瘙癢病之方法，#中此方法係包括對 哺乳動物投予#、磨卜古μ旦 t I之 口療上有效ϊ之如上述本發明化合物， :體異構物、對掌異構物、互變異構物或其混合物，或立 樂學上可接受之鹽、溶劑合物或前體藥物，或一種醫藥組 合物’其包含如上述之本發明化合物，為其立體 對掌異構物、互變異構物或其混合物；或其藥學上可接受 之鹽、：劑合物或前體藥物’及藥學上可接受之賦形劑？ ; 方面，本發明係提供在哺乳動物較佳為人類 治療或預防癌症之方法，其中此方法係包括 要 乳動物投予治療上有效量之如上述本發明化合物而= ，再物對旱異構物、互變異構物或其混合物，或1 學上可接受之鹽、溶劑合物或前體藥物，或一種d 物，甘裡商樂組合 八匕3如上述之本發明化合物，為其立體異構物、掛 掌異構物、互變異構物或其混合物；或其藥學 σΓ接受之 128409 -24- 200836743 鹽、溶劑合物或前體藥物，及藥學上可接受之賦形劑。 於另-方面’本發明係提供醫藥療法，且併用一或多種 其他本發明化合物或-或多種其他已接受之療法，或作為 其：何組合以增加現有或未來藥物療法之功效，或降低伴 隨者已接受療法之不利事件。於—項具體實施例中，本發 明係關於將本發明化合物與已確立或未來療法結合之醫藥 組合物，供本發明中所列示之適應徵用。 於另方©，本發明係針對如上述之本發明化合物，為 其立體異構物、對掌異構物、互變異構物或其混合物，或 其藥學上可接受之鹽、溶劑合物或前體藥物，或一種醫藥 組合物包含藥學上可接受之賦形劑與如上述之本發明 化合物，為其立體異構物、對掌異構物、互 ^ 混…其藥學上可接受之鹽、溶劑合物或前=? 於藥劑製備上之用it ’該藥劑係在哺乳動物中治療納通道 所媒介之疾病或症狀。 發明詳述 定義 本文中指稱之某些化學基團係以簡寫符號置於前，指示 欲在所指示化學基围中發現之碳原子總數。例如，c7_Cu 烷基係描述如下文定義之烷基，具有總共7至12個碳原子丨: 而q-Cu%烷基烷基係描述如下文定義之環烷基烷基，具 有總共4至12個碳原子。於簡寫符號中之碳總數並不包含可 能存在於所描述基團之取代基中之碳。 除了前述以外，當使用於本專利說明書與隨文所附請求 128409 -25· 200836743 項中時’除非有相反之指定 意義： 否則下列術語具有所指示之 胺基η係指_νη2基團。 氰基”係指-CN基團。 經基係指-ΟΗ基團。 亞胺基’’係指=ΝΗ取代基。 硝基’’係指-Ν02基團。A drug, or a medical compound, & ^ > A , ', , , D, which comprises a compound of the invention as described above, which is an eight stereoisomer, a palmomer isomer 'tautomer Or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable excipient. In another aspect, the present invention provides a method for treating or preventing hypercholesterolemia, f snoring in a mammal, preferably a human, wherein the method comprises administering a therapeutically effective amount to a mammal in need thereof. The compound of the present invention as described above is a stereoisomer, a p-isomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition , 苴冬冬' μ, 七-丄,, 匕3, as described above, a compound of the invention, which is a stereoisomer, a palmo isomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable compound thereof a salt, solvate or prodrug, and a pharmaceutically acceptable excipient. 128409 -23- 200836743, aspects of the present invention provide a method for treating or preventing benign prostate, dying, and genital in a mammal, preferably a human, wherein the method comprises administering to a mammal in need thereof Λ s / σ therapeutically effective i, as described above, the compound of the present invention, the apoisomer, the palmomer, the tautomer or a mixture thereof, the acceptable salt or solvate Or a prodrug, or a pharmaceutical composition, and comprising a compound of the invention as described above, as a stereostructure, a palmomer, a tautomer or a mixture thereof; or a pot ratio An acceptable salt, solvate or prodrug, and a pharmaceutical 2 excipient. Drinking < In another aspect, the present invention provides for treating or preventing itching in a mammal, preferably a human. The method of the disease, the method of the invention includes the administration of the mammal, the antibacterial treatment of the compound of the invention, the above-mentioned compound of the invention, the isomer, the palm isomer, the mutual An isomer or a mixture thereof, or a salt or a solvate Or a prodrug, or a pharmaceutical composition comprising a compound of the invention as described above as a stereoisomer, tautomer or mixture thereof; or a pharmaceutically acceptable salt thereof, a composition thereof Or a prodrug' and a pharmaceutically acceptable excipient? In terms of the present invention, the present invention provides a method of treating or preventing cancer in a mammal, preferably a human, wherein the method comprises administering a therapeutically effective amount to the mammal. Such as the above-mentioned compound of the present invention =, a reciprocal isomer, tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug, or a d, Gan Lishang乐组合八匕3 The compound of the present invention as described above, which is a stereoisomer, a palmo-isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, 128409 -24-200836743 salt, solvate or Prodrugs, and pharmaceutically acceptable excipients. In another aspect, the invention provides a medical therapy, and in combination with one or more other compounds of the invention or - or a plurality of other accepted therapies, or as Combine Adding the efficacy of existing or future drug therapies, or reducing the adverse events that the accompanying person has received the therapy. In a particular embodiment, the invention relates to a pharmaceutical composition that combines a compound of the invention with established or future therapies for the present invention. The invention as set forth in the Invention. The present invention is directed to a compound of the invention as described above, which is a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutical thereof. An acceptable salt, solvate or prodrug, or a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the invention as described above, which are stereoisomers, palmomers, and Mixing with a pharmaceutically acceptable salt, solvate or pre-agent for the preparation of a medicament which is used to treat a disease or condition mediated by the nanochannel in a mammal. DETAILED DESCRIPTION OF THE INVENTION Definitions Certain chemical groups referred to herein are preceded by a shorthand notation indicating the total number of carbon atoms to be found in the indicated chemical footprint. For example, the c7_Cu alkyl group describes an alkyl group as defined below having a total of 7 to 12 carbon atoms quinone: and the q-Cu% alkylalkyl group describes a cycloalkylalkyl group as defined below, having a total of 4 to 12 One carbon atom. The total number of carbons in the abbreviated symbols does not include carbon which may be present in the substituents of the groups described. In addition to the foregoing, when used in this patent specification and in the accompanying claims, the disclosure of which is incorporated herein by reference in its entirety, the entire disclosure of the disclosure of the disclosures of "Cyano" refers to a -CN group. The radical refers to a fluorenyl group. The imine group '' refers to a hydrazine substituent. The nitro'' refers to a - 02 group.

ί 酉同基係指=0取代基。 硫酮基π係指=s取代基。 三氟甲基”係指-CF3基團。 烷基"係指直鏈或分枝狀烴鏈基團，僅由碳與氫原子組 成’未含有+飽和性，具有一至十二個碳原？ ’較佳為一 至八個碳原子或—至六個碳原子，且其係藉由單鍵連接至 分子之其餘部份’例如甲基、乙基、正.丙基、^甲基乙基（里 丙基）、正·丁基、正-戊基、U_二甲基乙基（第三丁基）、3_ 甲基己基、2-甲基己基等。除非本專利說明書中另有明確 述及’否則燒基可視情況被下列基團之一取代：炫基、烯 基、函基、_烯基、氰基、硝基、芳基、環烧基、雜環基、 雜芳基、酮基、三甲基料基、備"、卿)_r1 4、_n(ri 4 )2、 -C(〇)R- ^ -C(〇)〇Rl4 , .C(0)N(r14)2 ^ _N(r14)c(〇)〇r16 ^ -N(R-)C(0)R16 , -N(RI4)S(〇)tRl6(^ t 2 _s(〇)t〇Rl6(^ 中t為1至2)、_S(〇)pRl6(其中P為〇至2)及-S_(R“)2(其中t =至2)，其中各R"係獨立為氯、炫基、幽炫基、環燒基、 %烷基烷基、芳基、芳烷基、雜環基、雜環基烷基、雜芳 128409 -26 - 200836743 基或雜芳烷基；且各R1 6為烷基、_烷基、環烷基、環烷基 烷基、芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜 芳烧基。 烯基’’係指直鏈或分枝狀烴鏈基團，僅由碳與氫原子組 成，含有至少一個雙鍵，具有二至十二個碳原子，較佳為 一至八個碳原子，且其係藉由單鍵連接至分子之其餘部份， r 例如乙烯基、丙+烯基、丁小烯基、戊小烯基、戊_丨冷二烯 基等。除非本專利說明書中另有明確述及，否則烯基可視 情況被下列基團之一取代：烷基、烯基、_基、_烯基、 氰基、硝基、芳基'環烷基、雜環基、雜芳基、酮基、三 、-C(〇)Rl 甲基矽烷基、-OR1 C(0)0R、_C(0)N(R14)2、-N(R14)C(0)0R16、_n(R14)C(〇)R16、 -N(R“剛tRl6(其中 t 為 i 至 2)、_s(〇)t〇Rl6(其中 t 為 i 至 2)、 S(〇)pRl 6 (其中P為0至2)及-.難14 )2 (其中t為1至2)，其中 各R14係獨立為氫、烷基、鹵烷基、環烷基、環烷基烷基、 芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基； 各R為烧基、鹵烧基、環烧基、環烧基烧基、芳基、芳 燒基、雜環基、雜環基院基、雜芳基或雜芳烧基。 "炔基”係指直鏈或分枝狀煙鏈基團，僅由碳與氫原子組 成’含有至少-個參鍵，視情況含有至少—個雙鍵，具有 :至十二個碳原子，較佳為二至人個碳原子，且其係藉由 早鍵連接至分子之其餘部份，例如乙块基、㈣基、丁块 ，、戍块基、己快基等。除非本專利說明書中另有明確述 及，否則块基可視情況被-或多個下列取代基取代：烧基、 128409 -27- 200836743 稀基、㈣、i烯基、氰基、石肖基、芳基、㈣基、雜環 基、雜芳基、酮基、三甲基石夕院基、_〇r14、〇c(〇)-r14、 -N(R-)2 . .C(〇)〇Ru . .C(〇)N(r14)2 ^ _N(r14)c(〇)〇r16 ^ -N(R-)C(0)R-. -N(R-)S(0)tRU(^ t t4 t £2) ^ _s(〇)t〇Rl6(^ 中 t 為 1 至 2)、-S(0)PR 6(其中 p為 〇 至2)及 _s(〇)tN(Rl 4 )2 (其中 t 為1至2)，其中各Rl4係獨立為氫、烧基、^基、環烧基、 環烷基烷基、芳基、芳烷基、雜環基、雜環基烷基、雜芳 基或雜芳烧為院基、^烧基、環烧基、環烧基 烷基、芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜 芳烷基。 次烷基或’’次烷基鏈’’係指直鏈或分枝狀二價烴鏈，連 結分子之其餘部份至基團，僅由碳與氫組成，未含有不飽 和性，且具有一至十二個碳原子，例如亞曱基、次乙基、 次丙基、正-次丁基等。次烷基鏈係經過單鍵連接至分子之 其餘部份’及經過單鍵至該基團。次烧基鏈對分子其餘部 伤及對該基團之連接點可經過鏈内之一個碳或任兩個碳。 除非本專利說明書中另有明確述及，否則次烷基鏈可視情 況被下列基團之一取代：烷基、烯基、鹵基、_烯基、氰 基、頌基、方基、ί衣烧基、雜ί哀基、雜芳基、明基、三甲 基矽烷基、-OR14、-OCXOHl14、-NCR14 )2、-C(0)R14、-C(〇)〇Ri 4、 ^(Ο)Ν(Κ14 )2 ^ -NCR1 4 )C(0)0R1 6 ^ -NCR1 4 )C(0)R1 6 > ^(R1 4 )S(0)t ^ (其中 t為 1 至2)、-S(0)t0R16(其中 t為 1 至2)、-S(0)pRi6(其中 p 為〇至2)及-S(0)tN(R14)2(其中t為1至2)，其中各Ri4係獨立為 氣、烧基、_烧基、環烧基、環烧基烧基、芳基、芳烧基、 128409 -28 - 200836743 雜環基、雜環基烷基、雜芳基或雜芳烷基；且各Rl0為烷基、 鹵院基、環烧基、環燒基烷基、芳基、芳烧基、雜環基、 雜環基燒基、雜芳基或雜芳燒基。 ”次烯基”與”次烯基鏈”係指直鏈或分枝狀二價烴鏈，連 結分子之其餘部份至基團，僅由碳與氫組成，含有至少一 個雙鍵，且具有二至十二個碳原子，例如次乙烯基、次丙 烯基、正-次丁烯基等。次烯基鏈係經過單鍵連接至分子之 其餘部份，及經過雙鍵或單鍵至該基團。次烯基鏈對分子 之其餘部份及對該基團之連接點，可經過鏈内之一個碳或 任兩個碳。除非本專利說明書中另有明確述及，否則次烯 基鏈可視情況被下列基團之一取代··烷基、烯基、^基、 鹵烯基、氰基、硝基、芳基、環烷基、雜環基、雜芳基、 酮基、三甲基矽烷基、_〇Rl 4、_〇c⑼·Rl 4、_n(r1 4 )2、_c(〇)r1 4、 -C(0)0R14 . -C(0)N(R14)2 . -N(R14)C(0)0R16 ^ ^(R14 )0(〇)^6 ^ •N(R14)S(〇)tRi6(其中 t 為 i 至 2)、_s(〇)t〇Rl6(其中 t 為【至 、 -S(〇)pR16(其中p為〇至2)及_s(〇XN(Rl4)2(其中t為i至2)，其中 各R係獨立為氫、烷基、鹵烷基、環烷基、環烷基烷基、 芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基； 且各R為烷基、！I[烷基、環烷基、環烷基烷基、芳基、芳 烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基。 ’’次炔基”或”次炔基鏈”係指直鏈或分枝狀二價烴鏈，連 、、、°刀子之其餘部份至基團，僅由碳與氫所組成，含有至少 一個參鍵，且具有二至十二個碳原子，例如次丙炔基、正_ 人丁快基專。次炔基鏈係經過單鍵連接至分子之其餘部 128409 -29- 200836743 且、、二過雙鍵或單鍵至該基團。次炔基鏈對分子之其餘 IM刀及對孩基團之連接點，可經過鏈内之一個碳或任兩個 石反。除非本專利說明書中另有明確述及，否則次炔基鏈可 視情況被下列基團之—取代··燒基、稀基4基、㈣基、 鼠基、硝基、芳基、環烷基、雜環基、雜芳基、酮基、三 甲基矽烷基、-〇Rl4、·〇(：：(〇>]^14、-N(Rl4)2、_c(〇)rM、 -C(0)〇R^ . -C(0)N(R14)2 . -N(R14)C(0)0R16 . -N(R^)C(0)R16 . -N(Rl4)S(〇)tRl6(其中 t 為 1 至 2)、-S(0)t〇Ri6(其中 t 為 i 至 2)、 •S(〇)pR16(其中p為0至2)及_8(〇)_14)2(其中…至幻，其中 各H1”立為氫、燒基、齒烧基、環烧基、環燒基烧基、 芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基； 且各R16為烷基、鹵&基、環烷基、冑烷基烷基、芳基、芳 烧基、雜環基、雜環基烧基、雜芳基或雜芳燒基。 一烷氧基係私式_〇Ra基團，其中Ra為如上文定義之烷基， 含有一至十二個碳原子。烷氧基之烷基部份可視情況如上 文關於燒基所定義經取代。 ’’烷氧烷基”係指式_Rb-〇_Ra基團，其中化為如上文定義之 次烷基鏈，且Ra為如上文定義之烷基。氧原子可結合至次 燒基鏈與烧基巾之任何碳。烧㈣基之録部份可視情況 如上文關於烧基所定義經取代。⑥氧絲之次烧基鍵部份 可視情況如上文關於次烷基鏈所定義經取代。 芳基係私烴裱系統基團，包含氫、6至18個碳原子及 至少一個芳族環。對本發明之目的而言，芳基可為單環狀、 雙環狀、三環狀或四環狀環系統，其可包括經稠合或橋接 128409 -30 - 200836743 之環系統。芳基包括但不限於衍生自苊烯蒽、苊烯茶、苊 烯菲、蒽、奠、苯、鑌、苐、as_茚莘、s_茚莘、氫茚、茚、 莕、蔽、菲、月号、薇及苯并菲之芳基。除非本專利說明書 中另有明確述及，否則"芳基”一詞或字首"芳_”（譬如在 ”芳烧基”中）係意謂包括芳基’視情況被—或多個取代基取 代’取代基獨立選自包括烷基、烯基、.基、^烷基鹵 烯基、氰基、硝基、芳基、雜芳基、雜芳烷基、_R" _〇Rl 4、 -R15_0C(0)-R"、-R15_N(Rl4)2、_r15_c(〇)r14、_r15 _c(〇)〇r14 -R15-C(0)N(R14)2、-R15-N(R14)C(0)0R16、-r15_n(ri4)c(〇)r16、 -R15-N(R14)S(0)tR16(其中t為1至2)…Rl5_N=c(ORl4)Rl4、 -Ri 5-S(0)t OR“（其中 t 為 i 至 2)、-Rl 5 ·8(〇)ρ R1 6 (其中 p 為 〇 至幻 及-R15-S(0)tN(R14)2 (其中t為1至2)，其中各Rm係獨立為氫、 烷基、鹵烧基、環烧基、環烧基烷基、芳基、芳燒基、雜 環基、雜環基烷基、雜芳基或雜芳烷基；各Rl 5係獨立為直 接鍵結或直鍵或分枝狀次烧基或次晞基鍵；且各Rl 6為院 基、iS烷基、環烷基、環烷基烷基、芳基、芳烧基、雜環 基、雜環基烷基、雜芳基或雜芳烷基。 π芳烧基’’係指式-Rb -Rc基團，其中Rb為如上文定義之次烧 基鏈，且Re為如上文定義之一或多個芳基，例如；基、二 本甲基專。方烧基之次烧基鍵部份可視情況如上文關於次 烷基鏈所述經取代。芳烷基之芳基部份可視情況如上文關 於芳基所述經取代。 "芳烯基”係指式-RcrRc基團，其中Rd為如上文定義之次稀 基鏈，且Rc為如上文定義之一或多個芳基。芳烯基之芳基 128409 -31 - 200836743 部份可視情況如上文關於芳基所述經取代。芳烯基之次歸 基鏈部份可視情況如上文關於次烯基所定義經取代。 芳炔基”係指式-R^Rc基團，其中為如上文定義之次炔 基鏈，且Re為如上文定義之一或多個芳基。芳炔基之芳基 邛知了視丨月况如上文關於芳基所述經取代。芳炔基之次块 基鏈部份可視情況如上文關於次炔基鏈所定義經取代。 ，％烷基’’係指安定非芳族單環狀或多環狀烴基，僅由碳 與氫原子組成，其可包含經稠合或橋接之環系統，具有^ 至十五個碳原子，較佳係具有三至十個碳原子，且其係為 飽和或不飽和，並藉由單鍵連接至分子之其餘部份。單環 狀基團包括例如環丙基、環丁基、環戊基、環己基、環庚 及％辛基。多環狀基團包括例如金鋼烷基、正蓓基、十氕 萘基、7,7-二甲基-雙環并[2.Z1^烷基等。除非在本專利說 明書中另有明確述及，否則”環烷基” 一詞係意謂包括環烷 基，其係視情況被一或多個取代基取代，取代基獨立選自 包括烷基、烯基、_基、_烷基、_烯基、氰基、硝基、 酮基、芳基、芳烧基、環烧基、環烧基烧基、雜環基、雜 環基烧基、雜芳基、雜芳烷基、_r15-〇rM、H〇c(〇)_Rl4、 -R15-N(R14)2 > -R15-C(0)R14 . -Rl 5.C(0)0Rl 4 Λ .Ri5.C(〇)N(Rl4)2 . -R15-N(R14)C(0)0R^ . , -Ri5.N(Ri4)S(〇)tRl6 (其中 t 為 1 至 2)、-R15-N=c(〇r14)r14、及15_s(〇)t〇Rl6(其中 t 為 1 至 2)、-R1 5 -s(0)p Ri 6 (其中 p 為 〇 至幻及 _Rl 5 _s(〇^n(r1 4 M 其 中t為1至2)，其中各R14係獨立為氫、烷基、由烷基、環烷 基、環烷基烷基、芳基、芳烷基、雜環基、雜環基烷基、 128409 -32- 200836743 雜务基或雜芳燒基，·各丨5 ^ ^A ^ ^ ^ 、蜀為直接鍵結或直鏈或分枝 狀-人坑基或-人稀基鏈；且各Rl6為燒 環烷基烷基、芳基-基衣烷基、 基或雜芳烧基。 土、雜壤基、雜環基院基、雜芳 裱烷基烷基’，係指式-RbRg* u s公叫六τ %苟如上文定義之 次烧基鏈，且R為如 疋義之 文疋義之$ 衣烷基。次烷基鏈與環烷 基可視情況如上文定義經取代。 ”環烷基烯基” 4 D 〇ί 酉 The same base refers to the =0 substituent. The thioketo group π means a =s substituent. "Trifluoromethyl" means a -CF3 group. "Alkyl" means a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms 'not containing + saturation, having one to twelve carbon atoms 'It is preferably one to eight carbon atoms or - to six carbon atoms, and is linked to the rest of the molecule by a single bond, such as methyl, ethyl, n-propyl, methyl ethyl (rivide), n-butyl, n-pentyl, U-dimethylethyl (t-butyl), 3-methylhexyl, 2-methylhexyl, etc., unless otherwise stated in this patent specification Said that 'other bases may be substituted by one of the following groups: leukoyl, alkenyl, functional, alkenyl, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, Keto group, trimethyl base, preparation ", qing)_r1 4, _n(ri 4 )2, -C(〇)R-^-C(〇)〇Rl4 , .C(0)N(r14) 2 ^ _N(r14)c(〇)〇r16 ^ -N(R-)C(0)R16 , -N(RI4)S(〇)tRl6(^ t 2 _s(〇)t〇Rl6(^ 中t Is 1 to 2), _S(〇)pRl6 (where P is 〇 to 2) and -S_(R")2 (where t = to 2), wherein each R" is independently chlorine, 炫, 幽, cycloalkyl, % alkane An alkyl group, an aryl group, an arylalkyl group, a heterocyclic group, a heterocyclic alkyl group, a heteroaryl group 128409 -26 - 200836743 or a heteroarylalkyl group; and each R16 is an alkyl group, an alkyl group, a cycloalkyl group, Cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl. Alkenyl '' refers to a straight or branched hydrocarbon chain radical, only Consisting of carbon and hydrogen atoms, containing at least one double bond, having from two to twelve carbon atoms, preferably from one to eight carbon atoms, and which is attached to the remainder of the molecule by a single bond, r such as a vinyl group , propyl + alkenyl, butenyl, pentane, pentyl, pentyl, pentyl, pentyl, pentyl, pentylene, etc.. Unless otherwise specifically stated in this specification, an alkenyl group may be substituted by one of the following groups: Base, alkenyl, yl, alkenyl, cyano, nitro, aryl 'cycloalkyl, heterocyclyl, heteroaryl, keto, tri-, -C(〇)Rl methyl decyl, OR1 C(0)0R, _C(0)N(R14)2, -N(R14)C(0)0R16, _n(R14)C(〇)R16, -N(R"just tRl6(where t is i To 2), _s(〇)t〇Rl6 (where t is i to 2), S(〇)pRl 6 (where P is 0 to 2) and -. Difficult 14) 2 (wherein t is 1 to 2), wherein each R 14 is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, hetero a cycloalkyl, heteroaryl or heteroarylalkyl group; each R is an alkyl group, a halogen group, a cycloalkyl group, a cycloalkyl group, an aryl group, an aryl group, a heterocyclic group, a heterocyclic group , heteroaryl or heteroaryl. "alkynyl" refers to a straight or branched tobacco chain group consisting of only carbon and a hydrogen atom 'containing at least one reference bond, optionally containing at least one double bond, having: to twelve carbon atoms Preferably, it is two to one carbon atom, and is linked to the rest of the molecule by an early bond, such as an ethyl group, a (tetra) group, a crust, a fluorene group, a hexyl group, etc., unless the patent It is also explicitly stated in the specification, otherwise the block group may be substituted by - or more than one of the following substituents: alkyl, 128409 -27-200836743, divalent, (tetra), i-alkenyl, cyano, schiffyl, aryl, (tetra) , heterocyclic group, heteroaryl group, keto group, trimethyl group, 〇R14, 〇c(〇)-r14, -N(R-)2 . .C(〇)〇Ru . .C(〇 N(r14)2 ^ _N(r14)c(〇)〇r16 ^ -N(R-)C(0)R-. -N(R-)S(0)tRU(^ t t4 t £2) ^ _s(〇)t〇Rl6(^ where t is 1 to 2), -S(0)PR 6 (where p is 〇 to 2), and _s(〇)tN(Rl 4 )2 (where t is 1 To 2), wherein each Rl4 is independently hydrogen, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or hetero Fang burned for Alkyl, aryl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl. A base chain '' refers to a linear or branched bivalent hydrocarbon chain that links the remainder of the molecule to a group, consists solely of carbon and hydrogen, does not contain unsaturation, and has from one to twelve carbon atoms, such as Amidinoyl, ethethylene, propylene, n- butyl, etc. The alkylene chain is attached to the remainder of the molecule via a single bond' and passes through a single bond to the group. The remainder of the injury and the point of attachment to the group may pass through one carbon or any two carbons in the chain. Unless otherwise specifically stated in this patent specification, the secondary alkyl chain may be replaced by one of the following groups: An alkyl group, an alkenyl group, a halogen group, an alkenyl group, a cyano group, a decyl group, a aryl group, a benzyl group, a heteroaryl group, a heteroaryl group, a benzyl group, a trimethyl decyl group, -OR14, -OCXOH14, -NCR14 )2, -C(0)R14, -C(〇)〇Ri 4, ^(Ο)Ν(Κ14 )2 ^ -NCR1 4 )C(0)0R1 6 ^ -NCR1 4 )C(0) R1 6 > ^(R1 4 )S(0)t ^ (where t is 1 to 2), -S(0) t0R16 (where t is 1 to 2), -S(0)pRi6 (where p is 〇 to 2) and -S(0)tN(R14)2 (where t is 1 to 2), wherein each Ri4 is independent Gas, alkyl, ketone, cycloalkyl, cycloalkyl, aryl, aryl, 128409 -28 - 200836743 heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; And each R10 is an alkyl group, a halogen-based group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group, a heterocyclic group, a heterocyclic group, a heteroaryl group or a heteroaryl group. "Subalkenyl" and "alkenyl chain" means a straight or branched divalent hydrocarbon chain linking the remainder of the molecule to a group consisting solely of carbon and hydrogen, containing at least one double bond, and having Two to twelve carbon atoms, such as a vinylidene group, a propylene group, a n-butenyl group, and the like. The secondary alkenyl chain is attached to the remainder of the molecule via a single bond and to the group via a double bond or a single bond. The secondary alkenyl chain may pass through one or both of the carbons in the remainder of the molecule and the point of attachment to the group. Unless otherwise specifically stated in this patent specification, the secondary alkenyl chain may be optionally substituted by one of the following groups: alkyl, alkenyl, yl, haloalkenyl, cyano, nitro, aryl, cyclo Alkyl, heterocyclic, heteroaryl, keto, trimethyldecyl, 〇 〇 Rl 4, _〇c(9)·Rl 4, _n(r1 4 )2, _c(〇)r1 4, -C(0 ) 0R14 . -C(0)N(R14)2 . -N(R14)C(0)0R16 ^ ^(R14 )0(〇)^6 ^ •N(R14)S(〇)tRi6 (where t is i to 2), _s(〇)t〇Rl6 (where t is [to, -S(〇)pR16 (where p is 〇 to 2) and _s(〇XN(Rl4)2 (where t is i to 2) Wherein each R is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroaryl Alkyl; and each R is alkyl, !I[alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroaralkyl ''-alkynyl' or 'para-alkynyl-chain' means a straight-chain or branched divalent hydrocarbon chain, the remainder of the knives, and the knives, consisting solely of carbon and hydrogen, Contains at least one key and has There are two to twelve carbon atoms, such as the subpropynyl group, the n-alkynyl group. The nalynyl chain is attached to the rest of the molecule via a single bond. 128409 -29- 200836743 and, two over double bonds or Single bond to the group. The attachment point of the nalynyl chain to the remaining IM knives and the group of the molecule may be reversed by one carbon or any two stones in the chain unless otherwise specifically stated in this patent specification. , otherwise the alkynyl chain may be optionally substituted by the following groups: a pyridyl group, a dilute group 4 group, a (tetra) group, a murine group, a nitro group, an aryl group, a cycloalkyl group, a heterocyclic group, a heteroaryl group, a ketone. , trimethyldecyl, -〇Rl4, ·〇(::(〇>]^14, -N(Rl4)2, _c(〇)rM, -C(0)〇R^ . -C( 0)N(R14)2 . -N(R14)C(0)0R16 . -N(R^)C(0)R16 . -N(Rl4)S(〇)tRl6 (where t is 1 to 2), -S(0)t〇Ri6 (where t is i to 2), •S(〇)pR16 (where p is 0 to 2), and _8(〇)_14)2 (where ... to illusion, where each H1) a hydrogen, a pyridyl group, a dentate group, a cycloalkyl group, a cycloalkyl group, an aryl group, an arylalkyl group, a heterocyclic group, a heterocyclylalkyl group, a heteroaryl group or a heteroarylalkyl group; and each R16 For alkyl, halogen & amp a group, a cycloalkyl group, a decylalkyl group, an aryl group, an arylalkyl group, a heterocyclic group, a heterocyclic group, a heteroaryl group or a heteroaryl group. A group, wherein Ra is an alkyl group as defined above, containing from one to twelve carbon atoms. The alkyl portion of the alkoxy group may be optionally substituted as defined above for the alkyl group. ''Alkoxyalkyl" refers to a radical of the formula _Rb-〇-Ra wherein is converted to an alkylene chain as defined above, and Ra is an alkyl group as defined above. The oxygen atom may be bonded to the secondary alkyl chain Any carbon with a burnt base. The portion of the burnt (four) base may be substituted as defined above for the burn group. The secondary bond of the 6 oxon may be replaced as defined above for the secondary alkyl chain. An aryl-based hydrocarbon system group comprising hydrogen, 6 to 18 carbon atoms, and at least one aromatic ring. For the purposes of the present invention, the aryl group may be monocyclic, bicyclic, tricyclic or A four-ring ring system, which may include a ring system that is fused or bridged 128409 -30 - 200836743. The aryl group includes, but is not limited to, derived from terpene, terpene, terpene, fluorene, quinone, benzene, fluorene , 苐, as_茚莘, s_茚莘, hydroquinone, hydrazine, hydrazine, sulfonium, phenanthrene, phenoxy, valerene and phenylphenanthrene. Unless otherwise stated in this patent specification, " The word "aryl" or "head" "芳_" (for example, in "aryl") means that the aryl group is optionally replaced by - or multiple Substituted 'substituents are independently selected from the group consisting of alkyl, alkenyl, —yl,^alkylhaloenyl, cyano, nitro, aryl, heteroaryl, heteroarylalkyl, _R" _〇Rl 4, - R15_0C(0)-R", -R15_N(Rl4)2, _r15_c(〇)r14, _r15 _c(〇)〇r14 -R15-C(0)N(R14)2, -R15-N(R14)C( 0) 0R16, -r15_n(ri4)c(〇)r16, -R15-N(R14)S(0)tR16 (where t is 1 to 2)...Rl5_N=c(ORl4)Rl4, -Ri 5-S( 0)t OR "(where t is i to 2), -Rl 5 ·8(〇)ρ R1 6 (where p is 〇 to illusion and -R15-S(0)tN(R14)2 (where t is 1 To 2), wherein each Rm is independently hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkyl, aryl, aryl, heterocyclyl, heterocyclylalkyl, heteroaryl or a heteroaralkyl group; each of the R 5 groups is independently a direct bond or a straight bond or a branched sub- or a sulfhydryl bond; and each R 6 is a group, iS alkyl, cycloalkyl or cycloalkylane. a aryl group, an aryl group, a heterocyclic group, a heterocyclylalkyl group, a heteroaryl group or a heteroaralkyl group. The π arylalkyl group '' refers to a group of the formula -Rb -Rc, wherein Rb is as defined above a secondary base chain, and Re is one or more of the above defined For example, a benzyl group or a bis-methyl group may be substituted as described above for the alkylene chain. The aryl portion of the aralkyl group may be as described above for the aryl group. "Aralkenyl" refers to a radical of the formula -RcrRc, wherein Rd is a minor dilute chain as defined above, and Rc is one or more aryl as defined above. Aryl groups of aralkenyl groups 128409 - 31 - 200836743 Some of the cases may be substituted as described above for aryl groups. The sub-base chain portion of the aralkenyl group may be optionally substituted as defined above for the hypoalkenyl group. "Aralkynyl" refers to a radical of the formula -R^Rc, wherein is a nalienyl chain as defined above, and Re is one or more aryl groups as defined above. The aryl group of the aralkynyl group is known The monthly conditions are as described above for the aryl group. The sub-blocky chain portion of the aralkynyl group may be substituted as defined above for the nalynyl chain. The % alkyl '' refers to the stable non-aromatic monocyclic ring. a polycyclic or polycyclic hydrocarbon group consisting solely of carbon and hydrogen atoms, which may comprise a fused or bridged ring system having from 15 to 15 carbon atoms, preferably from three to ten carbon atoms, and It is saturated or unsaturated and is attached to the rest of the molecule by a single bond. Monocyclic groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and %octyl. The group includes, for example, a gold steel alkyl group, a n-decyl group, a decathenyl group, a 7,7-dimethyl-bicyclo[2.Z1^alkyl group, and the like. Unless otherwise specifically stated in the specification, Otherwise the term "cycloalkyl" is intended to include cycloalkyl, which is optionally substituted by one or more substituents independently selected from alkyl, alkenyl. , _ group, _alkyl, alkenyl, cyano, nitro, keto, aryl, aryl, cycloalkyl, cycloalkyl, heterocyclyl, heterocyclyl, heteroaryl Base, heteroaralkyl, _r15-〇rM, H〇c(〇)_Rl4, -R15-N(R14)2 > -R15-C(0)R14 . -Rl 5.C(0)0Rl 4 Λ .Ri5.C(〇)N(Rl4)2 . -R15-N(R14)C(0)0R^ . , -Ri5.N(Ri4)S(〇)tRl6 (where t is 1 to 2), - R15-N=c(〇r14)r14, and 15_s(〇)t〇Rl6 (where t is 1 to 2), -R1 5 -s(0)p Ri 6 (where p is 〇 to illusion and _Rl 5 _s(〇^n(r1 4 M wherein t is 1 to 2), wherein each R14 is independently hydrogen, alkyl, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, hetero Cyclo, heterocyclylalkyl, 128409 -32- 200836743 hydroxy or heteroaryl, · 5 ^ ^ A ^ ^ ^, 蜀 is a direct bond or a linear or branched - pit Or a human dilute base chain; and each R16 is a cycloalkylalkylalkyl group, an aryl-alkyl group, a aryl group or a heteroarylalkyl group. A soil, a heterobasic group, a heterocyclic group, a heteroarylalkyl group Alkyl', refers to the formula -RbRg*us, publicly called six τ %, such as the sub-alkyl chain defined above, and R is as Cloth sense of the text of $ alkyl clothes. Alkylidene chain cycloalkyl group optionally substituted as defined above. "Cycloalkylalkenyl" 4 D square

埽土係扣式-RdRg基團，其中^為如上文定義之 认稀基鍵’且R為如卜寺企 上文疋義之裱烷基。次烯基鏈與環烷 基可視情況如上文定義經取代。 "環烷基炔基”係指式·W基團，其中匕為如上文定義之 次块基，且Rg為如上文定義之環烧基。次块基鏈與環烧基 可視炀況如上文定義經取代。 ”經稠合’’係指本文中所述之任何環系統，其係稠合至本 1月化。物中之現存環結構。當稠合環系統為雜環基或雜 芳基時，會變成稠合環系統之一部份之現存環結構上之任 何碳原子可被氮原子置換。 Π鹵基”係指溴基、氣基、氟基或碘基。 Η鹵烷基”係指如上文定義之烷基，其係被-或多個如上 文定義之鹵基取代，例如三氟甲基、二氟甲基、三氯甲基、 2,2,2-三氟乙基、；μ氟基甲基·2_氟基乙基、3_溴基么氟基丙基、 1-漠基甲基冬溴基乙基等。_烷基之烷基部份可視情況如上 文關於烷基所定義經取代。 鹵烯基”係指如上文定義之烯基，其係被一或多個如上 128409 -33 - 200836743 烷基之烯基部份可視情況如上文關 文定義之_基取代。鹵 於烯基所定義經取代。 炔基”係指如上文定義之炔基，其係被一或多個如上 文定義之i基取代。i烷基之炔基部份可視情況如 上文關 於炔基所定義經取代。 ’’雜環基”係指安定3-至18-員非芳族環基團，其包含二至 十二個碳原子與一至六個選自包括氮、氧及硫之雜原子。The bauxite-bonded-RdRg group, wherein ^ is a dilute base bond as defined above and R is a decyl group as defined above. The alkenyl chain and the cycloalkyl group may be substituted as defined above. "cycloalkylalkynyl" refers to a group of formula W wherein 匕 is a subblock as defined above and Rg is a cycloalkyl group as defined above. The secondary block chain and the cyclized group may be as above The definitions are substituted. "Fused" refers to any of the ring systems described herein that are fused to this January. The existing ring structure in the object. When the fused ring system is a heterocyclic or heteroaryl group, any carbon atom on the existing ring structure which becomes part of the fused ring system can be replaced by a nitrogen atom. "Π halo" means bromo, va, fluoro or iodo. "haloalkyl" means an alkyl group as defined above substituted by - or a plurality of halo groups as defined above, eg, trifluoro Methyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, μfluoromethyl-2-fluoroethyl, 3-bromofluoropropyl, 1- Moji methyl winter bromoethyl and the like. The alkyl portion of the alkyl group may be substituted as defined above for the alkyl group. "Haloalkenyl" means an alkenyl group as defined above which is substituted by one or more of the alkenyl moieties of the above-mentioned 128409-33 - 200836743 alkyl group as defined above. Definitions Substituted. "Alkynyl" means an alkynyl group as defined above substituted by one or more i groups as defined above. The alkynyl moiety of the i-alkyl group may optionally be substituted as defined above for the alkynyl group. ''Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic cyclic group comprising from two to twelve carbon atoms and one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur.

除非本專利說明書中另有明確述及，否則雜環基可為單學 狀、雙環狀、三環狀或四環狀環系統，其可包含經祠合或 橋接之環系統，·且在雜環基中之氮、碳或硫原子可視情況Unless specifically stated otherwise in the specification, a heterocyclic group can be a single-study, bicyclic, tricyclic or tetracyclic ring system, which can include a twisted or bridged ring system, and The nitrogen, carbon or sulfur atom in the heterocyclic group may be as the case may be

書中另有明確述及，否則”雜環基，，一 被氧化；氮原子可視情況被四級化；及雜環基可為部份或 完全飽和。此種雜環基之實例包括但不限於二氧伍圜基、 魂吩基[1，3]二硫陸圜基、十氫異喹啉基、二氫咪唑基、四气 咪唑基、異噻唑啶基、異四氫噚唑基、嗎福啉基、八氫; 哚基、八氫異啕哚基、基六氫吡畊基、2,基六氫吡啶 基、2-酮基四氫吡咯基、四氫，号唑基、六氫吡啶基、六氕 吡畊基、4-六氫吡啶酮基、四氫吡咯基、四氫吡咯_基、 四氫吡唑基”昆啶基、嘍唑啶基、四氫呋喃基、三硫陸圜 基、四氫喊喃基、硫代嗎福#基、硫基嗎福#基、r嗣基_ 硫代嗎福#基及1，1·二酮基·硫代嗎射I。除非本專利說明 d係意謂包括如上文 定義之雜環基’其係視情況被—或多個取代基取代，取代 基選自包括院基、烯基、鹵基、鹵院基、處稀基、氛基、 酮基、硫酮基、石肖基、若某菩P其 方丞方烷基裱烷基、環烷基烷 128409 -34- 200836743 基、雜環基、雜環基烷基、雜芳基、雜芳烷基、_r1s_〇r14、 -R15-0C(0>R14 . .R15.N(R14)2 , .R15„C(〇)R14 , -R15.C(〇)〇r14 ^ -R15-C(0)N(R14)2、_R15_N(R14)C(0)0R16、_r15 -N(r14)c(〇)r16、 -R15-N(R14)S(〇)tRi6(其中 t 為 i 至 2)、_r15_n==c(〇r14)r14、 -R15 -S(0)t ORi 6 (其中 t 為】至 2)、ns(〇)p Rl 6 (其中 p 為 〇 至 2) 及-R15-S(0)tN(RH)2(其中1為1至2)，其中各rh係獨立為氫、 烷基、烯基、i烷基、環烷基、環烷基烷基、芳基、芳烷 基、雜環基、雜環基烷基、雜芳基或雜芳烷基；各…5係獨 立為直接鍵結或直鏈或分枝狀次烷基或次烯基鏈；且各ru 為烷基、烯基、_烷基、環烷基、環烷基烷基、芳基、芳 烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基。 ’’N-雜環基”係指如上文定義之雜環基，含有至少一個氮， 且其中雜環基對分子其餘部份之連接點係經過雜環基中之 虱原子。N-雜環基可視情況如上文關於雜環基所述經取代。 雜環基烷基”係指式-RbRh基團，其中^為如上文定義之 -人烷基鏈，且Rh為如上文定義之雜環基，而若雜環基為含 氮雜環基’則雜環基可連接至烧基，在該氮原子上。雜環 基烧基之次烧基鏈可視情況如上文關於线基鏈所定義經 取代。雜娘基烷基之雜環基部份可視情況如上文關於雜環 基所定義經取代。 、 /雜環基焊基"係指式-响基團，其中〜為如上文定義之 人稀基鏈’且Rh為如上文定義之雜環基，而若雜環基為 氮雜環基，㈣環基可連接至次縣鏈，在錢原子上。 ㈣基稀基之次烯基鏈可視情況如上文關於次稀基鍵所定 128409 -35· 200836743 義經取代。雜環暮檢I — & ^ 土之雜環基部份可視情況如上文關於 雜環基所定義經取代。 雜壞基快基’’伟批斗、η ^ ’、曰式-ReRh基團，其中心為如上文定義之 次炔基鏈，且&兔‘ u 4 ~ ^ 长 、 疋義之雜環基，而若雜環基為含 風雜％基’則雜環基可連接至炔基，在該氮原子上。雜環 土丈、基之人块基鏈部份可視情況如上文關於次炔基鏈所定 義縣代。雜環基块基之雜環基部份可視情況如上文關於 雜環基所定義經取代。 ”雜芳基"係指5_至沐員環系統基團，包含氫原子，一至 十三個碳原子，一至六個選自包括氮、氧及硫之雜原子， ^至少一個芳族環。對本發明之目的而言，雜芳基可為單 狀、雙環狀或：r提也；^ 四/ /一衣狀哀系統，其可包含經稠合或橋接之 環系統；而在雜笑其φ ^ ^ · 基中之任何氮、碳或硫原子可視情況被 氧化，且任何氮原子可視情況被四級化。對本發明之目的 而口雜方基之芳族環未必含有雜原子，只要雜芳基之一 個環含有雜原子即可。實例包括但不限於一氮七圜烯基、 「疋基苯并咪唑基、苯并嘍唑基、苯并吲哚基、苯并二 氧伍圜烯基、苯并吱喃基、苯并号唾基、苯并違。坐基、苯 ^塞二唾基、苯并剛4]二氧氮七圜烯基、㈣并二氧陸 :基、苯并萘并呋喃基、苯并噚唑基、苯并二氧伍圜烯基' 苯并二^陸圜稀基、苯并喊喃基、苯并喊喃酮基、苯并吱 喃基、苯并呋喃酮基、苯并噻吩基（苯并硫苯基）、苯并三 坐基、本开[4’6]咪唾并[1»比咬基、苯并十坐琳酉同基、咔 坐基Ή基、二苯并吱〶基、二苯并苯硫基、吱喃基、 128409 -36· 200836743 吱喃酮基、異p塞唾基、味。坐基、4峻基、^丨嗓基、Η丨峻基、 異吲哚基、二氫啕哚基、異4哚啉基、異喹啉基、啕畊基、 異崎唑基、喑啶基、啰二唑基、2-氧一氮七圜烯基、噚唑 基、環氧乙烧基、1-氧化p比唆基、1-氧化嗜唆基、1-氧化π比 畊基、1-氧化嗒畊基、1-苯基-1H-吡咯基、啡畊基、啡噻畊 基、啡嘮畊基、呔畊基、喋啶基、喋啶酮基、嘌呤基、吡 哈基、p比σ坐基、TT比σ定基、P比17定g同基、p比P井基、喷σ定基、。密 °疋綱基、σ合哨基、卩比洛基、卩比σ定弁[2,3-d]^唆銅基、τι奎σ坐ρ林 基、Ρ奎唾淋酮基、ρ奎嘆琳基、0奎嗟琳_基、峻淋基、異峻 琳基、四氫4琳基、碟唑基、嘧二唑基、嘧吩并[3,2-d]嘧啶 -4-酮基、P塞吩并[2,3-d]嘧啶-4-酮基、2-硫酮基苯并咪唑基、 三唑基、四唑基、三畊基及硫苯基（意即嘍吩基）。除非本 專利說明書中另有明確述及，否則，，雜芳基” 一詞係意謂包 括如上文定義之雜芳基，其係視情況被一或多個取代基取 代’取代基選自包括烷基、烯基、烷氧基、_基、_烷基、 鹵烯基、氰基、酮基、硫酮基、硝基、硫酮基、芳基、芳 烷基、環烷基、環烷基烷基、雜環基、雜環基烷基、雜芳 基、雜芳烷基、HORM、-Rl5_〇c(〇>Rl4、_Rl5啊Rl4)2、 -R15-C(0)R14 、 -R15-C(0)0R14 、 _] 、-R15-C(0)N(R14)2It is also explicitly stated in the book that otherwise, "heterocyclyl, one is oxidized; the nitrogen atom may be quaternized as appropriate; and the heterocyclic group may be partially or fully saturated. Examples of such heterocyclic groups include but not Restricted to dioxinyl, phenanthyl [1,3] dithiorepine, decahydroisoquinolinyl, dihydroimidazolyl, tetram imidazolyl, isothiazolidinyl, isotetrahydrocarbazolyl, , morpholinyl, octahydro; fluorenyl, octahydroisodecyl, hexahydropyridinyl, 2,ylhexahydropyridyl, 2-ketotetrahydropyrrolyl, tetrahydro, oxazolyl, hexa Hydropyridyl, hexahydropyridyl, 4-hexahydropyridinyl, tetrahydropyrrolyl, tetrahydropyrrole-yl, tetrahydropyrazolyl quinacridyl, oxazolidinyl, tetrahydrofuranyl, trisulfide Sulfhydryl, tetrahydropyranyl, thiofolf #基, thiophene# base, r嗣 group _ thio carbazyl and 1,1,dionethiol. Unless the present specification d is intended to include a heterocyclyl group as defined above, which is optionally substituted with a plurality of substituents, the substituents are selected from the group consisting of a group, an alkenyl group, a halo group, a halogen group, and a dilute group. Base, aryl group, keto group, thioketo group, schiffyl group, ruthenium phenyl hexanyl decyl group, cycloalkyl alkane 128409 -34- 200836743 base, heterocyclic group, heterocyclic alkyl group, hetero Aryl, heteroaralkyl, _r1s_〇r14, -R15-0C(0>R14 . .R15.N(R14)2 , .R15„C(〇)R14 , -R15.C(〇)〇r14 ^ -R15-C(0)N(R14)2, _R15_N(R14)C(0)0R16, _r15 -N(r14)c(〇)r16, -R15-N(R14)S(〇)tRi6(where t i to 2), _r15_n==c(〇r14)r14, -R15 -S(0)t ORi 6 (where t is ] to 2), ns(〇)p Rl 6 (where p is 〇 to 2) And -R15-S(0)tN(RH)2 (wherein 1 is 1 to 2), wherein each rh is independently hydrogen, alkyl, alkenyl, ialkyl, cycloalkyl, cycloalkylalkyl, Aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each 5 is independently a direct bond or a linear or branched alkyl or subalkenyl chain And each ru is an alkyl group, an alkenyl group, or an alkane , cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl. ''N-heterocyclyl" means as defined above a heterocyclic group containing at least one nitrogen, and wherein the point of attachment of the heterocyclic group to the rest of the molecule is through a hetero atom in the heterocyclic group. The N-heterocyclic group may be optionally substituted as described above for the heterocyclic group. "Heterocyclylalkyl" refers to a radical of the formula -RbRh wherein ^ is a human alkyl chain as defined above, and Rh is a heterocyclyl group as defined above, and if the heterocyclyl is a nitrogen-containing heterocyclic radical 'The heterocyclic group may be attached to the alkyl group on the nitrogen atom. The secondary alkyl group of the heterocyclic group may be substituted as defined above for the linear chain. The heterocyclic base of the heteroaryl group The moiety may be substituted as defined above for a heterocyclic group. / /heterocyclyl base "," refers to a radical, wherein - is a human dilute chain as defined above and Rh is as defined above a heterocyclic group, and if the heterocyclic group is a nitrogen heterocyclic group, the (iv) ring group may be attached to the sub-counter chain at the money atom. (4) The sub-alkenyl chain of the base group As described above for the sub-dense bond, 128409-35·200836743 is substituted. The heterocyclic ring test I — & ^ The heterocyclic moiety of the soil can be substituted as defined above for the heterocyclic group. a group of ''Wei's, η^', 曰-ReRh groups, the center of which is a subalkynyl group as defined above, and & rabbit 'u 4 ~ ^ long, heterocyclic heterocyclic group, and The base is a heteroatom group, and the heterocyclic group may be attached to an alkynyl group on the nitrogen atom. The heterocyclic ring and the base block of the human base can be as defined above for the subalkyny chain. The heterocyclic moiety of the heterocyclic block group may be optionally substituted as defined above for the heterocyclic group. "Heteroaryl" means a group of 5 to a member of the ring system comprising a hydrogen atom, one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, ^ at least one aromatic ring For the purposes of the present invention, a heteroaryl group may be mono-, bicyclic or: r-r-; ^ a// a smear system, which may comprise a fused or bridged ring system; Any nitrogen, carbon or sulfur atom in the φ ^ ^ · group may be oxidized as appropriate, and any nitrogen atom may be quaternized as appropriate. For the purposes of the present invention, the aromatic ring of the heterocyclic group does not necessarily contain a hetero atom, As long as one ring of the heteroaryl group contains a hetero atom, examples include, but are not limited to, a heptaerythrenyl group, a "mercaptobenzimidazolyl group, a benzoxazolyl group, a benzofluorenyl group, a benzodioxan group. Terpene, benzopyranyl, benzo-s-yl, benzo-inhibited. Sodium, benzo-di-saltyl, benzo- 4]dioxa-7-alkenyl, (iv) dioxane: Benzonaphthylfuranyl, benzoxazolyl, benzodioxolanyl' benzoxanthene, benzoxanyl, benzopyranyl, benzo吱 基, benzofuranone, benzothienyl (benzothiophenyl), benzotrisyl, phenyl [4'6] imi-[1» than bite, benzo-ten酉同基,咔基基基, dibenzofluorenyl, dibenzophenylthio, fluorenyl, 128409 -36· 200836743 anthranone, iso-p-salt, taste. Junki, fluorenyl, fluorenyl, isodecyl, indanyl, iso- 4 porphyrin, isoquinolinyl, hydrazine, isnzazolyl, acridinyl, anthracene Azolyl, 2-oxo-nitrosopentenyl, carbazolyl, oxirane, 1-oxidized p-indenyl, 1-oxidized oxime, 1-oxidized pi-ratio, 1-anthracene Tillage, 1-phenyl-1H-pyrrolyl, phenylidene, thiophene, cultivating, cultivating, acridinyl, acridinone, sulfhydryl, pyrhadyl, p-ratio Sitting base, TT ratio σ base, P ratio 17 fixed g same base, p ratio P well base, jet σ fixed base, dense 疋 疋 base, σ combined whistle base, 卩 洛 洛 洛, 卩 σ σ 弁 弁 [2 ,3-d]^唆 copper base, τι奎σ sitting ρ 林基, Ρ奎唾 酮 ketone base, ρ奎叹琳基, 0奎嗟琳_基, 峻淋基, 异峻琳基,四4 Lin-based, oxazolyl, pyrimidazolyl, pyrimido[3,2-d]pyrimidin-4-one, P-seceno[2,3-d]pyrimidin-4-one, 2- a thioketobenzimidazolyl group, a triazolyl group, a tetrazolyl group, a tritonyl group, and a thiophenyl group (ie, a porphinyl group). Unless otherwise specifically stated in the specification, a heteroaryl group The word system is intended to include a heteroaryl group as defined above, which is optionally substituted with one or more substituents. The substituent is selected from the group consisting of alkyl, alkenyl, alkoxy, yl, _alkyl, haloalkyl. Base, cyano, keto, thioketo, nitro, thioketo, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, Heteroaralkyl, HORM, -Rl5_〇c (〇>Rl4, _Rl5, Rl4)2, -R15-C(0)R14, -R15-C(0)0R14, _], -R15-C( 0)N(R14)2

環烷基、環烷基烷基、芳基、 W 至 2)及-R” -SCOXNCR1 4 )2 (其 為氫、烷基、烯基、_烷基、 芳烷基、雜環基、雜環基烷 128409 -37- 200836743 7基、雜芳基或雜芳烧基；各Rl5係獨立為直接鍵結或直鍵或 分枝狀次㈣或次縣鏈；且各Rl6為烧基、烯基、鹵烧基、 環烧基、環烷基烷基、芳基、 不丞方烷基、雜裱基、雜環基烷 基、雜芳基或雜芳烷基。 ”队雜芳基”係指如上文定義之雜芳基，含有至少一個氮， 且其中雜芳基對分子其餘部份之連接點係經過雜芳基中之 氮原子。N-雜芳基可視情況如上文關於雜芳基所述經取代。Cycloalkyl, cycloalkylalkyl, aryl, W to 2) and -R" -SCOXNCR1 4 )2 (which are hydrogen, alkyl, alkenyl, _alkyl, aralkyl, heterocyclyl, hetero Cycloalkane 128409 -37- 200836743 7-based, heteroaryl or heteroaryl; each Rl5 is independently a direct bond or a straight bond or a branched sub- (four) or sub-counter chain; and each R16 is a burnt or alkene a group, a haloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, a non-nonyl, a heteroalkyl group, a heterocyclylalkyl group, a heteroaryl group or a heteroarylalkyl group. Means a heteroaryl group as defined above, containing at least one nitrogen, and wherein the point of attachment of the heteroaryl group to the remainder of the molecule is through a nitrogen atom in the heteroaryl group. The N-heteroaryl group can be as described above for heteroaryl The base is substituted.

雜方烷基”係指式_RbRi基團，其中Rb為如上文定義之次 烷基鏈’且Ri為如上文定義之雜芳基。雜芳烷基之雜芳基 部份可視情況如上文關於雜芳基所定義經取代。雜芳烧基 之次院基鏈部料視情況如上文關於次烧基鏈所定義經取 代0 ’’雜芳基烯基”係指式_RdRi基團，其中^為如上文定義之 次烯基鏈，且&為如上文定義之雜芳基。雜芳基稀基之雜 芳基部份可視情況如上文關於雜芳基所定義經取代。雜芳 基稀基之次烯&鏈部份可視情況如上文關於次稀基鍵所定 義經取代。 ”雜芳基炔基，，係指式-ReRi基團，其中Re為如上文定義之 次炔基鍵，且Ri為如丨文定義之雜芳基。雜芳基快基之雜 芳基部份可視情況如上文關於雜芳基所定義經取代。雜芳 基炔基之次炔基鏈部份可視情況如上文關於次炔基鏈所定 義經取代。 罗工烷基係扎如上文定義之烷基，被一或多個羥基取代。 ’’止痛法’’係指於正常情況下回應刺激會痛苦之疼痛不存 128409 •38- 200836743 在。 "感覺異常"係指其中於正常情況下無害之知 見 言如壓 力或輕微接觸，被感覺為極端地痛苦之症狀。 :’前體藥物"係意欲表示可在生理學條件下或藉由溶劑分 解被轉化成本發明生物活性化合物之化合物。 ”二 u 达匕， Hif"Hetero-alkyl" refers to a radical of the formula _RbRi wherein Rb is a secondary alkyl chain as defined above and Ri is a heteroaryl group as defined above. The heteroaryl portion of a heteroarylalkyl group may be as above With respect to the substituents defined by the heteroaryl group, the sub-base chain moiety of the heteroaryl group is optionally substituted with a 0 ''heteroarylalkenyl group' as defined above for the sub-alkyl group, _RdRi group, Wherein ^ is a secondary alkenyl chain as defined above, and & is a heteroaryl group as defined above. The heteroaryl portion of the heteroaryl dilute group can be optionally substituted as defined above for the heteroaryl group. The olefinic & chain moiety of the heteroaryl azo group can be optionally substituted as defined above for the sub-dense bond. "Heteroarylalkynyl", which refers to a radical of the formula -ReRi, wherein Re is a hypoalkynyl bond as defined above, and Ri is a heteroaryl group as defined in the above. Heteroaryl radicals of a heteroaryl radical The moiety may be substituted as defined above for the heteroaryl group. The hypoalkynyl chain moiety of the heteroarylalkynyl group may be optionally substituted as defined above for the nalynyl chain. The rosin alkyl group is as defined above. Alkyl group, substituted by one or more hydroxyl groups. ''Analgesic method'' means that under normal circumstances, the pain will be painful in response to the stimulus. 128409 •38- 200836743 in. "feeling abnormality" Innocent knowledge, such as stress or light contact, is perceived as a symptom of extreme pain. : 'Prodrugs' are intended to mean compounds that can be converted to the biologically active compounds of the invention under physiological conditions or by solvolysis. "二乌达匕, Hif

藥物&quot;一詞係指本發明化合物之代謝先質，其係為藥學上可 接文。雨體藥物當被投予有需要之病患時可為不活性，伸 在活體内被轉化成本發明之活性化合物。前體藥物典型: 係於活體内迅速地轉變，而產生本發明之母體化合物，例 如經由在血液中水解。前體藥物化合物經常在哺乳動物生 物體中提供溶解度、組織相容性或延遲釋出之優點（參閱 BUndgard，H.，前體藥物之設計（1985)，7_9, 21_2/(e1^_ Amsterdam))。前體藥物之討論係提供於ffiguchi，τ,等人，&quot;前體 藥物作為新穎傳輸系統&quot;，A.cs•論集系列，第_，盥：物 設計中之生物可逆㈣，Edward B.RQehe、㈣，美國醫藥協 會與Pergamon出版社，1987，此兩者均全部併於本文供參考。 ”前體藥物&quot;-詞亦意謂包括任何共價結合之载體，當此 種前體藥物被投予哺乳動物病患時，其會在活體内釋:本 發明之活性化合物。本發明化合物之前體藥物可藉由改變 存在於本發明化合物上之官能基而製成，其方式係致使此 等改質物係被分裂，無論是在例行操作中或於活體内，成 為本發明之母體化合物，藥物包括本發明之化合物， 其中經基、胺基或疏基係結合至任何基團，當本發明化合 物之前體藥物被投予哺乳動物病患時，其會個別分裂以形 128409 -39- 200836743 成自由態羥基、自由態胺基或自由態巯基。前體藥物之每 例包括但不限於本發明化合物中之醇官能基之酷酸西旨、; 酸醋及苯甲酸醋衍生物，或胺官能基之醯胺衍生物等。 於本文中所揭示之發明亦意謂涵蓋式⑴之所有藥學上可 接受之化合物係以同位素方式標識，其方式是使二或多個 原子被具有不同原子質量或質量數之原子置換。可被併入 所揭示化合物中之同位素之實例包括氫、碳、氮、氧、磷、 氟’氯及碘^如個別為^，^，^，％，^，％、％ l7〇，18〇,31p，32p，35s，18F，36ci i 。 ，，， ， I此專放射性標識 化合物可用以幫助測定或度量化合物之有效性，例如藉由 特徵雲定仙在鈉通道上之位置或模式，或對作用在納通 道上之藥理學上重要位置之結合親和力。某些以同位素方 ^票識之式（1)化合物’例如併人放射性同位素者，可用於 藥物及/或受質組織分佈研究。放射性同位素氚，咅即3H: 與碳-Μ ’意即14C，繁於其易於併入與立即偵測裝置，故 特別可用於此項目的。 :較重質同位素取代’譬如氣，意即2H，可提供由於較 大代谢安定性所造成之某些治療利 ^ # ^ 4皿例如增加之活體内 +生期或降低之劑量需要量’且因此在— 佳。 一 h况中可能較 以陽電子發射同位素取代，譬如丨丨i 8 可田从θ F、150及13Ν， 用於…發射表面形態(ΡΕΤ)研究，以檢驗受質受體佔 读。以同位素方式標識之式⑴化合物 蓺去Ρ, 物了一般性地藉熟諳此 食耆已知之習用技術或藉類似如 文陳迹之實例與製備中 128409 -40- 200836743 所述之方法Μ吏用適當以同位素方式標識之試劑替代先前 所採用之未經標識試劑而製成。 於本文中所揭示之發明亦意欲涵蓋所揭示化合物之活體 内代謝產物。此種產物可由於例如所投予化合物之氧化作 用、還原作用、水解作用、醯胺化作用、醋化作用等所造 成，主要是由於酵素過程。因此’本發明係包括藉由一種 過私所產生之化合物，其包括使本發明之化合物與哺乳動 物接觸，歷經-段足以產生其代謝產物之時間。此種產物 典型上係以下述方式確認’將本發明之放射性標識化合物 以可偵測劑量投予動物’譬如大白鼠、老鼠、天竺鼠、猴 子，或技予人類，允許足夠時間發生新陳代謝作用，並自 尿液、血液或其他生物試樣單離其轉化產物。 &quot;安定化合物&quot;與&quot;安定結構&quot;係意欲表示一種化合物其 足夠強健而自反應混合物中留存著，單離至有用純度及 調配成有效治療劑。 &quot;哺乳動物”包括人類，與家中動物，譬如實驗室動物與 家庭寵物（例如貓、狗、豬、牛、綿羊、山羊、馬、兔子 及非家中動物，譬如野生動物等。 k用或視炀況係意謂隨後描述之事件或狀況可以 或可以不發生，且說明文係包括其中該事件或狀況發生之 情況及其中未發生之情況。例如”視情況經取代之芳基&quot;係 意謂芳基可以或可以不經取代，且說明文、 芳基與未具有取代之芳基。當官能基係被描述二= 取代”，且接著於官能基上之取代基亦”視情況經取代，，等等 128409 -41 - 200836743 此種迭代係被限制為五次。 載劑或稀釋劑”係包括但不限 時，對本發明之目的而言 ”藥學上可接受之賦形劑 於任何佐劑、載劑、賦形劑、 J 助/瓜劑、增甜劑、稀釋劑、 防腐劑、染料/著色劑、矯味择 门木g強剡、界面活性劑、潤濕劑、 分散劑、懸浮劑、安定劑、 等滲劑、溶劑或乳化劑，其已 被美國食品藥物管理局許可為可接受供使用於人類或家畜 動物。 藥學上可接受之鹽”包括酸與鹼加成鹽兩者。 ’’藥學上可接受之酸加成鹽”係指保持自由態鹼之生物有 效性與性質之鹽，其不會在生物學上或在其他方面是不期 望的，且其係與無機酸類及有機酸類形成，該無機酸類譬 如但不限於鹽酸、氫溴酸、硫酸、硝酸、磷酸等，該有機 酸類譬如但不限於醋酸、2,2-二氣醋酸、己二酸、海藻酸、 抗壞血酸、天門冬胺酸、苯磺酸、苯甲酸、‘乙醯胺基苯 曱酸' 樟腦酸、樟腦-10-磺酸、癸酸、己酸、辛酸、碳酸、 桂皮酸、檸檬酸、環己烷胺基磺酸、十二基硫酸、乙烧^ 一石只酸、乙烧石黃酸、2-·基乙烧石黃酸、甲酸、反丁稀二酸、 半乳糖二酸、龍膽酸、葡庚糖酸、葡萄糖酸、葡萄糖酸酸、 楚胺酸 '戊二酸、2-酮基-戊二酸、甘油構酸、乙醇酸、馬 尿酸、異丁酸、乳酸、乳糖酸、月桂酸、順丁稀二酸、頻 果酸、丙二酸、苯乙醇酸、甲烷磺酸、半乳糖二酸、莕 二磺酸、苯-2-磺酸、1-羥基-2-茶曱酸、菸鹼酸、油酸、乳清 酸、草酸、棕櫚酸、雙羥莕酸、丙酸、焦麩胺酸、丙酮酸、 柳酸、4-胺基柳酸、癸二酸、硬脂酸、琥珀酸、酒石酸、 128409 -42- 200836743 氰酸、對-甲笨磺酸、三敦醋酸、十一烯酸等。 藥學上可接受之鹼加成鹽”係指保持自由態酸之生物有 效|± 14丨生貝之鹽，其不會在生物學上或在其他方面是不期 望的此等鹽係製自添加無機鹼或有機鹼至自由態酸。衍 生自無機鹼之鹽，包括但不限於鈉、鉀、鋰、銨、鈣、鎂、 鐵、辞、銅、蟲' 铭鹽等。較佳無機鹽為銨、納、卸、轉 及錤鹽。衍生自有機驗之鹽，包括但不限於以下之鹽，一 級、二級及三級胺自，經取代胺_，包括天然生成之經取 代胺類、環狀胺類及鹼性離子交換樹脂，譬如氨、異丙胺、 二甲胺、二乙胺、三乙胺、三丙胺、二乙醇胺、乙醇胺、 甲月女乙醇2-_甲胺基乙醇、2_二乙胺基乙醇、二環己基 胺、離胺酸、精胺酸、組胺酸、咖啡鹼、普魯卡因、海巴 胺：膽鹼、甜菜鹼、苄苯乙胺、苄星(―)、乙二胺、 :萄糖胺、甲基葡萄糖胺、可可鹼、三乙醇胺、丁三醇胺、 嘌呤、六氫吡啡、$氫吡啶、队乙基六氫吡啶、聚胺樹脂 f。特佳有機鹼為異丙胺、二乙胺、乙醇胺、三甲胺、二 環己基胺、膽驗及咖啡驗。 ^ ^ 、’°曰曰化作用會產生本發明化合物之溶劑合物。於 本文中使用之&quot;溶劑合物&quot;一詞係指包含一或多個本發明化 合物分子與-或多個溶劑分子之聚集體。溶劑可為水，於 、種h況巾☆劑合物可為水合物。或者，溶劑可為有 :劑1此’本發明化合物可以水合物存在，包括單水合 、一水合物'半水合物、倍半水合物、三水合物 s物等，以及其相應之溶劑化合形式。本發明化合物可為 128409 -43 - 200836743 真實溶劑合物，而在其他情況中，本發明化合物可僅只曰 保留殺偶發之水或水加上一部份偶發溶劑之混合物。 ☆西藥組合物”係指本發明化合物與此項技藝中一 又用於傳輸生物活性化合物至浦乳動物例如人類之媒質之 :方。此種媒質包括所有供其使用之藥學上可接受之載劑、 稀釋劑或賦形劑。 a…療上有效量’’係指本發明化合物之量當其被投予 礼動物，較佳為人類時，足以在哺乳動物較佳為人類中達 t鈉通道所媒介疾病或症狀之治療，如下文定義。構成” =上有效量&quot;之本發明化合物量，係依化合物、症狀及其 厫性’投樂方式’以及欲被治療哺乳動物之年齡而改變， =可例行性地由—般熟諳此藝者關於其自有知識 内容而決定。 1 丁 =本文中使用之，，進行治療&quot;或，，治療作業&quot;係涵蓋在具 吾人感興趣疾病或症狀之哺乳動物中較佳為人類， 吾人感興趣之疾病或症狀，且包括： α。、 哺或症狀發生於哺乳動物中，特別是當此種 .·丨心、β亥症狀，但尚未被診斷為具有該疾病時； (u)抑制疾病或症狀，意即遏制其發展； ㈣舒解疾病或症狀’意即造成此疾病或症狀之復原； W》咸輕由於此疾病或症狀所造成之病徵，意即減輕疼 =而未著Μ所從屬之疾病或症狀。於本文中使用”疾病” 兵’症狀”術語可交換地使用’或可為不同，在於該特定病 128409 • 44 - 200836743 :或症狀可能未具有已知病因劑(以致尚未研究出病因 予)’且其因此尚未被認為是疾病’而僅為不期望之症狀或 被候H中或多或少之特定病徵組合已被臨床家確認。 本發明化合物或其藥學上可接受之鹽可含有一或多個不 對稱中心’且因此可獲致對掌異構物、非對映異構物及其 他立體異構形式，其可以絕對立體化學為觀點，被定義為 ⑻-或⑻-，或對胺基酸為（D&gt;《(L)_。本發明係意謂包括所 有可此之異構物’以及其外消旋與光學上純形式。光學活 與（-WR)-與⑻-或叫與(L&gt;異構物可使用對掌性合成 單4或對草性5式劑製成，或使用習用技術解析，例如層析 與分級結晶。製備/單離個別對掌異構物之習用技術，包括 自適當光學上純先質之對掌性合成，或外消旋物（或鹽或衍 生物之外消旋物)之解析’使用例如對掌性高壓液相層析法 (HPLC)。當本文中所述之化合物含有烯烴雙鍵或其他幾何 不對稱中〜時’且除非另有指定，否則此等化合物係意欲 i 匕括E與Z幾何異構物。同樣地，所有互變異構形式亦意欲 被包含在内。 立體異構物係指由相同原子組成，藉相同鍵結結合， 2 〃、有不同二次兀結構之化合物，其係不可交換。本發明 意欲涵蓋各種立體異構物及其混合物，且包括”對掌異構物，， /、係扣兩種立體異構物，其分子係為彼此不可重疊鏡像。 互變異構物”係指質子從分子之一個原子移轉至相同分 子之另個原子。本發明包括任何該化合物之互變異構物。 亦在本發明範圍内者為式（I)之中間化合物，及前文所提 128409 •45- 200836743 及物種之所有多晶型物，與其結晶型。 f 於本文中使用之化學命名擬案與結構圖係為LU RA C·命 名系統之修正形式，使用ACD/命名9.07版軟體程式及/或化 學製圖（ChemDraw) ι〇·〇版軟體命名程式，其中本發明化合物 係於本文中稱為中央核心結構（意即喳唑啉酮或稠合嘧啶 酮結構）之衍生物。對本文所採用之複雜化學名稱，取代基 係在其所連接基團之前被指稱。例如，環丙基乙基係包含 乙基主鏈’具有環丙基取代基。在化學結構圖中所有鍵結 均被確認，惟一些被假定結合至足夠氫原子以完成價鍵之 碳原子除外。 因此 ，例如，式⑴化合物，其中 Q 為苯基，η為0，R2 為丁基，且R3為4-[(2-經基-3-苯氧基丙基）胺基]苯基；意即下 式化合物··The term &quot;drug&quot; refers to the metabolic precursor of a compound of the invention which is pharmaceutically acceptable. The rain medicine may be inactive when administered to a patient in need thereof, and is converted into an active compound of the invention in vivo. Prodrugs are typically: rapidly converted in vivo to produce the parent compound of the invention, e.g., via hydrolysis in blood. Prodrug compounds often provide solubility, tissue compatibility, or delayed release advantages in mammalian organisms (see BUndgard, H., Design of Prodrugs (1985), 7_9, 21_2/(e1^_Amsterdam) ). The discussion of prodrugs is provided in ffiguchi, τ, et al., &quot;Prodrugs as a novel delivery system&quot;, A.cs• series, _, 盥: bioreversible in object design (IV), Edward B. RQehe, (d), American Medical Association and Pergamon Press, 1987, both of which are incorporated herein by reference. "Prodrug" is also meant to include any carrier that is covalently bound, and when such a prodrug is administered to a mammalian patient, it will be released in vivo: the active compound of the invention. Compound prodrugs can be made by altering the functional groups present on the compounds of the invention in such a way that the modified systems are cleaved, either in routine operation or in vivo, as the precursor of the present invention. The compound, the drug includes the compound of the present invention, wherein the group, the amine group or the thiol group is bonded to any group, and when the compound of the present invention is administered to a mammalian patient, the individual compound is split to form 128409-39. - 200836743 is a free-standing hydroxyl group, a free-state amine group or a free-state sulfhydryl group. Each of the prodrugs includes, but is not limited to, the acid-functional group of the alcohol functional group in the compound of the present invention; acid vinegar and benzoic acid vinegar derivatives, Or a amide derivative of an amine functional group, etc. The invention disclosed herein also means that all pharmaceutically acceptable compounds encompassing formula (1) are identified isotopically by two or more Subunits are replaced by atoms having different atomic mass or mass numbers. Examples of isotopes that can be incorporated into the disclosed compounds include hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine 'chlorine, and iodine^, such as ^, ^, ^, %,^,%,% l7〇,18〇,31p,32p,35s,18F,36ci i . , , , , I This radioactive labeling compound can be used to help determine or measure the effectiveness of a compound, for example by a characteristic cloud The position or mode of Dingxian on the sodium channel, or the binding affinity for the pharmacologically important position acting on the nanochannel. Some of the compounds of formula (1), such as the radioisotope, are known as isotopes. It can be used for the study of drug and/or matrix distribution. The radioisotope 氚, ie 3H: and carbon-Μ' means 14C, which is easy to be incorporated into the immediate detection device, so it can be especially used in this project. The heavier isotopic substitution '譬如气, meaning 2H, can provide some treatment benefits due to greater metabolic stability, such as increased in vivo + birth or reduced dose requirements' and therefore In — good. It may be replaced by a positive electron emission isotope, such as 丨丨i 8 can be used from θ F, 150 and 13 Ν, for ... emission surface morphology (ΡΕΤ) study to test the acceptor receptor read. Isotopically identified formula (1) The compound is deuterated and is generally replaced by a conventionally known technique known in the art or by a method similar to that described in the example of 128409-40-200836743, using an appropriately labeled isotope-labeled reagent. The previously disclosed invention is also prepared using the unlabeled reagents. The invention disclosed herein is also intended to encompass in vivo metabolites of the disclosed compounds. Such products may be oxidized, reduced, hydrolyzed, for example, by administration of the compound. , amide amination, acetification, etc., mainly due to the enzyme process. Thus, the invention includes a compound produced by a smuggling comprising contacting a compound of the invention with a mammal for a period of time sufficient to produce its metabolite. Such products are typically identified as 'injecting the radiolabeled compound of the invention into the animal at a detectable dose, such as a rat, a mouse, a guinea pig, a monkey, or a human, allowing sufficient time for metabolism, and The urine, blood or other biological sample is isolated from its conversion product. &quot;Stabilization Compound&quot; and &quot;Stabilization Structure&quot; are intended to indicate that a compound is sufficiently robust to survive from the reaction mixture, to a useful purity and to be formulated into an effective therapeutic agent. &quot;Mammals&quot; include humans, and domestic animals, such as laboratory animals and family pets (such as cats, dogs, pigs, cows, sheep, goats, horses, rabbits, and non-domestic animals, such as wild animals, etc.)炀 系 意 意 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后 随后The aryl group may or may not be substituted, and the aryl group and the unsubstituted aryl group are described. When the functional group is described as two = substituted, and the substituent on the functional group is also replaced as appropriate ,, etc. 128409 -41 - 200836743 This iteration is limited to five times. Carrier or diluent" includes, but is not limited to, for the purposes of the present invention "pharmaceutically acceptable excipients in any adjuvant" , carrier, excipient, J auxiliary / melon agent, sweetener, thinner, preservative, dye / coloring agent, flavoring selected wood, strong surfactant, surfactant, wetting agent, dispersing agent, suspending agent Stabilizer Isotonic agents, solvents or emulsifiers which have been approved by the U.S. Food and Drug Administration to be acceptable for use in humans or livestock animals. Pharmaceutically acceptable salts include both acid and base addition salts. ''Pharmaceutical "Acceptable acid addition salt" means a salt which retains the biological effectiveness and properties of the free base, which is not biologically or otherwise undesirable, and which is formed with inorganic acids and organic acids, The inorganic acid such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., such as but not limited to acetic acid, 2,2-diacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid , benzenesulfonic acid, benzoic acid, 'acetamidobenzoic acid' camphoric acid, camphor-10-sulfonic acid, citric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclohexane aminosulfonic acid , 12-base sulphuric acid, sulphur-burning ^ one stone only acid, sulphuric acid, 2-ethyl hexyl sulphate, formic acid, succinic acid, galactose diacid, gentisic acid, glucoheptonic acid , gluconic acid, gluconic acid, cholic acid 'glutaric acid, 2-keto-penta Acid, glycerol acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, cis-butyl diacid, frequency acid, malonic acid, phenylglycolic acid, methanesulfonic acid, galactose diacid , stilbene disulfonic acid, benzene-2-sulfonic acid, 1-hydroxy-2-thetaic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, hydroxamic acid, propionic acid, pyroguanamine Acid, pyruvic acid, salicylic acid, 4-aminosarnic acid, azelaic acid, stearic acid, succinic acid, tartaric acid, 128409-42-200836743 cyanic acid, p-formyl sulfonic acid, three acid acetic acid, undecene Acids, etc. pharmaceutically acceptable base addition salts" means that the organisms that retain the free acid are effective | ± 14 丨 丨 之 salt, which is not biologically or otherwise undesirable. Self-addition of inorganic or organic bases to free acids. Salt derived from inorganic bases, including but not limited to sodium, potassium, lithium, ammonium, calcium, magnesium, iron, rhodium, copper, insects, etc. Preferred inorganic salts are ammonium, sodium, unloaded, converted and sulfonium salts. Salts derived from organic tests, including but not limited to the following salts, primary, secondary and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, For example, ammonia, isopropylamine, dimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, methyl female ethanol 2-methylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine , aminic acid, arginine, histidine, caffeine, procaine, seabamine: choline, betaine, benzidine, benzathine (-), ethylenediamine, :glucosamine, Methyl glucosamine, theobromine, triethanolamine, succinylamine, hydrazine, hexahydropyridol, hydrogen pyridine, quinone hexahydropyridine, polyamine resin f. The most preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, biliary test and coffee test. ^ ^ , '°曰曰 will produce a solvate of the compound of the invention. The term &quot;solvate&quot; as used herein refers to an aggregate comprising one or more molecules of the invention and/or a plurality of solvent molecules. The solvent may be water, and the composition may be a hydrate. Alternatively, the solvent may be: agent 1 such 'the compound of the invention may be present as a hydrate, including monohydrate, monohydrate' hemihydrate, sesquihydrate, trihydrate s, and the like, and corresponding solvated forms thereof . The compounds of the invention may be from 128409 to 43 to 200836743 true solvates, while in other instances, the compounds of the invention may only contain a mixture of water or water plus a portion of the incidental solvent. ☆ Western medicine composition means a compound of the present invention and one of the techniques used in the art for transporting a biologically active compound to a milking animal such as a human. The medium includes all pharmaceutically acceptable carriers for its use. Agent, diluent or excipient. a...therapeutically effective amount '' means the amount of the compound of the invention when it is administered to a ceremonial animal, preferably a human, sufficient to achieve t sodium in a mammal, preferably a human. The treatment of a disease or condition transmitted by a channel, as defined below. The amount of the compound of the invention that constitutes "the effective amount" is based on the compound, the symptoms and the sputum's 'preparation method' and the age of the mammal to be treated. Change, = can be routinely determined by the artist's own knowledge content. 1 D = As used herein, the treatment &quot;or, treatment operation&quot; is intended to encompass diseases or symptoms of human interest, which are of interest to a mammal having a disease or condition of interest to us, and includes: α. , or the symptoms occur in mammals, especially when such symptoms are not diagnosed as having the disease; (u) inhibiting the disease or symptoms, that is, curbing its development; "Resolving a disease or symptom" means causing the recovery of the disease or condition; W" is a symptom caused by the disease or symptom, which means reducing the pain = without the disease or symptom of the disease. As used herein, the term "disease" is used interchangeably or 'may be different, in that particular disease 128409 • 44 - 200836743 : or the symptoms may not have a known causative agent (so that the cause has not been studied) And it has therefore not been considered a disease' and only the undesired symptoms or the combination of specific symptoms more or less in the H has been confirmed by the clinician. The compound of the present invention or a pharmaceutically acceptable salt thereof may contain one or Multiple asymmetric centers' and thus can be obtained as palmoisomers, diastereomers and other stereoisomeric forms, which can be defined as (8)- or (8)-, or by amino groups, from the standpoint of absolute stereochemistry. The acid is (D&gt; "(L)_. The invention is meant to include all such isomers" as well as its racemic and optically pure forms. Optically active (-WR)- and (8)- or (L&gt; isomers can be prepared by using the palm-forming synthetic 4 or the grassy formula 5, or using conventional techniques such as chromatography and fractional crystallization. Preparation/single separation of individual palm isomers , including the palm-like synthesis from the pure optically pure precursor, or The resolution of the racemate (or the racemate of the salt or derivative) is used, for example, in the palm-top high pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other geometric asymmetry <RTIgt; </ RTI> and unless otherwise specified, such compounds are intended to include both E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. Stereoisomer refers to the same atom Compositions, by the same bonding, 2 〃, compounds having different secondary fluorene structures, which are not interchangeable. The invention is intended to cover various stereoisomers and mixtures thereof, and includes "the palmomers, /, Tethering two stereoisomers whose molecular systems are non-superimposable mirror images of each other. "Tautomers" refers to the transfer of a proton from one atom of a molecule to another atom of the same molecule. The invention encompasses the intermutation of any such compound Also within the scope of the invention are intermediate compounds of formula (I), and all polymorphs of the above mentioned species 128409 • 45-200836743 and species, and their crystalline forms. f Chemical nomenclature used herein case And the structure diagram is a modified form of the LU RA C. naming system, using the ACD/naming version 9.07 software program and/or the chemical drawing (ChemDraw) ι〇·〇 version software naming program, wherein the compound of the present invention is referred to herein as a derivative of a central core structure (ie, an oxazolinone or a fused pyrimidinone structure). For the complex chemical name used herein, a substituent is referred to before the group to which it is attached. For example, cyclopropylethyl Contains an ethyl backbone 'having a cyclopropyl substituent. All linkages are confirmed in the chemical structure diagram, except for some carbon atoms that are assumed to bind to a sufficient hydrogen atom to complete the valence bond. Thus, for example, formula (1) a compound wherein Q is phenyl, η is 0, R 2 is butyl, and R 3 is 4-[(2-yl-3-phenoxypropyl)amino]phenyl; meaning a compound of the formula:

ch3 係於本文中命名為2-丁基-3-{4-[(2-羥基_3-苯氧基丙基）胺基] 苯基}喹唑啉-4(3H)-酮。 本發明之具髏實施例 在上文發明内容中所提出本發明之各方面中，某些具體 128409 -46 - 200836743 實施例為較佳。 一項具體實施例為式（I)化合物：Ch3 is herein designated as 2-butyl-3-{4-[(2-hydroxy-3-phenoxypropyl)amino]phenyl}quinazolin-4(3H)-one. EMBODIMENT OF THE INVENTION In the various aspects of the invention set forth above in the Summary of the Invention, certain embodiments of the specific 128409-46 - 200836743 are preferred. A specific embodiment is a compound of formula (I):

^ 5 ，R1，R2及R3均如上文在發明内容中所敘述，為 其亡體異構物、對掌異構物、互變異構物或其混合物；或 ”某予上可接受之鹽、溶劑合物或前體藥物。 另一項具體實施例為如上文所示之式①化合物，其中：^ 5 , R 1 , R 2 and R 3 are as described above in the Summary of the Invention, as an exo isomer, a palmomer, a tautomer or a mixture thereof; or "a certain acceptable salt, A solvate or prodrug. Another specific embodiment is a compound of formula 1 as shown above, wherein:

為稠合芳基； 稀基、快基、_基、_烧 各R1係獨立選自包括氫、烷基、 基、A烯基、i炔基、環烷基、環烷基烷基、環烷基 埽基、環燒基快基、芳基、芳烧基、芳稀基、芳块基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R6_CN、 女6-N02、-R6-〇R5、_R6-N(R4)R5、_R6-S(〇)pR4、_R6_c(〇)R4、 火6-c(s)r4、-r6-c(r4)2c(0)r5、-R6-c(o)〇R4、-R6-0C(0)R4、 女 6-c(s)or4 、-r6-c(o)n(r4)r5 、-r6-c(s)n(r4)r5 、 女6-N(R5)C(0)R4、-R6-N(R5)C(S)R4、-R6-N(R5)C(0)0R4、 火6-n(r5)c(s)or4、-r6-n(r5)c(o)n(r4)r5、-R6-N(R5)C(S)N-(R4 )R5、_R6 -N(R5 )S(0)t R4、_R6 _N(R5 )s(0)t N(R4 )R5、 128409 -47- 200836743 -R6 -S(0)t N(R4 )R5、-R6 -N(R5 )C(=Nr5 )N(R4 )R5 及 _R6 _n(rS )_ C(N=C(R4)R5)N(R4)R5，其中各p係獨立為〇，1或2，且各t 係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳環原子一起，可 形成稠合環，選自環烷基、芳基 '雜環基或雜芳基， 而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烧基、環烷基烷基、環烷基浠基、芳基、芳烧基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烷基、烯基、炔基、函烷基、鹵烯基、^炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基…R7_N(R4)R5或 R7-N(R4)C(0)0R4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環 基烧基、雜環基烯基、雜環基炔基、雜芳基、雜 芳烧基、雜芳基烯基或雜芳基炔基可視情況被一 或多個取代基取代，取代基選自包括烷基、烯基、 炔基、_基、_烷基、！I烯基、齒炔基、視情況 經取代之環烷基、視情況經取代之環烷基烷基、 128409 -48- 200836743 視情況經取代之環烷基烯基、視情況經取代之環 烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取 代之芳快基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜環基烯 基、視情況經取代之雜環基炔基、視情況經取代 之雜芳基、視情況經取代之雜芳烷基、視情況經 取代之雜芳基烯基、視情況經取代之雜芳基炔基、 -R6-CN ^ -R6-N〇2 ^ .R6-OR5 . -R6-0C(0)R4 . -R6.〇S(〇)2R4 、-R6，C(〇)r4、-R6-C(0)0R4、-R6-C(0)N(R4)R5、 -R6-N(R4)R5 . -R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(0)0R4 . •R6 -N(R5 )C(0)N(R4 )R5 、 -R6-N(R5 )S(0)tR4 、 -R6 -N[S(〇)t R4 ]2 . -R6 .N(R5 )C(=NR5 )N(R4 )R5 x .r6 .N(r5 y C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)- C(0)0R4、-r6-n(R5)-R7_n(R4)R5、-R6-N=C(OR4)R5、 -R6-N=C(R4)R5、_R6_N(R5)-R6_〇R5、-R6_S(〇)pR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇, 1或2，且各 t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 經烧基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 128409 -49- 200836743 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式（I)化合物，其中： η為1至4 ;Is a fused aryl group; a dilute group, a fast group, a _ group, a _ group, each R1 is independently selected from the group consisting of hydrogen, alkyl, benzyl, alkenyl, i alkynyl, cycloalkyl, cycloalkylalkyl, ring Alkyl fluorenyl, cycloalkyl radical, aryl, arylalkyl, aryl, aryl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl Base, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, _R6_CN, female 6-N02, -R6-〇R5, _R6-N(R4)R5, _R6-S(〇)pR4, _R6_c( 〇) R4, fire 6-c(s)r4, -r6-c(r4)2c(0)r5, -R6-c(o)〇R4, -R6-0C(0)R4, female 6-c( s)or4, -r6-c(o)n(r4)r5, -r6-c(s)n(r4)r5, female 6-N(R5)C(0)R4, -R6-N(R5) C(S)R4, -R6-N(R5)C(0)0R4, fire 6-n(r5)c(s)or4, -r6-n(r5)c(o)n(r4)r5,- R6-N(R5)C(S)N-(R4)R5, _R6 -N(R5)S(0)t R4, _R6 _N(R5 )s(0)t N(R4 )R5, 128409 -47- 200836743 -R6 -S(0)t N(R4 )R5, -R6 -N(R5 )C(=Nr5 )N(R4 )R5 and _R6 _n(rS )_ C(N=C(R4)R5) N(R4)R5, wherein each p-line is independently 〇, 1 or 2, and each t-series is independently 1 or 2; or two adjacent R1 groups together with the carbon ring atoms to which they are directly bonded may form Fused ring , selected from cycloalkyl, aryl 'heterocyclyl or heteroaryl, and the remaining R1 groups, if present, are as defined above; R2 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkyl , haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylindenyl, aryl, arylalkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclyl Alkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is hydrogen, alkyl, alkenyl, alkynyl, functional alkyl, haloalkenyl , alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclic, Heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl...R7_N(R4)R5 or R7-N (R4 C(0)0R4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, hetero Cycloalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroaryl The alkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, yl, _alkyl, ! Ialkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, 128409-48-200836743 optionally substituted cycloalkylalkenyl, optionally substituted ring Alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aryl radical, optionally substituted heterocyclyl, optionally Substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl , optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN^-R6-N〇2^.R6-OR5 . -R6-0C(0)R4 . R6.〇S(〇)2R4, -R6,C(〇)r4, -R6-C(0)0R4, -R6-C(0)N(R4)R5, -R6-N(R4)R5 . - R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(0)0R4 . •R6 -N(R5 )C(0)N(R4 )R5 , -R6-N(R5 ) S(0)tR4, -R6 -N[S(〇)t R4 ]2 . -R6 .N(R5 )C(=NR5 )N(R4 )R5 x .r6 .N(r5 y C(=NR5) N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)- C(0)0R4, -r6-n(R5)-R7_n(R4)R5,-R6 -N =C(OR4)R5, -R6-N=C(R4)R5, _R6_N(R5)-R6_〇R5, -R6_S(〇)pR4 and -R6-S(0)tN(R4)R5, each of which p is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkyl, alkoxy Alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally a substituted heterocyclic alkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; 128409 - 49 - 200836743 or R4 together with R5 and the nitrogen to which they are attached a substituted N-heterocyclic group or an optionally substituted N-heteroaryl group; each R6 is a direct-bonded, optionally substituted straight or branched alkylene chain, optionally substituted a chain or branched sub-alkenyl chain or an optionally substituted linear or branched decynyl chain; and R7 is a linear or branched alkylene chain, a linear or branched subalkenyl chain Or a linear or branched subalkynyl chain. As defined above for compounds of formula (I) indicated above, wherein: η is 1 to 4;

Q 〇為稠合苯基； 各R1係獨立選自包括氫、烷基、烯基、炔基、鹵基、鹵烷 基、函稀基、函炔基、環烧基、環烧基烧基、環烧基 稀基、環烧基炔基、芳基、芳烧基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、-R6 _CN、 -R6-N02、-R6-OR5、-R6-N(R4)R5、-R6-S(0)PR4、-R6-C(0)R4、 -R6 -C(S)R4、-R6 -C(R4 )2 C(0)R5、-R6 -CX〇)〇R4、-R6 _〇c(〇)r4、 -R6 -C(S)OR4、-R6 -C(0)N(R4 )R5、-R6 -C(S)N(R4 )R5、 -R6-N(R5)C(0)R4、_R6-N(R5)C(S)R4、-R6_N(R5)C(〇)〇R4、 &gt;R6-N(R5 )C(S)OR4 &gt; -R6-N(R5 )C(0)N(R4 )R5 , -R^N(R5)C(S&gt; N(R4)R5、-R6-N(R5)S(0)tR4、-R6_N(R5)s(〇)tN(R4)R5、 •R6 -S(0)tN(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 _N(R5 &gt; C(N=C(R4)R5)N(R4)R5，其中各p係獨立為〇，1或2，且各t -50- 128409 200836743 係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳環原子一起，可 形成稠合環，選自環烷基、芳基、雜環基或雜芳基， 而其餘R1基團，若存在則均如上述； R為氫、烷基、烯基、炔基、鹵烷基、画烯基、_炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜裱基炔基、雜芳基、雜芳烷基雜芳基烯基或雜芳基 快基； / R為氫、烷基、烯基、炔基、鹵烷基、幽烯基、齒炔基、 經烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 快基芳基、芳烧基、芳稀基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、·Κ7·Ν(Κ4)Κ5或 _R、n(r4)c(o)or4 ; /、令％烧基、％烧基燒基、環烧基婦基、環烧基快基、 芳基、芳烧基、芳烯基、芳炔基、雜環基、雜環 基烷基、雜環基烯基'雜環基炔基、雜芳基、雜 芳院基、雜芳基婦基或雜芳基块基可視情況被〜 或多個取代基取代，取代基選自包括烷基 、烯基、 炔基i基、鹵燒基、虐烯基、由块基、視情況 經取代之環炫基、視情況經取代之環烧基烧基、 視情況經取代之環院基烯基、視情況經取代之環 院基炔基、視情況經取代之芳基、視情況經取代 128409 51 200836743 之芳烷基、視情況經取代之芳烯基、視情況經取 代之芳炔基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜環基稀 基、視情況經取代之雜環基炔基、視情況經取代 之雜芳基、視情況經取代之雜芳烷基、視情況經 取代之雜芳基烯基、視情況經取代之雜芳基炔基、 R6 -CN、-R6 -N02、-R6 -OR5、-R6 -〇c⑼R4、_r6 〇s(〇h r4 …R6-C(〇)r4、-R6-C(0)0R4、-R6-C(0)N(R4)R5、 -R6-N(R4)R5 . -R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(0)〇R4 &gt; -R6 -N(R5 )C(0)N(R4 )R5 、 -R6 -N(R5 )S(0)t R4 、 -R6 -N[S(0)t R4 ]2、_r6 啊R5 )c(=nr5 风r4 )r5、r6 _n(r5 )_ C(=NR5)N(R4)CN - -R6-N(R5)C[=NC(0)0R4]-N(R4&gt; C(0)〇R4、_n(R5 ) r7 n(r4 )r5 r6 n=c(〇r4 )r5 -R6-N=C(R4)R5、_r6_n(r5)-r6_〇r5、_R6_s(〇)pR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇, i或2，且各 t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 罗工烧基、燒氧烧基、視情況經取代之環烧基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基； 128409 -52- 200836743 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式①化合物，其中 η為1 ;Q 〇 is a fused phenyl group; each R 1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkyl, difunctional, alkynyl, cycloalkyl, cycloalkyl , cycloalkylthio, cycloalkylalkynyl, aryl, arylalkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, Heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, -R6-N(R4)R5, -R6-S(0 ) PR4, -R6-C(0)R4, -R6 -C(S)R4, -R6 -C(R4)2 C(0)R5, -R6 -CX〇)〇R4, -R6 _〇c( 〇)r4, -R6 -C(S)OR4, -R6 -C(0)N(R4)R5, -R6 -C(S)N(R4)R5, -R6-N(R5)C(0) R4, _R6-N(R5)C(S)R4, -R6_N(R5)C(〇)〇R4, &gt;R6-N(R5)C(S)OR4 &gt; -R6-N(R5)C( 0) N(R4)R5, -R^N(R5)C(S&gt; N(R4)R5, -R6-N(R5)S(0)tR4, -R6_N(R5)s(〇)tN(R4 ) R5, • R6 - S(0) tN(R4)R5, -R6 - N(R5)C(=NR5 )N(R4 )R5 and -R6 _N(R5 &gt; C(N=C(R4)R5 N(R4)R5, wherein each p is independently 〇, 1 or 2, and each t -50-128409 200836743 is independently 1 or 2; or two adjacent R1 groups and the carbon to which they are directly attached Ring atom A fused ring may be formed, selected from cycloalkyl, aryl, heterocyclic or heteroaryl, and the remaining R1 groups, if present, are as described above; R is hydrogen, alkyl, alkenyl, alkynyl , haloalkyl, alkenyl, ethynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocycle An alkyl group, a heterocyclylalkenyl group, a heterofluorenyl alkynyl group, a heteroaryl group, a heteroaralkyl heteroarylalkenyl group or a heteroaryl group; /R is hydrogen, an alkyl group, an alkenyl group, an alkynyl group, Haloalkyl, pentoalkenyl, alkynyl, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkyl fast aryl, arylalkyl, aryl, aryl , heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, Κ7·Ν Κ4)Κ5 or _R, n(r4)c(o)or4; /, %% base, % alkyl group, cycloalkyl group, cycloalkyl group, aryl group, aryl group, aromatic Alkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl 'heterocyclylalkynyl, heteroaryl, hetero-aromatic a heteroaryl or heteroaryl block optionally substituted with ~ or a plurality of substituents selected from the group consisting of alkyl, alkenyl, alkynyl i, haloalkyl, alkenyl, by block a cyclohexyl group which may be optionally substituted, a cycloalkyl group which may be optionally substituted, a cycloalkenyl group which may be optionally substituted, a substituted alkynyl group as the case may be substituted, and an optionally substituted aryl group Substituting aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, as appropriate, in the case of 128409 51 200836743 , optionally substituted heterocyclyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroaryl Alkenyl, optionally substituted heteroarylalkynyl, R6-CN, -R6-N02, -R6-OR5, -R6-〇c(9)R4, _r6 〇s(〇h r4 ... R6-C(〇)r4, -R6-C(0)0R4, -R6-C(0)N(R4)R5, -R6-N(R4)R5 . -R6-N(R5)C(0)R4 &gt; -R6-N( R5)C(0)〇R4 &gt; -R6 -N(R5 )C(0)N(R4 )R5 , -R6 -N(R5 )S(0)t R 4, -R6 -N[S(0)t R4 ]2, _r6 啊R5 )c(=nr5 wind r4 )r5,r6 _n(r5 )_ C(=NR5)N(R4)CN - -R6-N (R5)C[=NC(0)0R4]-N(R4&gt; C(0)〇R4,_n(R5) r7 n(r4 )r5 r6 n=c(〇r4 )r5 -R6-N=C( R4) R5, _r6_n(r5)-r6_〇r5, _R6_s(〇)pR4 and -R6-S(0)tN(R4)R5, wherein each p-system is independently 〇, i or 2, and each t-series is independent Is 1 or 2; each of R4 and R5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, rotunn, anthracyl, optionally substituted cycloalkyl, optionally Substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted a heteroaryl group and optionally substituted heteroaralkyl; or R4 together with R5 and the nitrogen to which they are attached, form an optionally substituted N-heterocyclic group or an optionally substituted N-heteroaryl Each of R6 is a direct-bonded, optionally substituted linear or branched alkylene chain, optionally substituted straight or branched subalkenyl chain or optionally substituted Straight chain Times branched alkynyl chain; and R is a straight-chain or branched alkylidene chain, a straight or branched alkenylene chain or secondary linear or branched alkynyl chain views. Another specific embodiment is a compound of formula 1 as shown above, wherein η is 1;

0 〇為稠合苯基； R1為氫； r2為氫或烷基； R為芳基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、鹵基、鹵烷基、-烯基、画炔 基、視情況經取代之環烷基、視情況經取代之環烷 基烧基、視情況經取代之環炫基稀基、視情況經取代 之環烧基块基、視情況經取代之芳基、視情況經取代 之芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基烤基、視情況經取 代之雜環基块基、視情況經取代之雜芳基、視情況經 取代之雜芳絲、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、_r6_n〇2、_r6 ^r5、 -R6-oc(o)R4、_r6_os(〇)2R4、_r6_c⑼R4、_r6-c_r4、 -R6-C(0)N(R4)R5 . -R6.N(r4)r5 , -R6.N(R5)C(〇)R4 . 128409 -53 - 200836743 -R6 -N(R5 )C(0)OR4、-R6 -N(R5 )C(0)N(R4 )R5、-R6 _N(R5 )S(0)t R4 、-R6-N[S(0)tR4]2、-R6-N(R5)C(=NR5)N(R4)R5、-R6_N(R5&gt;· C(=NR5)N(R4)CN、-R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4、 -R6-N(R5)-R7-N(R4)R5、-R6_N=C(OR4)R5、-R6-N=C(R4)R5、 -R6-N(R5)-R6-〇R5、-R6-S(0)PR4 及-R6-S(〇)tN(R4)R5，其中各 p係獨立為0, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 經烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環院基烧基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N_雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷美 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鍵或分枝狀次快基鍵；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式（1)化合物，其中： η 為 1 ; '、0 稠 is a fused phenyl; R 1 is hydrogen; r 2 is hydrogen or alkyl; R is aryl, optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo Alkyl, haloalkyl, alkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cyclononyl, optionally substituted a cycloalkyl group, optionally substituted aryl, optionally substituted aryl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclic, Optionally substituted heterocyclic alkyl, optionally substituted heterocyclic base, optionally substituted heterocyclic block, optionally substituted heteroaryl, optionally substituted heteroaryl , optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, _r6_n〇2, _r6^r5, -R6-oc(o)R4, _r6_os(〇)2R4, _r6_c(9)R4, _r6-c_r4, -R6-C(0)N(R4)R5 . -R6.N(r4)r5 , -R6.N(R5)C(〇)R4 . 128409 -53 - 200836743 -R6 -N(R5 ) C(0)OR4, -R6 -N(R5 )C(0)N(R4 )R5, -R6 _N(R5 )S(0)t R4 , -R6-N[S(0)tR4]2, -R6-N(R5)C(=NR5)N(R4)R5, -R6_N(R5&gt;·C( =NR5)N(R4)CN, -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4, -R6-N(R5)-R7-N(R4 R5, -R6_N=C(OR4)R5, -R6-N=C(R4)R5, -R6-N(R5)-R6-〇R5, -R6-S(0)PR4 and -R6-S( 〇)tN(R4)R5, wherein each p-series is independently 0, 1 or 2, and each t-series is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, Alkyl, alkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted ring-based alkyl, optionally substituted aryl, optionally substituted aralkyl, Optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 and R5 and both Together with the nitrogen, an optionally substituted N-heterocyclyl or, as the case may be, a substituted heteroaryl; each R6 is a direct-bonded, optionally substituted, linear or branched sub-alkane chain, as appropriate Substituted linear or branched secondary alkenyl chain or optionally substituted straight or branched secondary fast radical ; And R7 is a straight-chain or branched alkylidene chain, a straight or branched alkenylene chain or secondary linear or branched alkynyl chain views. Another specific embodiment is a compound of formula (1) as shown above, wherein: η is 1; ',

Q 為稠合苯基； R1為氯； 128409 •54- 200836743 R2為氫或烷基； r3為苯基，視情況被―心彳轉代基取代，取代基選自包 括炫基、稀基、你其、„ 、土 _基、_烷基、鹵烯基、鹵炔 基視月況^取代之環烧基、視情況經取代之環烧基 録、視情況經取代之我基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基稀I、視情況經取 代之雜環基快基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、HNC&gt;2、^6_qr5、 -R6-0C(0)R4、-r6-0S(0)2R4、r6-C(〇)r4、_r6_c(〇)〇r4、 -R6-C(0)N(R4)R5 &gt; -R6-N(R4)R5 . -R6.N(R5)C(〇)R4 λ .Re.^K5y C(0)(m4 、_r6_n(r5)c(〇)n(r4)r5 、_R6 •叫R5 执叫 r4 、 i. -R6-N[S(0)tR4]2、-R6_N(R5)C(=NR5)N(R4)R5、-R6-N(R5)· C(=NR5 )N(R4 )CN &gt; -r6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R -N(R )-R7-N(R4)R5 - -R6-N=C(OR4 )R5 . -R6-N=C(R4 )R5 &gt; -R6_N(R5)-R6-0r5、KS(0)pR4ns(〇)tN(R4)R5，其中各 P係獨立為0, 1或2，且各t係獨立為1或2; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基烷基、 羥烧基、烧氧烧基、視情況經取代之環烧基、視情況 經取代之環烧基烧基、視情況經取代之芳基、視情況 經取代之芳烧基、視情況經取代之雜環基、視情況經 128409 -55- 200836743 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 ^ R為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次快基鏈。 另一項具體實施例為如上文所示之式①化合物，其中： η為1 ;Q is a fused phenyl group; R1 is chlorine; 128409 • 54- 200836743 R2 is hydrogen or an alkyl group; r3 is a phenyl group, optionally substituted by a fluorene group, and the substituent is selected from the group consisting of a leuco group, a dilute group, Your „ , ,                         Optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aryl, optionally substituted aralkenyl, optionally substituted alkynyl, optionally substituted Heterocyclic group, optionally substituted heterocyclic group, optionally substituted heterocyclic group I, optionally substituted heterocyclic group, optionally substituted heteroaryl, optionally Substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, HNC&gt;2, ^6_qr5, -R6-0C(0)R4, -r6- 0S(0)2R4, r6-C(〇)r4, _r6_c(〇)〇r4, -R6-C(0)N(R4)R5 &gt; -R6-N(R4)R5 . -R6.N(R5 )C(〇)R4 λ .Re.^K5y C(0)(m4 , _r6_n(r5)c(〇)n(r4)r5 , _R 6 • Called R5 to call r4, i. -R6-N[S(0)tR4]2, -R6_N(R5)C(=NR5)N(R4)R5, -R6-N(R5)·C(= NR5 )N(R4 )CN &gt; -r6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R -N(R )-R7-N(R4 R5 - -R6-N=C(OR4)R5 . -R6-N=C(R4)R5 &gt; -R6_N(R5)-R6-0r5, KS(0)pR4ns(〇)tN(R4)R5, Wherein each P is independently 0, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, and oxygenated An alkyl group, optionally substituted cycloalkyl group, optionally substituted cycloalkyl group, optionally substituted aryl group, optionally substituted aryl group, optionally substituted heterocyclic group, a heterocyclylalkyl group, optionally substituted heteroaryl group, and optionally substituted heteroarylalkyl group, substituted by 128409-55-200836743; or R4 together with R5 and the nitrogen to which they are attached Substituted N-heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct-bonded, optionally substituted, straight or branched alkylene chain, optionally substituted straight chain Or branched sub-alkenyl chains or optionally substituted straight chains or Dendritic times alkynyl chain; and ^ R is a linear or branched alkylidene chain, a straight or branched alkenylene chain or secondary linear or branched chain group times faster. Another specific embodiment is a compound of formula 1 as shown above, wherein: η is 1;

Q 為稠合苯基； R1為氫； R2為氫或烷基； R為苯基，視情況被一或多個取代基取代，取代基選自包 \, 括烧基、_基、鹵烧基、-R6 -CN、-R6 -OR5、-R6 _〇c(0)R4、 -R6-0S(0)2R4、-R6-C⑼0R4、_R6_c(〇)n(r4)r5、_R卜n(r4)r5、 -R6-N(R5)C(〇)R4、-R6-N(R5)C(〇)〇R4、_R6-N(r5)c(〇)n(R4)r5 、-R6-N[S(0)tR4]2 、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 、 -R6 -N(R5 )C(=NR5 )N(R4 )CN 、 -R6 -N(R5 )-R7 -N(R4 )R5 、 -R6-N(R5)C[=N^0R4]-N(R4)-C(0)0R4、_r6-N=^^^ -R6-N=C(R4)R5、-R6_N(R5)-R6-〇r5 及 _R6-S(〇)tN(R4)R5，其中 各p係獨立為0, 1或2，且各t係獨立為1或2 ; 128409 -56- 200836743 各R4與R5係獨立選自包括氫、烷基、_烷基、視情況經取 代之芳基、視情況經取代之雜環基、視情況經取代之 雜環基烧基及視情況經取代之雜芳基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之n-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次稀基鏈或直 鍵或分枝狀次快基鍵。 另一項具體實施例為如上文在發明内容中所提出之式⑴ 化合物，其係選自包括： 2· 丁基各(4_甲氧苯基）p奎峻琳·4(3Η)_酮； 4-(2-丁基-4-酮基喹唑啉-3(4Η)-基）苯甲醯胺； 2-胺基苯甲酸4-(2-丁基-4-酮基喳唑啉-3(4Η)-基）苯酯； 2- [(1_甲氧基亞戊基）胺基]苯甲酸4-(2_ 丁基-4-酮基喳唑啉 -3(4Η)-基）苯酯； (1Ζ)-Ν-[4-(2-丁基-4-酮基喳唑啉_3(4Η)_基）苯基]戊亞胺酸甲酯； 三氟甲烷磺酸4-(2-丁基-4-酮基喹唑啉-3(4Η)-基）苯酯； 3- (4-胺基苯基）-2-丁基峻唾淋-4(311)-酉同； 4- (2-丁基-4-酮基喳唑啉-3(4Η)-基）苯磺醯胺； 4-(2•丁基-4-酮基喹唑啉-3(4Η)-基）苯甲酸甲酯； 4_(2_丁基-4-酮基喳唑啉-3(4Η)-基）苯甲酸； 3-(4-溴苯基）-2-丁基喳唑啉-4(3Η)-酮； 128409 -57- 200836743 3-(3-胺基苯基）_2_丁基喹唑啉·4(3Η&gt;酮； 1·[4-(2-丁基冰酮基喹唑啉-3(4Η)-基）苯基]脲； 2_丁基-3-[4_(甲胺基）苯基]喹唑啉-4(3Η)-酮； 3-(4-胺基苯基）-2-甲基喳唑啉-4(3Η&gt;酮； 3-(3-胺基苯基）-2-甲基喳唑啉-4(3Η)-酮； 3-(4-胺基苯基）-2-戊基喳唑啉-4(3Η&gt;酮； 3_(4·胺基苯基）-2-丙基喹唑啉-4(3Η)-酮； 2-丁基-3-[4七比咬-2-基胺基）苯基]ρ奎唾淋-4(3Η)-酮； 2·丁基-3-(4-嗎福琳-4-基苯基）邊唾琳-4(3H)-S同； 2- 丁基-3-(4-氟苯基）喳唑啉-4(3H)-酮； 3- (2-胺基苯基）-2-丁基喳唑啉_4(3H)_酮； 1- [4-(2-丁基-4-酮基喳唑啉-3(4H)·基）苯基]胍； 2- 丁基-3-(4-氯苯基）喹唑啉-4(3H)-酮； H4-(2-丁基-4-酮基喹唑啉-3(4H&gt;基）苯基]_3_氰胍； 3·{[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]胺基}四氫吡咯-1· 羧酸第三-丁酯； 2-丁基-3-[4-(四氫ρ比洛-3-基胺基）苯基]峻峻p林-4(3H)-K ; 2-丁基各(4-{[2-(二甲胺基）乙基]胺基}苯基）喹唑啉-4(3H)-酮； 2-丁基-3-[4-(4-甲基六氯ρ比呼-1-基）苯基]p奎峻琳-4(3H)-嗣； 2- 丁基-3·(4-六氯批呼-1-基苯基）峻嗤淋-4(3H)-S同； 3- (4-胺基-2,5-二甲基苯基）-2-丁基喹唑啉-4(3H)-酮； 3- (4-胺基苯基）·2_乙基p奎唾淋-4(3H)-嗣； 4- (2-丁基-4-酮基喹唑啉-3(4H)-基）苯甲腈； 3-(4-胺基-2,3,5,6-四曱基苯基）-2-丁基喳唑啉-4(3H)-酮； 128409 -58 - 200836743 3-(4-胺基-2,5-二氣苯基）·2-丁基p奎嗤琳-4(3H)-酮； 3-(4-溴基-2-氟苯基）-2-丁基p奎唾琳-4(3H)-酮； 3-[4-(胺基甲基）苯基]-2-丁基喹唑啉-4(3H)-酮； [4_(2_丁基_4·酮基喹唑琳-3(4H)-基）爷基]胺基甲酸第三丁酯； 3-(4-漠基-2-氯苯基）-2-丁基峻σ坐琳-4(3H)-酮； 3-[4-溴基-2-(三氟甲基）苯基]-2-丁基喳唑啉-4(3H)-酮； 3-(4溴基-2,6-二氟苯基）-2-丁基p奎唾琳-4(3H)-酮； 3-(4-漠、基-2-甲基苯基）-2_丁基峻唾琳-4(311)-酮； (_ 3-(4-漠基-2,6-二甲基苯基）-2-丁基p奎σ坐淋_4(3H)-S同； 2-丁基-3-(2-氯基-4-嗎福啉-4-基苯基）喹唑琳-4(3H&gt;酮； 2·丁基_3-[4-嗎福啉-4-基-2-(三氟甲基）苯基]4唑啉-4(3H)-酮； 2-丁基-3-(2,6-二氟-4-嗎福啉-4-基苯基）喳唑啉-4(3H)-酮； 2-丁基-3-(2-甲基-4-嗎福淋-4-基苯基）喳唑琳-4(3H)-酮； 2-丁基_3-(2,6-二甲基冰嗎福啉-4-基苯基）邊唑啉·4(3Η)-ϊ同； 2-丁基-3-(2-亂基-4-嗎福淋-4-基苯基）τί奎u坐Ρ林_4(3Η)_闕； 2- 丁基-3-(4-六氫说咬-1-基苯基 &gt;奎唑琳_4(3Η)_酮； i 2_丁基-3·[4_(六氫p比咬-3-基胺基）苯基p奎唾琳_4(3H)_酮； 3- [4-胺基-3-(三氟甲基）苯基]-2-丁基p奎唑琳-4(3H)·酮； 3-[4-胺基-2-(三氟甲基）苯基]-2-丁基喳唑p林-4(3H)·酮； 2-丁基-3-{4-[(2-羥基-3-苯氧基丙基）胺基]苯基}p奎唑啉·4(3Η)_ 酮； 2-丁基-3-{4-[2-(苯氧基曱基）嗎福琳_4_基]苯基}ρ奎唑4 4(3Η)- 酮； 2-丁基-3-(4-{[(2,2-二甲基_ι，3-二氧伍圜冰基）甲基]胺基}苯基） 128409 -59- 200836743 p奎唾琳-4(3Η)-嗣； 2- 丁基-3-{4-[(2,3-二經基丙基）胺基]苯基奎唾琳_4(3Η)_酮； Ν-[4-(2-丁基-4-酮基喹唑啉-3(4Η&gt;基）苯基]甲烷磺醯胺； Ν-[4-(2-丁基-4-酮基喹唑啉-3(4Η)-基）苯基]乙醯胺； Ν-[4-(2-丁基-4-酮基峻唾琳-3(4Η)-基）苯基]-Ν-(甲續基）甲烧 磺醯胺； 3- [4-(—氮四圜-3-基胺基）苯基]-2-丁基ρ奎唾琳-4(3Η)-酮鹽酸 鹽；Q is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or an alkyl group; R is a phenyl group, optionally substituted by one or more substituents selected from the group consisting of a group, a pyridyl group, a yl group, and a halogen group. Base, -R6 -CN, -R6 -OR5, -R6 _〇c(0)R4, -R6-0S(0)2R4, -R6-C(9)0R4, _R6_c(〇)n(r4)r5, _Rbn(( R4)r5, -R6-N(R5)C(〇)R4, -R6-N(R5)C(〇)〇R4, _R6-N(r5)c(〇)n(R4)r5, -R6- N[S(0)tR4]2 , -R6 -N(R5 )C(=NR5 )N(R4 )R5 , -R6 -N(R5 )C(=NR5 )N(R4 )CN , -R6 -N (R5)-R7 -N(R4)R5, -R6-N(R5)C[=N^0R4]-N(R4)-C(0)0R4, _r6-N=^^^ -R6-N= C(R4)R5, -R6_N(R5)-R6-〇r5 and _R6-S(〇)tN(R4)R5, wherein each p-system is independently 0, 1 or 2, and each t-system is independently 1 or 2; 128409 - 56- 200836743 Each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, _alkyl, optionally substituted aryl, optionally substituted heterocyclic, optionally substituted heterocyclic An alkyl group and optionally a substituted heteroaryl group; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclic group or an optionally substituted n-heteroaryl group; R6 is a direct bond, as appropriate a chain or branched subalkyl chain, optionally substituted straight or branched subalkenyl chain or optionally substituted linear or branched nalynyl chain; and R7 is straight or branched a secondary chain, a linear or branched sub-dense chain or a straight bond or a branched sub-fast bond. Another specific embodiment is a compound of formula (1) as set forth above in the Summary of the Invention, which is selected from the group consisting of: 2· butyl (4-methoxyphenyl) p kujunlin 4(3Η)-ketone 4-(2-butyl-4-ketoquinazolin-3(4Η)-yl)benzamide; 2-amino-2-benzoic acid 4-(2-butyl-4-ketooxazoline -3(4Η)-yl)phenyl ester; 2-[(1-methoxy-4-pentyl)amino]benzoic acid 4-(2-butyl-4-ketooxazoline-3(4Η)-yl Phenyl ester; (1Ζ)-Ν-[4-(2-butyl-4-ketooxazoline-3(4Η)-yl)phenyl]pentimine methyl ester; trifluoromethanesulfonic acid 4 -(2-butyl-4-ketoquinazolin-3(4Η)-yl)phenyl ester; 3-(4-aminophenyl)-2-butylsulfanyl-4(311)-酉; 4-(2-butyl-4-ketooxazoline-3(4Η)-yl)benzenesulfonamide; 4-(2•butyl-4-ketoquinazolin-3(4Η)-yl Methyl benzoate; 4-(2-butyl-4-ketooxazoline-3(4Η)-yl)benzoic acid; 3-(4-bromophenyl)-2-butyloxazoline-4 (3Η)-ketone; 128409 -57- 200836743 3-(3-Aminophenyl)_2-butylquinazoline·4(3Η&gt;ketone; 1·[4-(2-butylhryl quinazola) -3 - butyl-3-[4-(methylamino) 5-quinazoline-4(3Η)-one; 3-(4-aminophenyl)-2-methyloxazoline-4 (3Η&gt;ketone; 3-(3-aminophenyl)-2 -methyloxazoline-4(3Η)-one; 3-(4-aminophenyl)-2-pentyloxazoline-4 (3Η&gt;ketone; 3-(4-aminophenyl)-2 -propylquinazoline-4(3Η)-one; 2-butyl-3-[4-7-Butyl-2-ylamino)phenyl]ρ奎唾淋-4(3Η)-one; 2· Butyl-3-(4-moffin-4-ylphenyl)-Saliva-4(3H)-S; 2-butyl-3-(4-fluorophenyl)oxazoline-4 ( 3H)-keto; 3-(2-aminophenyl)-2-butyloxazoline-4(3H)-one; 1-[4-(2-butyl-4-ketooxazoline- 3(4H)·yl)phenyl]indole; 2-butyl-3-(4-chlorophenyl)quinazolin-4(3H)-one; H4-(2-butyl-4-ketoquinequine Oxazoline-3(4H&gt;yl)phenyl]_3_cyanoquinone; 3·{[4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]amino} Tetrahydropyrrole-1·carboxylic acid tert-butyl ester; 2-butyl-3-[4-(tetrahydro-p-butyr-3-ylamino)phenyl] squaring p--4 (3H)- K; 2-butyl each (4-{[2-(dimethylamino)ethyl]amino}phenyl)quinazoline-4(3H)-one; 2-butyl-3-[4- (4-methylhexachloro-p-hept-1-yl)phenyl]p-kujunlin-4(3H)-oxime; 2-butyl-3 (4-hexachloropropen-1-ylphenyl) 嗤 嗤 -4(3H)-S with; 3-(4-amino-2,5-dimethylphenyl)-2-butylquin Oxazoline-4(3H)-one; 3-(4-aminophenyl)·2_ethyl p-quinoline-4(3H)-indole; 4-(2-butyl-4-ketoquinoquine Oxazoline-3(4H)-yl)benzonitrile; 3-(4-amino-2,3,5,6-tetradecylphenyl)-2-butyloxazoline-4(3H)- Ketone; 128409 -58 - 200836743 3-(4-Amino-2,5-diphenyl)-2-butyl p-quinone-4(3H)-one; 3-(4-bromo-2 -fluorophenyl)-2-butyl p-quineline-4(3H)-one; 3-[4-(aminomethyl)phenyl]-2-butylquinazoline-4(3H)- Ketone; [4_(2_butyl_4. ketoquinazoline-3(4H)-yl)] benzyl carbamic acid tert-butyl ester; 3-(4-Molyl-2-chlorophenyl) -2-butyljunsin-4,3H-one; 3-[4-bromo-2-(trifluoromethyl)phenyl]-2-butyloxazoline-4(3H)-one; 3-(4bromo-2,6-difluorophenyl)-2-butylp-quineline-4(3H)-one; 3-(4-diyl-2-methylphenyl)- 2_butyl sulphate-4(311)-ketone; (_ 3-(4-Molyl-2,6-dimethylphenyl)-2-butyl p-quinone _4(3H)-S Same as; 2-butyl-3-(2-chloro-4-morpholine-4-ylphenyl) quinazoline-4 (3H&gt;ketone; 2·butyl _3-[4-Morfolin-4-yl-2-(trifluoromethyl)phenyl]4oxazoline-4(3H)-one; 2-butyl-3-(2,6-difluoro- 4-morpholine-4-ylphenyl)oxazoline-4(3H)-one; 2-butyl-3-(2-methyl-4-norfos-4-ylphenyl)carbazole Lin-4(3H)-keto; 2-butyl-3-(2,6-dimethylnorbornolin-4-ylphenyl)oxazoline·4(3Η)-ϊ同; 2-but Benzyl-3-(2-ranyl-4-whufolin-4-ylphenyl) τί奎u sitting on Ρ林_4(3Η)_阙; 2-butyl-3-(4-hexahydro-say bite -1-ylphenyl&gt; quinazoline _4(3Η)-one; i 2_butyl-3·[4_(hexahydrop-biti-3-ylamino)phenyl p-quineline_4 (3H)-keto; 3-[4-Amino-3-(trifluoromethyl)phenyl]-2-butylp-quinazoline-4(3H)-one; 3-[4-Amino- 2-(trifluoromethyl)phenyl]-2-butylcarbazole p-lin-4(3H)·one; 2-butyl-3-{4-[(2-hydroxy-3-phenoxypropane Amino]phenyl}p-quinazoline·4(3Η)_one; 2-butyl-3-{4-[2-(phenoxyindenyl))folin _4_yl]phenyl }ρ奎唑4 4(3Η)-ketone; 2-butyl-3-(4-{[(2,2-dimethyl-,3,2-dioxo)-yl]amino]amino} Phenyl) 128409 -59- 200836743 p-quinine--4(3Η)-嗣; 2-butyl-3-{4-[(2,3-dipropylpropyl)amino] Phenylquinidine _4(3Η)-one; Ν-[4-(2-butyl-4-ketoquinazolin-3(4Η&gt;yl)phenyl]methanesulfonamide; Ν-[4 -(2-butyl-4-ketoquinazolin-3(4Η)-yl)phenyl]acetamide; Ν-[4-(2-butyl-4-keto) 4-Η)-yl)phenyl]-indole-(methyl thiol)methyl sulfonamide; 3-[4-(-azatetraindole-3-ylamino)phenyl]-2-butyl ρ 唾Lin-4(3Η)-ketohydrochloride;

/ V 2-丁基-3-{4-[(7a，S)-3-酮基四氫-1Η-吡咯并[l，2-c]咪唑-2(3Η)-基] 苯基}喳唑啉-4(3Η&gt;酮； 2·丁基-3-{4-[(3R)-六氫ρ比唆-3-基胺基]苯基奎嗅ρ林-4(3H)-i同鹽 酸鹽； 2- 丁基-3-[4-(四氫吡咯-3-基氧基）苯基]喳唑啉-4(3H)_酮二鹽酸 鹽； 3- 丁基-2-[4-(四氫吡咯-3-基胺基）苯基]喹唑啉-4(3Η)-ί同鹽酸 鹽， (R) -2-丁基-3-(4-(四氫吡咯-3-基胺基）苯基）喹唑啉-4(3H)-酮；及 (S) -2-丁基-3-(4-(四氫吡咯-3-基胺基）苯基）喹唑啉-4(3H)-酮鹽酸 鹽。 另一項具體實施例為如上文在發明内容中所提出之式① 化合物，其係選自包括： 2-丁基-3-(4-經苯基）峻嗤淋_4(311)-酮； 2-丁基-3-{4-[(二苯亞甲基）胺基]苯基}喹唑啉_4(3H)_酮； [4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]胺基甲酸第三-丁酯； 128409 •60- 200836743 [4-(4-酮基-2-丙基p奎唾琳-3(4H)-基）苯基]胺基曱酸第三-丁酯； [4-(2-乙基-4-酮基峻唑琳-3(4H)-基）苯基]胺基甲酸第三_丁酯； [4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]甲基胺基甲酸第三-丁 酯； [2-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]胺基甲酸第三-丁酯； [4-(2-丁基-4-酮基喳唑啉-3(4H)-基）-3-(三氟甲基）苯基]胺基甲 酸第三-丁酯； [(第三-丁氧魏基）胺基]{[4-(2-丁基-4-酮基峻唾琳-3(4H)-基）苯 基]胺基}亞甲基]胺基甲酸第三-丁酯； [4-(2-丁基-4-酮基喹唑啉-3(4H)-基）爷基]胺基甲酸第三-丁酯； [4_(2-丁基-4-酮基喳唑啉-3(4H)-基）-2-(三氟曱基）苯基]胺基甲 酸第三-丁酯； 4-[4-(2-丁基-4-酮基峻唑琳-3(4H&gt;基）苯基]六氫吡畊-μ羧酸第 三-丁酯； 3-{[4_(2-丁基·4-酮基喹唑啉-3(4H)-基）苯基]胺基}六氫吡啶 羧酸第三-丁酯； 3-{[4-(2-丁基-4·酮基喹唑啉-3(4Η)-基）苯基]胺基} 一氮四圜小 羧酸第三-丁酯； (3R)-3-{[4-(2-丁基_4_酮基喹唑啉-3(4Η)-基）苯基]胺基}六氫吡咬 -1-羧酸第三-丁酯； 3-[4-(2-丁基-4-酮基峻♦琳_3(4Η)_基）苯氧基]四氫ρ比略小魏酸 第三-丁酉旨； 2- (4-溴苯基）_3_丁基喳唑啉-4(3Η)-酮； 3- (4-(3-丁基-4-酮基-3,4-二氫喹唑啉-2-基）苯基胺基）四氫吡略 128409 -61 - 200836743 -1-羧酸第三-丁酯； (R) -3-(4-(2-丁基-4-酮基4嗤啉_3(4H)_基）苯基胺基）四氫吡咯小 羧酸第三-丁酯；及 (S) _3-(4-(2-丁基-4,基峻唾琳-3(4H)_基）苯基胺基）四氫吡咯小 魏酸第三-丁醋。 另一項具體實施例為如上文所示之式（〗）化合物，其中： η為1 ;/V 2-butyl-3-{4-[(7a,S)-3-ketotetrahydro-1Η-pyrrolo[l,2-c]imidazole-2(3Η)-yl]phenyl}喳Oxazoline-4 (3Η&gt;ketone; 2·butyl-3-{4-[(3R)-hexahydroρ than indol-3-ylamino]phenyl quinolone phlin-4(3H)-i Hydrochloride; 2-butyl-3-[4-(tetrahydropyrrol-3-yloxy)phenyl]oxazoline-4(3H)-one dihydrochloride; 3-butyl-2- [4-(tetrahydropyrrol-3-ylamino)phenyl]quinazoline-4(3Η)-ί-HCl, (R)-2-butyl-3-(4-(tetrahydropyrrole) -3-ylamino)phenyl)quinazolin-4(3H)-one; and (S)-2-butyl-3-(4-(tetrahydropyrrol-3-ylamino)phenyl) Quinazoline-4(3H)-one hydrochloride. Another specific embodiment is a compound of formula 1 as set forth above in the Summary of the Invention, which is selected from the group consisting of: 2-butyl-3-(4- Benzyl) 嗤4(311)-ketone; 2-butyl-3-{4-[(diphenylmethylene)amino]phenyl}quinazoline-4(3H)-one; [4-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]carbamic acid tert-butyl ester; 128409 • 60-200836743 [4-(4-keto- 2-propyl p-quineline-3(4H)-yl)phenyl]amino decanoic acid tert-butyl ester; [4-(2-ethyl-4-keto-trendazole-3) - Phenyl]aminocarboxylic acid tert-butyl ester; [4-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]methylcarbamic acid tert-butyl ester [2-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]carbamic acid tert-butyl ester; [4-(2-butyl-4-keto) Oxazoline-3(4H)-yl)-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester; [(t-butoxy-wei)amino]{[4-( 2-butyl-4-keto-threatelin-3(4H)-yl)phenyl]amino}methylene]carbamic acid tert-butyl ester; [4-(2-butyl-4- Ketoquinazoline-3(4H)-yl)-ylaminocarbamic acid tert-butyl ester; [4_(2-butyl-4-ketooxazoline-3(4H)-yl)-2 -(Trifluoromethyl)phenyl]carbamic acid tert-butyl ester; 4-[4-(2-butyl-4-keto-trendazole-3(4H&gt;yl)phenyl]hexahydropyridyl Till-μcarboxylic acid third-butyl ester; 3-{[4_(2-butyl·4-ketoquinazolin-3(4H)-yl)phenyl]amino}hexahydropyridinecarboxylic acid third - butyl ester; 3-{[4-(2-butyl-4. ketoquinazolin-3(4Η)-yl)phenyl]amino}-nitro-tetrazepine carboxylic acid tert-butyl ester; (3R)-3-{[4-(2-butyl-4-ketoquinazolin-3(4Η)-yl)phenyl]amino}hexahydropyridin-1-carboxylic acid third- Ester; 3-[4-(2-butyl-4-keto) phenanthrene _3(4Η)-yl)phenoxy]tetrahydro ρ is slightly smaller than the third acid - butyl hydrazine; 2- (4 -bromophenyl)_3_butyloxazoline-4(3Η)-one; 3-(4-(3-butyl-4-keto-3,4-dihydroquinazolin-2-yl) Phenylamino)tetrahydropyrrol 128409 -61 - 200836743 1-carboxylic acid tert-butyl ester; (R)-3-(4-(2-butyl-4-keto-4-carboline-3) 4H)-yl)phenylamino)tetrahydropyrrole small carboxylic acid tert-butyl ester; and (S) _3-(4-(2-butyl-4, thiophenanthene-3(4H)-yl) ) Phenylamino) tetrahydropyrrole weiwei acid third-butyl vinegar. Another specific embodiment is a compound of formula () as shown above, wherein: η is 1;

Q 為稠合苯基；Q is a fused phenyl group;

Ri為氯； R為氫或烧基； R3為萘基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、_基、_烷基、_烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、_R6_CN、_R6_N〇2、_r6_qr5、 -R6-0C(0)R4、-R6-〇S(〇)2R4、-R6((〇)R4、_r6_c(〇)〇r4、 -R6 -C(0)N(R4 )R5、-r6 -N(R4 )R5、r6 _n(r5 )c(〇)r4、 128409 -62- 200836743 -R6 -N(R5 )C(0)0R4、-R6 -N(R5 )C(0)N(R4 )R5、-R6 -N(R5 )S(0)t R4 ^ -R6-N[S(0)tR4]2 &gt; -R6-N(R5)C(=NR5)N(R4)R5 ^ -R6-N(R5&gt; C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 ^ -R6-N=C(R4)R5 ^ -R6-N=C(R4)R5 、-R6_N(R5)-R6-〇R5 、-R6-S(0)PR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇, ：i或2，且各t係獨 立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、函烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之弋（I) 化合物，其係為3_(5_胺基茬小基）-2-丁基喹唑琳，犯),。 另一項具體實施例為如上文所示之式①化合物，其中： η為1 ; 128409 -63- 200836743 Q. 為稠合本基， R1為氫； R2為氫或烧基； R3為雜芳基，視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、鹵基、鹵烷基、鹵烯基、齒 炔基、視情況經取代之環烷基、視情況經取代之環炫 基烧基、視況經取代之壞烧基稀基、視情況經取 代之丨衣烧基快基、視情況經取代之芳基、視情況經取 代之芳烷基、視情況經取代之芳烯基、視情況經取代 之芳炔基、視情況經取代之雜環基、視情況經取代之 雜環基烷基、視情況經取代之雜環基烯基、視情況經 取代之雜環基炔基、視情況經取代之雜芳基、視情況 經取代之雜芳烷基、視情況經取代之雜芳基烯基、視 情況經取代之雜芳基炔基、_R6_CN、-R6-N〇2、_r6_〇r5、 -R6-0S(0)2R4、-R6_〇C(〇)r4、-R6-C(〇)R4、r6-C(〇)〇r4、 -R6-C(0)N(R4)R5、-R6-N(R4)R5 &gt; -R6-N(R5)C(0)R4 ^ -R6-N(R5 )C(0)0R4 . -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5 )S(0)t R4 -R6-N[S(0)tR4]2 &gt; -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5)-C(=NR5 )N(R4 )CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4&gt;C(0)0R4 ^ •R6-N(R5)-R7-N(R4)R5、_R6-N=C(OR4)R5、-R6_n=C(R4)R5、 -R6-N(R5)_R6-〇R5、-R6_s(〇)pR4 及 r6 _s(⑺tN(R4)R5，其中各 P係獨立為0, 1或2，且各t係獨立為1或2 ; 各R&gt;R5係、獨立選自包括氫、縣、烯基、快基、鹵燒基、 128409 -64 - 200836743 經烧基、燒氧烧基、視情況經取代之環燒基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N·雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式① 化合物，其係選自包括： 5-(2-丁基-4-酮基峻°坐琳-3(4H)-基）-2,3-二氫-1H-H丨嗓-1魏酸第 三-丁酯； 5-(2-丁基-4-酮基峻°坐琳-3(4H)-基）_1Η-Θ丨嗓-1-魏酸第三-丁酉旨； 2-丁基-3-(2,3-二氫-1Η-4卜朵-5-基）ρ奎唾琳 _4(3Η)_嗣； 2-丁基-3-(1Η-啕哚-5-基）喹唑啉-4(3Η)-酮； 2·丁基-3-(2-S同基-2,3-二氫-1，3-苯并3 β坐-5-基）ρ奎唾琳-4(3Η)-酮； 5-(2-丁基-4-酮基喳唑啉-3(4Η)-基）-1Η-啕唑-1-羧酸第三-丁酯； 2-丁基-3-(2-硫酮基-2,3-二氫-1Η-苯并咪唾-5-基 &gt;奎峻琳-4(3Η)、 酮； 2-丁基卜坐-5-基 &gt;奎峻淋-4(3Η)-_ ; 128409 • 65- 200836743 3-(1Η-苯并三唑-5-基）-2-丁基喹唑啉-4(3H)-酮； 3·(6-胺基吡啶各基）·2-丁基哇唑啉_4(3H)-酮； 2- 丁基-3-吡啶-4-基喳唑啉-4(3H)-酮； 3- (1，3-苯并二氧伍圜烯基）丁基喹唑啉-4(3H)_酮； 2-丁基_3-(6-甲氧基吡啶-3-基）喹唑啉-4(3H)-酮； 5-(2•丁基-4-酮基喹唑啉_3(4H)-基）-2,3-二氫-1H-吲哚-1-羧酸第 三_丁酯； 2·丁基-3-(6-酮基-5,6-二氫吡啶-3-基）喳唑啉-4(3H&gt;酮；及 / 2-丁基-3-(1-羥基-1,2-二氫吡啶-4-基）喳唑啉-4(3H)-酮。 另一項具體實施例為如上文在發明内容中所提出之式⑴ 化合物，其係選自包括： 2-丁基-3-(2-硫基-1H-苯并咪唑_5_基 &gt;奎唑啉_4(3H)-S同； [5-(2-丁基-4-酮基p奎唾琳-3(4H)-基）吡唆-2-基]胺基甲酸第三-丁 酯；及 2-丁基-3-(1-氧化吡啶-4_基）p奎唑啉-4(3H)-酮。 另一項具體實施例為如上文所示之式（I)化合物，其中： i , η為1 ; Q、. 為稠合笨基； R1為氫； R2為氫或烷基； R3為雜環基，視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、鹵基、鹵烷基、鹵烯基、南 炔基、視情況經取代之環烧基、視情況經取代之譬广 128409 -66· 200836743 基烷基、視情況經取代之環烷基烯基、視情況經取代 之環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、-R6_N〇2、_r6_〇r5、 -R6-0S(0)2R4 &gt; -R6-〇C(0)R4 &gt; -R6-C(0)R4 &gt; .R6-C(0)0R4 &gt; -C(〇)N(R4 )R5、_R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)0R4 &gt; -R6-N(R5)C(0)N(R4)R5 . -R6-N(R5)S(0)tR4 、-R6 -N[S(0)t R4 ]2 、-R6 -N(R5 )C(=NR5 )N(R4 )R5 、 -R6-N(R5)C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)〇R4]-N(R4&gt; C(0)〇R4、-R6 -N(R5 )-R7 -N(R4 )R5 -R6 -N=C(OR4 )R5 -R6 -NC(R4 )R5 、-R6 -N(R5 )-R6 -〇R5 、_R6 -S(〇)p r4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇, }或2，且各丨係獨 立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 128409 -67- 200836743 N-雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次快基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式① 化合物，其係選自包括： 2- 丁基各[1-(2-經基-3-苯氧基丙基）六氫咕唆-4-基]峻唾p林 -4(3H)_ 酮； 3- {1·[3-(爷氧基）_2_經丙基]六氫p比。定冰基}-2_丁基ρ奎嗤4木-4(3H)_ 0¾ ； 經基-3-苯氧基丙基）六氫p比α定·4_基]峻唾4 _4(3H)_酮； 4- (2-丁基斗酮基喹唑啉_3(4H)_基）六氫吡啶小羧酸第三-丁 酯；及 2-丁基-3_六氫吡啶斗基喳唑啉-4(3H)_酮。 V - 另一項具體實施例為如上文所示之式（I)化合物，其中： η為1 ; 0.. 為稠合苯基； R1為氫； R為氣或烧基； R3為環烷基，視情況被一或多個取代基取代，取代基選自 包括烧基、烯基、炔基、鹵基、i烷基、鹵烯基、_ 128409 -68- 200836743 炔基、視情況經取代之環烷基、視情況經取代之環烷 基烧基、視情況經取代之環烧基烯基、視情況經取代 之環烧基快基、視情況經取代之芳基、視情況經取代 之芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烷基、視情況經取代之雜環基烯基、視情況經取 代之雜壞基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、nCN、nN〇2、、 -R6-0C(0)R4、-RLOS(〇)2R4、_r6 _c(〇)r4、_r6 _c(〇)〇r4、 -R6 -C(0)N(R4 )R5、_R6 _n(r4 )r5、_r6 _n(r5 )c(〇)r4、 -R6-N(R5 )C(0)〇R4 . -R6-N(R5 )C(0)N(R4 )R5 ^ -R6-N(R5 )S(0)t R4 Λ 'R6-N[S(〇)tR4]2 . -R6-N(R5)C(=NR5)N(R4)R5 . -R6-N(R5&gt; C(-NR )N(R4)CN、-R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4、 -R -N(R5)-R7-N(R4)R5、-R6 养c(OR4)R5、_R6-N=C(R4)R5、 -R6-N(R5)-R6-OR5、-R6-S(〇)pRns(〇)tN(R4)R5 4*&amp; P係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、齒烷基' I工烧基烧氧烧基、視情況經取代之環烧基、視猜況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R與R5和彼兩者所連接之氮一起，形成視情況經取代之 128409 -69- 200836743 N雜環基或視情況經取代之N—雜芳基； 各R為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鍵、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 、、二取代之直鏈或分枝狀次快基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式⑺ 化合物，其係選自包括： (4 基環己基）_2_丁基峻唾琳酮；與 [4-(2_丁基-4-酮基喳唑啉-3(411&gt;基）環己基]胺基甲酸第三·丁Ri is chlorine; R is hydrogen or alkyl; R3 is naphthyl, optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, yl, _alkyl, ene Alkyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally Substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl Alkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted Arylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, _R6_N〇2, _r6_qr5, -R6-0C(0)R4, -R6-〇S(〇)2R4, -R6((〇)R4 , _r6_c(〇)〇r4, -R6 -C(0)N(R4)R5, -r6 -N(R4)R5, r6 _n(r5)c(〇)r4, 128409 -62- 200836743 -R6 -N (R5)C(0)0R4, -R6 -N(R5)C(0)N(R4)R5, -R6 -N(R5)S(0 )t R4 ^ -R6-N[S(0)tR4]2 &gt; -R6-N(R5)C(=NR5)N(R4)R5 ^ -R6-N(R5&gt; C(=NR5)N( R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4^-R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 ^ -R6-N=C(R4)R5 ^ -R6-N=C(R4)R5 , -R6_N(R5)-R6-〇R5 , -R6-S(0 PR4 and -R6-S(0)tN(R4)R5, wherein each p is independently 〇, :i or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, Alkyl, alkenyl, alkynyl, alkenyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, Optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 Together with the nitrogen to which R5 and the two are attached, form an optionally substituted N-heterocyclic group or an optionally substituted group heteroaryl; each R6 is a direct bond, optionally substituted straight chain or sub. Branched subalkyl chain, optionally substituted straight or branched subalkenyl chain or optionally substituted straight chain or Dendritic times alkynyl chain; and R7 is a straight-chain or branched alkylidene chain, a straight or branched alkenylene chain or secondary linear or branched alkynyl chain views. Another specific embodiment is the ruthenium (I) compound as set forth above in the Summary of the Invention which is 3-(5-aminoindolyl)-2-butylquinazoline, s. Another specific embodiment is a compound of formula 1 as shown above, wherein: η is 1; 128409 - 63- 200836743 Q. is a fused base, R1 is hydrogen; R2 is hydrogen or alkyl; R3 is heteroaryl And optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, alkynyl, optionally substituted cycloalkyl a cyclohexyl group which may be substituted as appropriate, a dilute base which is substituted as appropriate, an optionally substituted aryl group, an optionally substituted aryl group, optionally substituted aralkyl Alkenyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl , optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryl Alkynyl, _R6_CN, -R6-N〇2, _r6_〇r5, -R6-0S(0)2R4, -R6_〇C(〇)r4, -R6-C(〇)R4, r6-C(〇 )〇r4, -R6 -C(0)N(R4)R5, -R6-N(R4)R5 &gt; -R6-N(R5)C(0)R4^-R6-N(R5)C(0)0R4 . -R6- N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)t R4 -R6-N[S(0)tR4]2 &gt; -R6-N(R5)C (=NR5 )N(R4 )R5 - -R6-N(R5)-C(=NR5 )N(R4 )CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4&gt; C(0)0R4 ^ •R6-N(R5)-R7-N(R4)R5, _R6-N=C(OR4)R5, -R6_n=C(R4)R5, -R6-N(R5)_R6- 〇R5, -R6_s(〇)pR4 and r6_s((7)tN(R4)R5, wherein each P is independently 0, 1 or 2, and each t is independently 1 or 2; each R&gt;R5 is independently selected from Including hydrogen, county, alkenyl, fast-group, halogenated group, 128409-64 - 200836743, alkyl group, calcined base, optionally substituted cycloalkyl group, optionally substituted cycloalkylalkyl group, Substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted a heteroarylalkyl group; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N. heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct bond, optionally Replaced straight chain or a branched alkylene chain, optionally substituted straight or branched subalkenyl chain or optionally substituted linear or branched nalynyl chain; and R7 is straight or branched An alkyl chain, a linear or branched subalkenyl chain or a linear or branched subalkynyl chain. Another specific embodiment is a compound of formula 1 as set forth above in the Summary of the Invention, which is selected from the group consisting of: 5-(2-butyl-4-keto-thenyl-3,4H)-yl) -2,3-dihydro-1H-H丨嗓-1 -tricarboxylic acid tert-butyl ester; 5-(2-butyl-4-keto-threateine-salt-3(4H)-yl)_1Η-Θ丨嗓-1-Weinic acid Third-Dingzhi; 2-butyl-3-(2,3-dihydro-1Η-4bido-5-yl)ρ奎唾琳_4(3Η)_嗣; 2-butyl-3-(1Η-indol-5-yl)quinazolin-4(3Η)-one; 2·butyl-3-(2-S-iso-2,3-dihydro-1 , 3-benzo-3β--5-yl) ρ 奎 唾 -4 -4(3Η)-one; 5-(2-butyl-4-ketooxazoline-3(4Η)-yl)-1Η - oxazole-1-carboxylic acid tert-butyl ester; 2-butyl-3-(2-thioketo-2,3-dihydro-1 fluorene-benzopyran-5-yl) 奎奎琳-4(3Η), ketone; 2-butyl sulphate-5-yl group&gt;奎峻淋-4(3Η)-_; 128409 • 65- 200836743 3-(1Η-benzotriazol-5-yl) -2-butylquinazoline-4(3H)-one; 3·(6-aminopyridine each)·2-butyl oxazoline-4(3H)-one; 2-butyl-3- Pyridin-4-yloxazoline-4(3H)-one; 3-(1,3-benzodioxolanyl)butylquinazoline-4(3H)-one; 2-butyl_ 3-(6-methoxypyridine -3-yl)quinazoline-4(3H)-one; 5-(2,butyl-4-ketoquinazoline-3(4H)-yl)-2,3-dihydro-1H-indole哚-1-carboxylic acid third-butyl ester; 2·butyl-3-(6-keto-5,6-dihydropyridin-3-yl)oxazoline-4 (3H&gt;ketone; and / 2 -butyl-3-(1-hydroxy-1,2-dihydropyridin-4-yl)oxazoline-4(3H)-one. Another specific embodiment is as set forth above in the Summary of the Invention a compound of the formula (1), which is selected from the group consisting of: 2-butyl-3-(2-thio-1H-benzimidazole-5-yl) quinazoline-4(3H)-S; [5-( 2-butyl-4-keto-p-quineline-3(4H)-yl)pyridin-2-yl]carbamic acid tert-butyl ester; and 2-butyl-3-(1-oxidized pyridine) -4_yl)p-quinazoline-4(3H)-one. Another specific embodiment is a compound of formula (I) as shown above, wherein: i, η is 1; Q,. is fused R1 is hydrogen; R2 is hydrogen or alkyl; R3 is heterocyclic, optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, haloalkyl , haloalkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted 譬 128 128409 -66· 200836743 alkyl, depending on the situation Substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted Aryl alkynyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally Substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, -R6_N〇2, _r6_〇r5, -R6-0S(0)2R4 &gt; -R6-〇C(0)R4 &gt; -R6-C(0)R4 &gt; .R6-C(0)0R4 &gt; -C(〇)N(R4 ) R5, _R6 - N(R4)R5, -R6 - N(R5)C(0)R4, -R6-N(R5)C(0)0R4 &gt; -R6-N(R5)C(0)N( R4)R5 . -R6-N(R5)S(0)tR4 , -R6 -N[S(0)t R4 ]2 , -R6 -N(R5 )C(=NR5 )N(R4 )R5 , R6-N(R5)C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)〇R4]-N(R4&gt; C(0)〇R4, -R6 -N (R5)-R7 -N(R4)R5 -R6 -N=C(OR4)R5 -R6 -NC(R4)R5, -R6 -N(R5)-R6 -〇R5, _R6 -S(〇)p R4 and -R6-S(0)tN(R4)R5, wherein each p-system is independent , } or 2, and each lanthanide is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally Substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted a cycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached, form an optionally substituted 128409-67-200836743 N a heterocyclic group or an optionally substituted N-heteroaryl group; each R6 is a direct-bonded, optionally substituted straight or branched alkylene chain, optionally substituted straight or branched a secondary alkenyl chain or an optionally substituted straight or branched sub-fast chain; and R7 is a linear or branched subalkyl chain, a straight or branched subalkenyl chain or a straight chain or a sub. Dendritic acetylene chain. Another specific embodiment is a compound of formula 1 as set forth above in the Summary of the Invention, which is selected from the group consisting of: 2-butyl[1-(2-amino-3-phenoxypropyl)hexahydro咕唆-4-yl] 唾 p plin-4(3H) ketone; 3-{1·[3-(yloxy)_2_propyl)hexahydrop ratio.定冰基}-2_butyl ρ 奎嗤4木-4(3H)_ 03⁄4 ; benzyl-3-phenoxypropyl)hexahydrop ratio α · 4 _ base] 唾 4 4 _4 (3H a ketone; 4-(2-butylbuxenylquinazoline-3(4H)-yl)hexahydropyridine small carboxylic acid tert-butyl ester; and 2-butyl-3_hexahydropyridine Oxazoline-4(3H)-one. V - another specific embodiment is a compound of formula (I) as shown above, wherein: η is 1; 0.. is a fused phenyl group; R1 is hydrogen; R is a gas or a burnt group; R3 is a cycloalkane And optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, i-alkyl, haloalkenyl, _128409-68-200836743 alkynyl, optionally Substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylenyl, optionally substituted cycloalkyl radical, optionally substituted aryl, optionally Substituted arylalkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted Cycloalkenyl, optionally substituted heterocyclynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted Heteroarylalkynyl, nCN, nN〇2, -R6-0C(0)R4, -RLOS(〇)2R4, _r6 _c(〇)r4, _r6 _c(〇)〇r4, -R6 -C( 0) N(R4 )R 5, _R6 _n(r4)r5, _r6 _n(r5)c(〇)r4, -R6-N(R5)C(0)〇R4 . -R6-N(R5 )C(0)N(R4 )R5 ^ -R6-N(R5 )S(0)t R4 Λ 'R6-N[S(〇)tR4]2 . -R6-N(R5)C(=NR5)N(R4)R5 . -R6-N (R5&gt; C(-NR )N(R4)CN, -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4, -R -N(R5)- R7-N(R4)R5, -R6 raise c(OR4)R5, _R6-N=C(R4)R5, -R6-N(R5)-R6-OR5, -R6-S(〇)pRns(〇) tN(R4)R5 4*&amp; P is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and dentate An alkyl 'I-alkyl oxyalkyl group, optionally substituted cycloalkyl group, optionally substituted cycloalkylalkyl group, optionally substituted aryl group, optionally substituted aralkyl group, Optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R and R5 and both Together with nitrogen, form an optionally substituted 128409-69-200836743 N-heterocyclyl or optionally substituted N-heteroaryl; each R is a direct-bonded, optionally substituted linear or branched hypoalkane Base key a substituted linear or branched sub-alkenyl chain or, as appropriate, a disubstituted linear or branched sub-fast chain; and R7 is a linear or branched alkylene chain, linear or A branched secondary alkenyl chain or a linear or branched subalkynyl chain. Another specific embodiment is a compound of formula (7) as set forth above in the Summary of the Invention, which is selected from the group consisting of: (4-cyclohexyl)_2-butyl-threlinone; and [4-(2-butyl-4) -ketooxazoline-3(411&gt;yl)cyclohexyl]aminocarbamic acid third·ding

Sg ° 另一項具體實施例為如上文所示之式①化合物，其中 η 為 1 ; '、 為稠合苯基；Another embodiment of the invention is a compound of formula 1 as shown above, wherein η is 1; ', is a fused phenyl group;

Rl為氫；Rl is hydrogen;

R2為氫或烷基； 基院基、視情況經取代之環院基稀基、視情況經取代 之環烧基块基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 r3為芳院基’視情況被-或多個取代基取代，取代基選自 匕括院基、烯基、炔基、由基、函院基、幽烯基、函 块基、視情況經取代之環燒基、視情況經取代之環烧 128409 -70- 200836743 環基燒基、視情況經取代之雜環基烯基、視情況經取 代之雜裱基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基块基、-R6 、-R6 _N〇2、_R6 _〇ρ5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 λ -R6-C(〇)R4 ^ -R6-C(0)0R4 &gt; -R6 -C(0)N(R4 )R5 -R6 _N(R4 )R5、-R6 -N(R5 )C(0)R4 -R6-N(R5 )C(0)〇R4 &gt; -R6-N(R5 )C(0)N(R4 )R5 &gt; -R6-N(R5 )S(0)tR4 -R6-N[S(0)tR4]2 - -R6-N(R5 )C(=NR5 )N(R4 )R5 &gt; -R6-N(R5)-C(-NR5 )N(R4 )CN &gt; -r6-N(R5)C[=NC(0)0R4].N(R4)-C(0)0R4 &gt; -R6-N(R5)-R7_N(R4)R5、妒养c(〇R4)R5、_R6 -N=C(R4)R5、 -R6 -N(R5 )-R6 -OR5、-R6 -S(〇)p R4 及-r6 -S(〇)tN(R4 )r5，其中各 p係獨立為0, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烧基烧基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與V和彼兩者所連接之氮—起，形成視情況經取代之 N-雜環基或視情況經取代之]^雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次燒基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 128409 -71 - 200836743 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式①化合物，其中： η為1 ;R 2 is hydrogen or an alkyl group; a base group, optionally substituted ring-based base, optionally substituted cycloalkyl group, optionally substituted aryl, optionally substituted aralkyl, An optionally substituted aralkenyl group, optionally substituted aralkynyl group, optionally substituted heterocyclic group, optionally substituted hetero-r3, is substituted by the aryl group, as the case may be, or substituted by a plurality of substituents, The substituent is selected from the group consisting of an anthracene group, an alkenyl group, an alkynyl group, a decyl group, a halo group, a decyl group, a block group, a cycloalkyl group which may be optionally substituted, and a ring-fired 128409-70-substituted as appropriate. 200836743 Cycloalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterofluorenyl, heteroaryl optionally substituted, optionally substituted heteroaryl, optionally as appropriate Substituted heteroarylalkenyl, optionally substituted heteroaryl block, -R6, -R6 _N〇2, _R6 _〇ρ5, -R6-0C(0)R4 &gt; -R6-0S(0) 2R4 λ -R6-C(〇)R4 ^ -R6-C(0)0R4 &gt; -R6 -C(0)N(R4 )R5 -R6 _N(R4 )R5, -R6 -N(R5 )C( 0) R4 - R6-N(R5)C(0) 〇 R4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR 4 -R6-N[S(0)tR4]2 - -R6-N(R5)C(=NR5 )N(R4 )R5 &gt; -R6-N(R5)-C(-NR5 )N(R4 ) CN &gt; -r6-N(R5)C[=NC(0)0R4].N(R4)-C(0)0R4 &gt; -R6-N(R5)-R7_N(R4)R5, support c ( 〇R4)R5, _R6 -N=C(R4)R5, -R6 -N(R5)-R6-OR5, -R6-S(〇)p R4 and -r6 -S(〇)tN(R4)r5, Wherein each p is independently 0, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, Alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic , optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 and V and the nitrogen to which they are attached, form, as appropriate Substituted N-heterocyclyl or optionally substituted]heteroaryl; each R6 is a direct-bonded, optionally substituted straight or branched sub-alkyl chain, optionally substituted straight chain or Branched subalkenyl chain or optionally substituted linear or branched decynyl group ; And R7 is a straight-chain or branched alkylidene chain, a straight or branched alkenylene chain or a straight times 128 409 -71--200836743 Ci-chain or branched alkynyl chain. Another specific embodiment is a compound of formula 1 as shown above, wherein: η is 1;

Q 為稠合苯基； w為氫； 為氫或烧基； , R3為苄基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、基、_烷基、_烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烧基、視情況經取代之環烷基烯基、視情況經取代之 %院基快基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 、 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、-R6-CN、-R6-N02、-R6_〇R5、 -R6-0C(0)R4、-R6-0S(0)2R4、-R6-C(0)R4、-R6-C(0)0R4、 -R6-C(0)N(R4)R5 、_R6-N(R4)R5 、_R6-N(R5 )C(0)R4、 -H6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)S(0)tR4 、-R6 -N[S(0)t R4 ]2 、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 、 -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)OR4]-N(R4)-C(〇)〇r4、-r6_n(r5)-r7.n(r4)r5、-R6-N=C(OR4)R5、 !284〇9 -72- 200836743 及 獨 R6-N=C(R4)R5 . -R6-N(R5&gt;R6.〇r5 ^ _R6s(〇)pR4 -R6 -S(〇)t N(R4 )R5，其中各P係獨立為CU或2，且各t係 立為1或2 ; 、 各咖係獨立選自包括氫、烧基、稀基、炔基、齒燒基、 搜烧基、烧氧烧基、視情況經取代之環烧基、視情況 銓取代之裱烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； / 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之泎雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷美 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 i R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式⑴ 化合物，其係選自包括： 3-(4-胺基苄基丁基喹唑啉_4(3H)·酮；與 2_丁基_3_(4-硝基芊基）喹唑啉-4(3H)-酮。 另一項具體實施例為如上文所示之式（I)化合物，其中： η為1 ;Q is a fused phenyl group; w is hydrogen; is hydrogen or alkyl; R3 is benzyl, optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, phenyl, —alkyl, —alkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted Radical, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally Substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted, heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl , optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6_〇R5, -R6-0C(0)R4, -R6 -0S(0)2R4, -R6-C(0)R4, -R6-C(0)0R4, -R6-C(0)N(R4)R5, _R6-N(R4)R5, _R6-N( R5)C(0)R4, -H6-N(R5)C(0)0R4, -R6-N(R5)C(0)N(R4)R5, -R6-N(R5)S(0)tR4 , -R6 -N[S(0)t R4 ]2 , -R6 -N(R5 )C(=NR5 )N(R4 )R5 , -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[ =NC(0)OR4]-N(R4)-C(〇)〇r4, -r6_n(r5)-r7.n(r4)r5, -R6-N=C(OR4)R5, !284〇9 - 72-200836743 and R6-N=C(R4)R5 . -R6-N(R5&gt;R6.〇r5 ^ _R6s(〇)pR4 -R6 -S(〇)t N(R4 )R5, wherein each P system Independently CU or 2, and each t system is set to 1 or 2; each coffee system is independently selected from the group consisting of hydrogen, alkyl, dilute, alkynyl, dentate, search base, burned oxygen base, as appropriate Substituted cycloalkyl, optionally substituted decylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic, optionally substituted a cycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; / or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclyl Or a substituted heteroaryl group as appropriate; each R6 is a direct-bonded, optionally substituted linear or branched sub-alkane chain, optionally substituted linear or branched sub-alkenyl chain or Straight or branched as appropriate Ci alkynyl chain; and i R7 is a straight-chain or branched alkylidene chain, a straight or branched alkenylene chain or secondary linear or branched alkynyl chain views. Another specific embodiment is a compound of formula (1) as set forth above in the Summary of the Invention, which is selected from the group consisting of: 3-(4-aminobenzylbutylquinazoline-4(3H).one; - Butyl_3_(4-nitroindenyl)quinazolin-4(3H)-one. Another specific embodiment is a compound of formula (I) as shown above, wherein: η is 1;

Q 〇為稠合苯基； 128409 -73 - 200836743 R1為氫； R2為氫或烷基；且 R3為羥烷基。 另一項具體實施例為如上文在發明内容中所提出之式（1) 化合物，其係選自包括： 2_丁基-3-(2,3-二羥基丙基 &gt;套唑琳_4(3H)_酮；與 3-(2,3-二經基丙基）-2-曱基p奎。坐琳_4(3H)·酮。 另一項具體實施例為如上文所示之式①化合物，其中： η為1 ;Q 〇 is a fused phenyl group; 128409 - 73 - 200836743 R1 is hydrogen; R2 is hydrogen or an alkyl group; and R3 is a hydroxyalkyl group. Another specific embodiment is a compound of formula (1) as set forth above in the Summary of the Invention, which is selected from the group consisting of: 2-butyl-3-(2,3-dihydroxypropyl)&gt;4(3H)-ketone; with 3-(2,3-dipropylpropyl)-2-indenyl p-quinion. sits _4(3H).one. Another specific embodiment is as shown above a compound of formula 1 wherein: η is 1;

Q 為稠合苯基； R1為氫； R2為氫或烷基； R3 為 _R7 -N(R4 )R5 或 _R7 _N(R4 )c(〇)〇r4 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、函烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或_R5和彼兩者所連接之氮—起，形成視情況經取代之 雜環基或視情況經取代之N_雜芳基，·且 各R為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 128409 •74- 200836743 經取代之直鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式（I) 化合物，其係選自包括： [3-(2-丁基4-酮基喹唑啉-3(4H)-基）丙基]胺基甲酸第三-丁酯； [2-(2-丁基-4-酮基喹唑淋-3(4H)-基）乙基]胺基甲酸第三-丁酯； 3-(2-胺基乙基）-2-丁基喹唑啉-4(3H)-酮； 3-(3-胺基丙基）_2_丁基p奎唑琳_4(3H)-酮； , 丁基各(2-六氫吡啶小基乙基 &gt;奎唑啉_4(3H)-酮； 2_ 丁基-3-(3•六氫吡啶-μ基丙基 &gt;奎唑啉，3H)，；及 2_丁基-3-(3-四氫吡咯-1-基丙基）喳唑啉4(3H)-酮。 另一項具體實施例為如上文所示之式（I)化合物，其中： η為1 ; 0 〇為稠合苯基； R為氫； , R2為氫或烷基； …雜環基烧基’視情況被一或多個取代基取代，取代基 遥自包括烷基、烯基、炔基、_基、_烷基、鹵烯基、 鹵炔基、視情況經取代之環烷基、視情況經取代之環 烷基烷基、視情況經取代之環烷基烯基、視情況經取 代之環烷基炔基、視情況經取代之芳基、視情況經取 代之芳烷基、視情況經取代之芳烯基、視情況經取代 之芳炔基、視情況經取代之雜環基、視情況經取代之 雜環基烷基、視情況經取代之雜環基烯基、視情況經 128409 -75 - 200836743 取代之雜環基炔基、視情況經取代之雜芳基、視情況 經取代之雜芳烷基、視情況經取代之雜芳基烯基、視 情況經取代之雜芳基炔基、-R6 -CN、-R6 -N02、-R6 -OR5、 -R6-0C(0)R4 &gt; -R6-OS(0)2R4 . -R6-C(0)R4 &gt; -R6-C(0)0R4 ^ -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)OR4、-R6-N(R5)C(0)N(R4)R5、_R6-N(R5)S(0)tR4 、-R6-N[S(0)tR4]2 、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 、 -R6 -N(R5 )C(=NR5 )N(R4 )CN 、 -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 &gt;C(0)OR4 、 -R6-N(R5)-R7-N(R4)R5、-R6-N=C(OR4)R5、-R6_n=C(R4)R5、 -R6-N(R5)-R6-0R5、-R6_s(〇)pR4 及 R6 s(〇)tN(R4 见5，其中各 P係獨立為〇，1或2，且各t係獨立為i或2 ; 各R4與R5係獨立選自包括氫、烧基、稀基、快基、鹵烧基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 、、二取代之環院基烧基、視情況經取代之芳基、視情況 ί 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R與R5和彼兩者所連接之氮一起，形成視情況經取代之 Ν-雜環基或視情況經取代之Ν-雜芳基； R為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 ^視6況經取代之直鏈或分枝狀次烯基鏈或視情況 7、、、二取代之直鏈或分枝狀次快基鏈；且 二直鏈或刀枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 128409 -76- 200836743 鏈或分枝狀次炔基鏈。 ^項具體貫施例為如上文在發明内容中所提出之式（1) 匕。其係為丁基娜分甲基四氫峨略-2-基）乙基]峻唾 啉-4(3H)^ii。 另-項具體實施例為如上文所示之式⑴化合物，· JQ 為 1 ; ·Q is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or an alkyl group; R3 is _R7-N(R4)R5 or _R7_N(R4)c(〇)〇r4; each R4 and R5 are independently selected from Including hydrogen, alkyl, alkenyl, alkynyl, alkenyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted Aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl Or _R5 and the nitrogen to which they are attached, form an optionally substituted heterocyclic group or an optionally substituted N_heteroaryl group, and each R is a direct bond, optionally substituted A linear or branched subalkyl chain, optionally substituted straight or branched subalkenyl chain or, as appropriate, a linear or branched subalkynyl chain substituted by 128409.74-200836743. Another specific embodiment is a compound of formula (I) as set forth above in the Summary of the Invention, which is selected from the group consisting of: [3-(2-butyl 4-ketoquinazolin-3(4H)-yl) Propyl]carbamic acid tert-butyl ester; [2-(2-butyl-4-ketoquinazolin-3(4H)-yl)ethyl]carbamic acid tert-butyl ester; 3 -(2-Aminoethyl)-2-butylquinazoline-4(3H)-one; 3-(3-Aminopropyl)_2-butyl p-quinazoline-4(3H)-one ; , butyl each (2-hexahydropyridine small ethyl group &gt; quinazoline 4 (3H)-one; 2 - butyl-3-(3 • hexahydropyridine - μ propyl &gt; quinazoline , 3H), and 2-butyl-3-(3-tetrahydropyrrole-1-ylpropyl)oxazoline 4(3H)-one. Another specific embodiment is a formula as shown above ( I) a compound wherein: η is 1; 0 〇 is a fused phenyl group; R is hydrogen; and R 2 is hydrogen or an alkyl group; ...heterocyclyl group is optionally substituted by one or more substituents, substituents Distinguishable from alkyl, alkenyl, alkynyl, yl, _alkyl, haloalkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally Substituted cycloalkylalkenyl, as appropriate Cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, Optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, heterocyclylalkynyl, as appropriate, substituted by 128409-75 - 200836743, optionally substituted heteroaryl, optionally Substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, -R6-0C (0 R4 &gt; -R6-OS(0)2R4 . -R6-C(0)R4 &gt; -R6-C(0)0R4 ^ -R6 -C(0)N(R4 )R5, -R6 -N( R4)R5, -R6 -N(R5)C(0)R4, -R6-N(R5)C(0)OR4, -R6-N(R5)C(0)N(R4)R5, _R6-N (R5)S(0)tR4, -R6-N[S(0)tR4]2, -R6 -N(R5)C(=NR5 )N(R4 )R5 , -R6 -N(R5 )C(= NR5 )N(R4 )CN , -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 &gt;C(0)OR4 , -R6-N(R5)-R7-N(R4) R5, -R6-N=C(OR4)R5, -R6_n=C(R4)R5, -R6-N(R5)-R6-0R5, -R6_s(〇)pR4 and R6 s(〇)tN(R4 5, wherein each P system is independently 〇, 1 or 2, and each t system is independently i or 2; R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, dilute, fast radical, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally, disubstituted ring. Alkyl group, optionally substituted aryl group, optionally substituted aralkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl group, optionally substituted heteroaryl group And optionally substituted heteroarylalkyl; or R together with R5 and the nitrogen to which they are attached, form an optionally substituted anthracene-heterocyclic group or an optionally substituted anthracene-heteroaryl; Direct-bonded, optionally substituted linear or branched sub-alkyl group, as defined by a linear or branched sub-alkenyl chain, or a linear or branched, optionally substituted, 7, or disubstituted a fast-chain chain; and a two-linear or cleavage-like alkylene chain, a linear or branched sub-alkenyl chain or a straight 128409-76-200836743 chain or a branched subalkynyl chain. The specific embodiment is the formula (1) as set forth above in the Summary of the Invention. It is a butyl group of methyltetrahydroindol-2-yl)ethyl]trisporin-4(3H)^ii. Another specific embodiment is a compound of formula (1) as shown above, JJ is 1;

Q 〇為稠合苯基； R1 為氫、鹵基、-R6_N〇2 或 _r6-n(r4)r5 ; R2為烷基或芳基； R為方基，視情況被一或多_取代基取代，取代基選自包 括燒基、烯基、快基、^基、_垸基、齒稀基、齒快 土視^况經取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代 之壞烧基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 方炔基、視情況經取代之雜環基、視情況經取代之雜 %基烷基、視情況經取代之雜環基烯基、視情況經取 代之雜％基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、-R6-CN、-R6-N02、-R6-〇R5、 -R6-0C(0)R4、-R6_os⑼2r4、r6 -C(〇)r4、r6 _c⑼〇r4、 -R -C(0)N(R4)R5、_R6-N(R4)R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5 )C(0)0R4 &gt; -R6-N(R5 )C(0)N(R4 )R5 - -R6-N(R5 )S(0)t R4 128409 •77- 200836743 -R6-N[S(0)tR4]2 &gt; -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5&gt; C(=NR5)N(R4)CN、-R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4、 -R6-N(R5)-R7-N(R4)R5、-R6 养C(OR4)R5、-r6_N=c(R4)R5、 p係獨立為〇，1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 备烧基、烧氧烧基、視情況經取代之環烧基、視情況 經取代之環烧基烧基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鍵、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式（I)化合物，其中· η 為 1 ; ’、 Q、. 為稠合笨基； R1為氫、鹵基、; R為垸基或芳基； 128409 • 78 - 200836743 R3為苯基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、_基、_烷基、_烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烷基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基…R6-CN、-R6-N〇2、H〇r5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 . -R6-C(0)R4 &gt; -R6-C(0)〇R4 . -R6-C(0)N(R4)R5、-R6_n(R4)r5、r6_n(r5)c(〇)r4、 -R6-N(R5)C(0)0R4 . -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 -R -N[S(〇)tR4]2 &gt; -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5)-C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5)-R7-N(R4)R5、_R6 养c(OR4)R5、-R6-N=C(R4)R5、 必-專5)此视5、_1^-8叫114及_116名(〇\寧4)115，其中各 p係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 、、二取代之環烧基烧基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 128409 -79- 200836743 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 从雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次快基鏈。 / 另一項具體實施例為如上文在發明内容中所提出之式① 化合物，其係選自包括： 3-(4-胺基苯基）-2-丁基-6-氯基p奎唾p林-4(3H)-g同； 3-(4-胺基苯基）-2-丁基-7-氯基喹唑啉-4(3H)-酮； 2-丁基-7-石肖基-3-苯基峻峻4 -4(3H)-_ ; 2- 丁基-6-硝基-3-苯基喳唑啉·4(3Η)-酮； 7-胺基-2-丁基-3-苯基喳唑啉-4(3Η&gt;酮； 6-胺基-2-丁基各苯基喹唑啉-4(3Η)-酮； 3_(4-嗎福淋冬基苯基）-2-{3-[3-(三氟曱基）苯氧基]苯基奎唑琳 -4(3Η)-酮；及 3- (4-嗎福淋-4-基苯基）-2-苯基邊。坐琳-4(311)-|同。 另一項具體實施例為如上文所示之式（I)化合物，其中： η為1至4 ; Q . 為稠合雜芳基， 各R1係獨立選自包括氫、烧基、稀基、快基、_基、_燒 128409 -80 - 200836743 基、i烯基、函炔基、環烷基、環烷基烷基、環烷基 浠基、環烧基快基、芳基、芳烧基、芳烯基、芳炔基、 雜環基、雜環基烧基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烧基、雜芳基豨基、雜芳基炔基、-R6_CN、 -R6-N02 &gt; -R6-〇R5 &gt; -R6-N(R4)R5 ^ -R6-S(0)pR4 &gt; -R6-C(0)R4 ' -R6-C(S)R4、-R6-C(R4)2C(0)R5、-R6-C(0)0R4、-r6-〇c(〇)r4、 -r6-c(s)or4 、-r6-c(o)n(r4)r5 、_r6-c(s)n(r4)r5 、 -r6-n(r5)c(o)r4、-R6-N(R5)C(S)R4、-r6-n(r5)c(o)or4、 -R6-N(R5)C(S)OR4、-R6-N(R5)C(0)N(R4)R5、-R6_N(R5)c(s)_ N(R4)R5、-R6-N(R5)S(〇)tR4、-R6-N(R5)s(〇)tN(R4)R5、 -R6 -S(0)t N(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 _N(R5 &gt; C(N=C(R4)R5)N(R4)R5，其中各!)係獨立為〇，1或2，且各t 係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起’可形成稠合環，選自環烷基、芳基、雜環基或雜 方基’而其餘R1基團’若存在則均如上述； R2為氫、烷基、烯基、炔基、！|烷基、_烯基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烧基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烷基、烯基、炔基、！I烷基、鹵烯基、_炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 快基、芳基、芳烧基、芳烯基、芳快基、雜環基、雜 128409 -81 - 200836743 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜蒡基炔基、hn(R4)r5,或 -r6-n(r4)c(o)or4 ; ’ 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環 基烷基、雜環基烯基、雜環基炔基、雜芳基、雜 芳烷基、雜芳基烯基或雜芳基炔基可視情況被一 或多個取代基取代，取代基選自包括烷基、烯基、 炔基、鹵基、ii烷基、_烯基、_炔基、視情況 經取代之環烷基、視情況經取代之環烷基烷基、 視情況經取代之環烧基烯基、視情況經取代之環 烷基炔基、視情況經取代之芳基'視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取 代之芳炔基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜環基稀 基、視情況經取代之雜環基炔基、視情況經取代 之雜芳基、視情況經取代之雜芳烷基、視情況經 取代之雜芳基埽基、視情況經取代之雜芳基炔基、 -R6 -CN ^ -R6 -N〇2 - -R6 -OR5 &gt; -R6 -0C(0)R4 &gt; -R6 -0S(0)2 R4 、-R6-C(0)R4、-R6_C(0)0R4、-R6-C(〇)n(r4)r5、 -R6-N(R4)R5 ^ -R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(0)〇R4 ^ -R6 -N(R5 )C(0)N(R4 )R5 、 -R6-N(R5 )S(0)tR4 、 -R6-N[S(0)tR4]2 - -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5)-C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)- 128409 -82- 200836743 C(〇)〇r4 λ -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 . -R6-n=c(r4)r5、-R6-N(R5)-R6_OR5、_R6-S(0)PR4 及 -R6-S(〇)tN(R4)R5，其中各p係獨立為〇, 1或2，且各 t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、函烷基、 經烧基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 ,. 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 i ,. R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文所示之式①化合物，其中： η為1 ; 0 〇為稠合雜芳基；Q 〇 is a fused phenyl group; R1 is hydrogen, a halogen group, -R6_N〇2 or _r6-n(r4)r5; R2 is an alkyl group or an aryl group; R is a square group, which is optionally substituted by one or more _ Substituted, the substituent is selected from the group consisting of an alkyl group, an alkenyl group, a fast group, a group, a fluorenyl group, a dentate group, a ring-shaped alkyl group substituted with a cycloalkyl group, and optionally a substituted cycloalkyl alkane. Substituted, optionally substituted cycloalkenyl alkenyl, optionally substituted glysyl alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, Optionally substituted alkynyl, optionally substituted heterocyclic, optionally substituted heteroenylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroalkynyl , optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6- N02, -R6-〇R5, -R6-0C(0)R4, -R6_os(9)2r4, r6 -C(〇)r4, r6 _c(9)〇r4, -R -C(0)N(R4)R5, _R6-N( R4) R5, -R6 - N(R5)C(0)R4, -R6-N(R5)C(0)0R4 &gt; -R6-N(R5)C(0 N(R4)R5 - -R6-N(R5)S(0)t R4 128409 •77- 200836743 -R6-N[S(0)tR4]2 &gt; -R6-N(R5 )C(=NR5 N(R4)R5 - -R6-N(R5&gt; C(=NR5)N(R4)CN, -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0 ) 0R4, -R6-N(R5)-R7-N(R4)R5, -R6 raise C(OR4)R5, -r6_N=c(R4)R5, p is independently 〇, 1 or 2, and each t Is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, alkyl, anthracyl, optionally substituted cycloalkyl, Substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally Substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclyl or optionally substituted N-hetero Aryl; each R6 is a direct bond, optionally substituted straight or branched subalkyl bond, optionally substituted straight or branched subalkenyl chain or optionally substituted straight chain or Branched subalkynyl chain; and R7 is linear or a dendritic alkyl chain, a linear or branched subalkenyl chain or a linear or branched hypoalkynyl chain. Another specific embodiment is a compound of formula (I) as shown above, wherein Is 1; ', Q,. is a fused base; R1 is hydrogen, halo; R is fluorenyl or aryl; 128409 • 78 - 200836743 R3 is phenyl, optionally substituted by one or more substituents a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, —yl, —alkyl, —alkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, Optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally as appropriate Substituted aralkynyl, optionally substituted heterocyclic, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, Substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryl Base... R6-CN, -R6-N〇2, H〇r5, -R6-0C(0)R4 &gt; -R6-0S(0)2R4 . -R6-C(0)R4 &gt; -R6-C (0) 〇 R4 . -R6-C(0)N(R4)R5, -R6_n(R4)r5, r6_n(r5)c(〇)r4, -R6-N(R5)C(0)0R4 . R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 -R -N[S(〇)tR4]2 &gt; -R6-N(R5 ) C(=NR5)N(R4)R5 - -R6-N(R5)-C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N( R4)-C(0)0R4 ^ -R6-N(R5)-R7-N(R4)R5, _R6 raise c(OR4)R5, -R6-N=C(R4)R5, must-specific 5) Depending on 5, _1^-8 is called 114 and _116 (〇\宁4) 115, where each p is independent of 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected Including hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally, disubstituted cycloalkyl, optionally Substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally 128409-79- 200836743 Substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached, formed as appropriate a heterocyclic group or an optionally substituted N-heteroaryl group; each R6 is a direct-bonded, optionally substituted straight or branched alkylene chain, optionally substituted straight or branched An alkenyl chain or an optionally substituted linear or branched subalkynyl chain; and R7 is a linear or branched subalkyl chain, a straight or branched subalkenyl chain or a straight chain or a branched The fast base chain. / another specific embodiment is a compound of formula 1 as set forth above in the Summary of the Invention, which is selected from the group consisting of: 3-(4-aminophenyl)-2-butyl-6-chloro-p-purine P-lin-4(3H)-g is the same; 3-(4-aminophenyl)-2-butyl-7-chloroquinazolin-4(3H)-one; 2-butyl-7-stone 3-phenyl phenyl 4 - 4(3H)-_ ; 2-butyl-6-nitro-3-phenyloxazoline·4(3Η)-one; 7-amino-2-butyl 3-phenyloxazoline-4 (3Η&gt;ketone; 6-amino-2-butyl-phenyl quinazolin-4(3Η)-one; 3_(4-isfolinylphenyl) -2-{3-[3-(Trifluoromethyl)phenoxy]phenyl quinazoline-4(3Η)-one; and 3-(4-moff-4-ylphenyl)-2 -Phenyl side. Selenium-4(311)-|同. Another specific embodiment is a compound of formula (I) as shown above, wherein: η is from 1 to 4; Q. is a fused heteroaryl group. , each R1 is independently selected from the group consisting of hydrogen, alkyl, dilute, fast radical, _ group, _128128-80 - 200836743, i-alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, ring Alkyl fluorenyl, cycloalkyl radical, aryl, arylalkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, Cycloalkynyl, heteroaryl, heteroarylalkyl, heteroaryl fluorenyl, heteroarylalkynyl, -R6_CN, -R6-N02 &gt; -R6-〇R5 &gt; -R6-N(R4)R5 ^ -R6-S(0)pR4 &gt; -R6-C(0)R4 ' -R6-C(S)R4, -R6-C(R4)2C(0)R5, -R6-C(0)0R4 , -r6-〇c(〇)r4, -r6-c(s)or4, -r6-c(o)n(r4)r5, _r6-c(s)n(r4)r5, -r6-n( R5)c(o)r4, -R6-N(R5)C(S)R4, -r6-n(r5)c(o)or4, -R6-N(R5)C(S)OR4, -R6- N(R5)C(0)N(R4)R5, -R6_N(R5)c(s)_ N(R4)R5, -R6-N(R5)S(〇)tR4, -R6-N(R5) s(〇)tN(R4)R5, -R6 -S(0)t N(R4)R5, -R6 -N(R5)C(=NR5 )N(R4 )R5 and -R6 _N(R5 &gt; C (N=C(R4)R5)N(R4)R5, wherein each !) is independently 〇, 1 or 2, and each t is independently 1 or 2; or two adjacent R1 groups and their The directly linked carbon or heterocyclic atoms together 'may form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl' and the remaining R1 groups, if present, are as described above; R2 is hydrogen, Alkyl, alkenyl, alkynyl,! |alkyl, alkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, arylalkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclyl Alkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is hydrogen, alkyl, alkenyl, alkynyl, ! Ialkyl, haloalkenyl, ynkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkyl fast radical, aryl, arylalkyl, aralkenyl, aromatic Fast radical, heterocyclic group, heteropoly 128409-81 - 200836743 cycloalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heterodecynyl , hn(R4)r5, or -r6-n(r4)c(o)or4 ; ' wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl Alkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroaryl The alkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, iialkyl, alkenyl, ethynyl, optionally substituted cycloalkyl , optionally substituted cycloalkylalkyl, optionally substituted cycloalkylenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl 'optionally substituted aralkyl , substituted alkenyl, as appropriate, replaced by circumstances Alkynyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl alkynyl, optionally substituted Heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaryl fluorenyl, optionally substituted heteroarylalkynyl, -R6 -CN^-R6-N〇2 - -R6 -OR5 &gt; -R6 -0C(0)R4 &gt; -R6 -0S(0)2 R4 , -R6-C(0)R4, -R6_C(0)0R4, -R6-C(〇)n(r4 )r5, -R6-N(R4)R5^-R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(0)〇R4 ^ -R6 -N(R5 )C(0 N(R4)R5, -R6-N(R5)S(0)tR4, -R6-N[S(0)tR4]2 - -R6-N(R5)C(=NR5 )N(R4 )R5 - -R6-N(R5)-C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)- 128409 -82- 200836743 C(〇 ) 〇r4 λ -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 . -R6-n=c(r4)r5, -R6-N(R5) -R6_OR5, _R6-S(0)PR4 and -R6-S(〇)tN(R4)R5, wherein each p is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 Is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkenyl, alkyl, alkoxyalkyl, optionally substituted cycloalkyl, as appropriate a substituted cycloalkylalkyl group, optionally substituted aryl group, optionally, substituted aralkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclic group, and optionally substituted Substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclyl or optionally substituted N —heteroaryl; each R 6 is a direct bond, optionally substituted straight or branched alkylene chain, optionally substituted straight or branched subalkenyl chain or optionally substituted a chain or a branched subalkynyl chain; and i,. R7 is a linear or branched alkylene chain, a linear or branched secondary alkenyl chain or a linear or branched cisynyl chain. Another specific embodiment is a compound of formula 1 as shown above, wherein: η is 1; 0 〇 is a fused heteroaryl;

Rl為氫或烧基； R2為氫或烷基； r3為芳基，視情況被一或多個取代基取代，取代基選自包 128409 -83- 200836743 括烷基、烯基、炔基、i基、ι|烷基、鹵烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烧基、視情況經取代之環烧基婦基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烧基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、-R6以〇2、、 -R6-0C(0)R4、-R6-〇S(〇)2R4、-R6_c(q)r4、-R6_c(〇)〇r4、 -R6-C(0)N(R4)R5、.R6-N(R4)R5 . -R6-N(R5)C(0)R4 &gt; 'R -N(R5 )C(〇)〇R4 - -R6-N(R5 )C(0)N(R4 )R5 &gt; -R6-N(R5 )S(0)tR4 -R -N[S(0)tR4]2 - -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5)- C(=服5)N(R4)CN、-R6-N(R5)C[=NC(0)0R4]-N(R4K：⑼OR4、 _R6-N(R5&gt;R7_N(R4)R5、_r6-N=c(〇r4)r5、_r6 .c(r4)r5、 -R6-N(R5)-R6-〇r5、-R6_s(〇)pR4 及 r6 _s(〇㈣r4)r5 ^ P係獨立為〇, 1或2，且各1係獨立為丨或二； 各R4與R5係獨立選自包括氫、燒基、烯基、炔基、_烧基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 128409 • 84 - 200836743 或R4與R5和彼兩者所速垃々^ ^ s 虱一起，形成視情況經取代之 雜環基或視情況經取代之N·雜芳基； 各R6為直接鍵結、視愔 、 視^况經取代之直鏈或分枝狀次烷基 鏈視f月况經取代之直鏈或分枝狀次稀基鍵或視情況 經取代之直鏈或分枝狀次炔基鏈；且 r為直鏈或分枝狀錢錢、直㈣分枝狀次縣鍵或直 鏈或分枝狀次炔基鏈。 其中R1 is hydrogen or alkyl; R2 is hydrogen or alkyl; r3 is aryl, optionally substituted by one or more substituents selected from the group consisting of 128,409-83-200836743 including alkyl, alkenyl, alkynyl, I-based, i-alkyl, haloalkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkyl, optionally Substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aryl, optionally substituted aralkenyl, optionally substituted alkynyl, optionally substituted heterocyclic Substituent, optionally substituted heterocyclic alkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted Aromatic alkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, -R6 as 〇2, -R6-0C(0)R4, -R6-〇S ( 〇) 2R4, -R6_c(q)r4, -R6_c(〇)〇r4, -R6-C(0)N(R4)R5, .R6-N(R4)R5 . -R6-N(R5)C( 0) R4 &gt; 'R -N(R5 )C(〇)〇R4 - -R6-N(R5 )C(0)N(R4 )R5 &gt; -R6-N(R 5)S(0)tR4 -R -N[S(0)tR4]2 - -R6-N(R5 )C(=NR5 )N(R4 )R5 - -R6-N(R5)- C(=服5) N(R4)CN, -R6-N(R5)C[=NC(0)0R4]-N(R4K:(9)OR4, _R6-N(R5&gt;R7_N(R4)R5, _r6-N=c(〇 R4)r5, _r6 .c(r4)r5, -R6-N(R5)-R6-〇r5, -R6_s(〇)pR4 and r6 _s(〇(tetra)r4)r5 ^ P are independent 〇, 1 or 2, And each of the 1 series is independently 丨 or 2; each of R 4 and R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted naphthenes. a cycloalkylalkyl group, optionally substituted aryl group, optionally substituted aralkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl group, Optionally substituted heteroaryl and optionally substituted heteroaralkyl; 128409 • 84 - 200836743 or R4 and R5 together with the two of them, form an optionally substituted heterocyclic ring a N-heteroaryl group substituted or substituted as appropriate; each R6 is a linear or branched sub-alkyl chain which is directly bonded, visually or visually substituted Dendritic sub-primary bond or as appropriate a linear or branched subalkynyl chain; and r is a linear or branched form of money, a straight (tetra) branched sub-counter bond or a linear or branched subalkynyl chain. among them

另一項具體實施例為如上文所示之式(I)化合物 η為1 ; 為稠合雜芳基； Θ R1為氫或烧基； R2為氫或烷基； R為苯基’視情況被—或多個取代基取代，取代基選自包 括-R6-CN、-R6_N〇2、_R6_n(r5)c(〇)〇rhn(r4)r5 · 各R與R5係獨立選自包括氳、燒基、烯基、快基、_燒基、 經烧基、燒氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N-雜芳基；且 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 128409 -85 - 200836743 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈。 另一項具體實施例為如上文在發明内容中所提出之式⑴ 化合物，其係選自包括： 3-(4-胺基苯基）-2·丁基p比唆并[2,3-d]嘴咬_4(3H)-_ ; 3-(4-胺基苯基）-2-丁基喋啶-4(3H)-酮； 3-(4-胺基苯基）-2-丁基遠吩并[2,3-d]嘧啶-4(3H)·酮； 3-(4-胺基苯基）-2-丁基嘧吩并[3,2-d]嘧啶-4(3H)-酮；及 3-(4·胺基苯基）-2-丁基-7-甲基嘧吩并[3,2-d]嘧啶-4(3H&gt;酮。 另一項具體實施例為如上文在發明内容中所提出之式⑴ 化合物，其係選自包括·· [4-(2-丁基_4_酮基吡啶[2,3-d]嘧啶-3(4H)-基）苯基]胺基甲酸第三 -丁酯； [4_(2叮基斗酮基喋啶-3(4H)-基）苯基]胺基甲酸第三叮s旨；及 3-(4-胺基苯基）_2_丁基吡啶并[3,4_d]嘧啶-4(3H)_酮。 本發明之另一項具體實施例為如上文在發明内容中所提 出之式（1-1)化合物。 本發明之另一項具體實施例為在哺乳動物較佳為人類 中，治療、預防或改善疾病或症狀之方法，其中疾病或症 狀係4自包括疼痛、抑鬱、心血管疾病、呼吸道疾病與精 神病學疾病及其組合，且其中此方法包括對有需要之哺乳 動物投予治療上有效量之如上述本發明化合物之具體實施 例’為其立體異構物、對掌異構物、互變異構物或其混合 物，或其藥學上可接受之鹽、溶劑合物或前體藥物，或一 128409 -86- 200836743 種wl、且口物，其包含如上述之本發明化 異構物、對掌里播从 物為其立體 上可接受之Γ 互變異構物或其混合物；或其藥學 賦形劑。…劑合物或前體藥物’及藥學上可接受之 此具體Λ施例之_項具體實施例係為其 選自包括神Μ、虑届沾☆— 用4瓦狀係 '、病原性疼痛、炎性疼痛、內臟 痛、化學療法疼痛、指疗、皮广 # 瓜症疼 、 知知疼痛、手術疼痛、手術後疼痛、 ”、痛、分娩疼痛、神經發生性膀胱、龍性結腸炎、 ’fe性，痛、持續性疼痛、末梢媒介之疼痛、中枢媒介之疼 痛、慢性頭痛、偏頭痛、寶 ' 、 雨貝居1口頭痛、緊張頭痛、幻推胎 疼痛、末梢神經損傷及其組合。 心 此具體實施例之另—項具體實施例係為其中疾病或症狀 係選自包括與HIV有關聯之疼痛、聰治療所引致之神經 病、二又神經痛、癌療後神經痛、正常疼痛、熱敏感性、 局部肉狀瘤病、刺激性腸徵候鎮、克隆氏病、與多發性硬 化(MS)有關聯之疼痛、肌萎縮性側索硬化(綱、糖尿病惠 者之神經病、末梢神經病、關節炎、風濕性關節炎、骨I 節炎、動脈粥瘤硬化、陣發性肌緊張不足、肌無力徵候簇、 肌強直、惡性高熱、膽囊纖維變性、假醛固酮過多症、橫 紋肌溶解、曱狀腺機能減退症、兩極抑鬱、焦慮、精神分 裂症、鈉通道毒素相關疾病、家族性肢端紅痛病、原發性 肢端紅痛病、家族性直腸疼痛、癌症、癲癇、部份與I般 緊張發作、不安寧腳部徵候簇、節律不齊、纖維肌痛、在 因中風所造成之絕血狀態下之神經保護、青光眼或神經損 128409 -87- 200836743 傷、快速節律不齊、心房纖維顫動及心室纖維顏動。 本《明之另一項具體實施例為—種在哺乳動物較佳 藉由在該錢動物中抑制離子通量經過電心賴性 納通道以治療疼痛$ t、、土 ^ ^ 乳動物μ 包括對有需要之哺 礼動物技予治療上有效量之如上述本發明化合物之 ::’為其：體異構物、對掌異構物、互變異構物或其： 2 &lt;其樂學上可接受之鹽、溶劑合物或前體藥物，或 -種醫藥組合物，其包含如上述之本發明化合物為並立 :異構物:對掌異構物、互變異構物或其混合物；或其藥 予上可接党之鹽、溶劑合物或前體藥物，及藥學上可接受 之賦形劑。 来本《月之另-項具體貫施例為_種在哺乳動物較佳為人 類中，治療或預防高膽固醇血症之方法，其中此方法包括 對有需要之哺乳動物投予治療上有效量之如上述本發明化 合物之具體實施例，為其立體異構物、對掌異構物、互變 異構物或其混合物，或苴雖墨 — U予上可接受之鹽、溶劑合物或 :你樂物，或一種醫藥組合物’其包含如上述之本發明化 2 :為其立體異構物、對掌異構物、互變異構物或其混 叫勿$其藥學上可接文之鹽、溶劑合物或前體藥物，及 樂學上可接受之賦形劑。 * t月之另J員具體實施例為-種在哺乳動物較佳為人 痛中’治療或預防良性攝護腺增生之方 括物要之哺乳動物投予治療上有效量之如上述本發； 化口物之具體實施例’為其立體異構物'對掌異構物、互 128409 -88· 200836743 變㈣物或其混合物，或其藥學上可接受之鹽、溶劑合物 或前體藥物，或—種醫藥組合物，其包含如上述之本發明 :匕口物’為其立體異構物、對掌異構物、互變異構物或其 物’或其藥學上可接受之鹽、溶劑合物或前體藥物， 及藥學上可接受之賦形劑。 本發明之另-項具體實施例為—種在嗔乳動物較佳為人 類中，治療或預防瘙赛病之方法，其中此方法包括對有需 要之哺乳動物投予治療上有效量之如上述本發明化合物之 具體實施例，為其立體異構物、對掌異構物、互變異構物 或其混合物，或其藥學上可接受之鹽、溶劑合物或前體率 物，或一種醫藥組合物，其包含如上述之本發明化合物， 為其ί體異構物、對掌異構物、互變異構物或其混合物； 或’、藥予上可接文之鹽、溶劑合物或前體藥物，及 可接受之賦形劑。 μ 本發明之另-項具體實施例為一種在 類中’治療或預防癌症之方法，其中此方法包括對有= 之“動物投予治療上有效量之如上述本發明化合物之具 ==4其立體異構物、對掌異構物、互變異構物或 条于上了接文之鹽、溶劑合物或前體藥物， 或一種醫藥組合物，其包含如上述之本發明化合物，為盆 亡體異構物、對掌異構物、互變異構物或其混合物；或2 樂學上可接受之鹽、溶劑合物或前體藥物’及藥學上桩 受之賦形劑。 接 本發明之另一項具體實施例為一種在哺乳動物之細胞中 128409 -89- 200836743 I低離子通量經過„依賴性㈣道之方法，1中 包括使細胞與如上述本發 存、 去 體異構物、對掌異構物、互變显槿物^、Η ^ “、、 其藥學上可接受之…”人“構物或其混合物，或 I ^姻合物或前體藥物。 本發明化合物之特殊具體實施例係更詳 (I)化合物之製備中。 义於下文式 本發明化合物之利用性與測試 ::明化合物會在喷乳動物中，尤其是在類中調 m制離子通量經過錢㈣性鈉通道。任何此種調制， 一、係為部份或完全抑制或預防離子通量，於本文中有 時係被稱為，，阻斷”，而相應化合物為&quot;阻斷劑&quot;。一般而言， ，發明化合物會調制納通道之活性向下，抑制納通道之電 [依賴I·生活性，及/或降低或預防納離子通量越過細胞膜， 其方式是預防鈉通道活性，譬如離子通量。 ' 本务明化合物會抑制離子通量經過電壓依賴性納通道。 料化合物較佳為納通道之狀態或頻率依賴性改變劑，對 :止/密閉狀態具有低親和力’而對失活狀態具有高親和 。，等化合物可能會與位於通道之鈉傳導孔隙之内腔中 之重疊位置交互作用’類似關於其他狀態依 斷劑所述(Ce疏，S.等人，心文以之料…此等^ 物亦可能會與内腔外部之位置交互作用’且對於納離子傳 導故過通道孔隙具有異位作用。 、任何此等結果最終可負責藉由此等化合物所提供之整體 治療利益。 128409 -90- 200836743 因此，本纟明化合物為納通道阻_，I μu❹ 動物較佳為人類及其他生物體中用於治療疾病與症狀，包 括其係為逑行電壓依賴性鈉通道生物學活性之結果，或其 可藉由調制電壓依賴性鈉通道生物學活性而被改善之所； 人類疾病與症狀。 如本文定義，鈉通道所媒介之疾病或症狀係指在哺乳動 車父佳為人類中，於調制鈉通道時會被改善之疾病或症狀， 且包括但不限於疼痛，中枢神經症狀，譬如痛痛、声慮、 =及兩極疾病；心血管症狀，譬如節律不齊、心房纖維 ，員及心室纖維顫動；神經肌肉症狀，譬如不安寧腳部徵 ’矣族與肌肉麻痒或破傷風；抵抗中風、神經損傷及多發性 硬化神經保護；及通道病，嬖 疼痛徵候箱。 與豕族性直腸 因此，本發明係關於化合物，醫藥組合物，及使 化合物與醫藥組合物以在哺乳動物較佳為人4 、音#狀a 礼切奶平乂1土為人類中治療鈉通 =广疾病之方法，且較佳為相關於疼痛之疾病，中樞 :經:狀’譬如痛痛、焦慮、抑繫及兩極疾病；心血管症 節律不齊、心房纖維顏動及心室纖維顏動；神經 y二’譬如不安寧腳部徵候襄與肌肉麻痺或破傷風； 神經損傷及多發性硬化之神經保護；及通道病， L:種：痛病與家族性直腸疼痛徵候蔟，其方式是對需 要此種治療之哺乳動物，較佳為人 道阻斷劑調制（尤其是抑制㈣。、X予有政置之納通 因此’本發明係提供治療哺乳動物或保護哺乳動物免於 128409 -91 - 200836743 發展鈉通道所媒介疾病（尤其是疼痛）之方法，其包括對有 需要之哺乳動物’尤其是人類，投予治療上有效量之本發 明化合物或包含本發明化合物之醫藥組合物，纟中化合物 係調制一或多種電壓依賴性鈉通道之活性。 本發明化合物在媒介，尤其是抑制鈉通道離子通量上之 -般數值，可使用下文在生物學檢測段落中所述之檢測測 定。或者，化合物在治療症狀與疾病上之一般數值，可在 用於註實化合物治療疼痛功效之工業標準動物模式中破 立。人類神經病原性疼痛症狀之動物模式已被發展，其會 造成可重現之感官短缺（感覺異常、痛覺過敏及自發性疼 痛），歷經持續之一段時間，其可藉由感官測試評估。藉由 建立所存在機械、化學及溫度所引致之感覺異常與痛覺過 敏之程度，在人類中所發現之數種生理與病理症狀可被製 作模型，允許評估藥療法。 在末梢神經損傷之大白鼠模式中，於受傷害神經中之異 位活性，係相應於疼痛之行為跡象。在此等模式中，鈉通 道阻斷劑與局部麻醉劑利多卡因之靜脈内應用，可在不會 衫響一般行為與運動神經功能之濃度下壓抑異位活性且逆 轉觸覺感覺異常（Mao, J·與 Chen，LL，(2000)，87 : 7-17)。在 此等大白鼠模式中有效劑量之體形變化比例法，係轉化成 類似在人類中經註實有效之劑量（Tandian，D丄·與Br〇se，W G , ▲咖/^〇/〇砂（1991)，74(5) ·· 949-951)。再者，以皮膚貼藥形式 應用之Lidoderm®利多卡因，目前為一種供疱疹後神經痛用 之 FDA 許可治療藥物（Devers，A·與 Glaler，B.S·, C/加.J·(2000)， 128409 -92- 200836743 16(3) : 205-8) 〇 痛納二道二媒介之疾病或症狀亦包括與HIV有關聯之疼 二、二療所引致之神經病、三又神經痛、舌與咽神經 ^、^之神_、肥胖病痛楚、丘腦損傷、 、自身免疫疾病、氣喘、藥瘾(例如阿片製劑、苯并 二氮七圜、安非他命、料鹼、酒精、丁燒吸人）、阿耳滋 海默氏病、癡呆症、與老化有關聯之記憶力減弱、K_koff =蔟、再狹窄、尿機能障礙、失禁、巴金生氏病、腦血 “巴血、神經官能症、胃腸疾病、鐮狀細胞貧血病、移植 排斥、心臟衰竭、心肌梗塞、再灌注損傷、間歇性跋行、 絞痛、搐搦、呼吸病症、大腦或心肌絕血、長_QT徵候霧、 兒茶紛胺能多型心室搏動過速、眼部疾病、痙攣狀態、痙 f性截癱、肌病、重症肌無力、先天性肌強直性痙攀病、 π血鈣症週期性麻痒、低血鉀症週期性麻痺、禿髮、焦慮 病症、精神病症、躁狂、妄想狂、季節性情感病症、恐懼 病症、迷亂性強迫病症（〇CD)、恐怖症、孤獨癖、 铽候簇、Retts徵候簇、崩潰病症、注意力不足病症、攻擊 性、衝動控制病症、血栓形成、預箝制病、充血性心力衰 竭〜動停止、Freidrich氏失調症、脊髓與小腦失調症、脊 知病神經根病、系統性紅斑狼瘡、肉芽腫疾病、橄欖體_ 橋腦-小腦萎縮、脊髓與小腦失調症、偶發失調症、肌纖維 颁動、進行性淡蒼球萎縮、進行性核上麻痺與痙攣狀態、 外傷性腦部傷害、腦水腫、水腦損傷、脊髓損傷、神經性 厭艮、善#1、Prader-Willi徵候篇、肥胖、視神經炎、白内障、 128409 -93- 200836743 、同膜出血、絕血性視網膜病、色素性視網膜炎、急性與 k性月光眼、斑點變性、視網膜動脈閉塞、舞蹈病、亨丁 頓氏舞蹈症、大腦水腫、直腸炎、疱疹後神經痛、正常疼 ，、熱敏感性、肉狀瘤病、刺激性腸徵候窺、杜萊德徵候 族、莢納二氏综合症、Brugado徵候簇、Liddle徵候簇、克隆 氏病、多發性硬化及與多發性硬化（MS)有關聯之疼痛、肌 萎縮性側索硬化（ALS)、散佈性硬化、糖尿病患者之神經 病、末梢神經病、charC0t_Marie牙齒徵候簇、關節炎、風濕 性關節炎、骨關節炎、軟骨石灰沉著病、動脈粥瘤硬化‘; 陣發性肌緊張不；i、肌無力徵候簇、肌強直、肌強直病失 養症、肌肉營養不良、惡性高熱、膽囊纖維變性、假醛固 酮過多症、橫紋肌溶解、精神障礙、甲狀腺機能減退症、 兩極抑鬱、焦慮、、精神分裂症、鈉通道毒素相關疾病、家 族性肢端紅痛病、原發性肢端紅痛病、直腸疼痛、癌症'Another specific embodiment is that the compound η of the formula (I) as shown above is 1; is a fused heteroaryl; Θ R1 is hydrogen or alkyl; R2 is hydrogen or alkyl; R is phenyl'. Substituted by - or a plurality of substituents, the substituents are selected from the group consisting of -R6-CN, -R6_N〇2, _R6_n(r5)c(〇)〇rhn(r4)r5. Each R and R5 are independently selected from the group consisting of ruthenium, An alkyl group, an alkenyl group, a fast-radical group, a hydrazino group, a pyrolyzed group, an alkyloxyalkyl group, an optionally substituted cycloalkyl group, optionally substituted cycloalkylalkyl group, optionally substituted aryl group, Optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R Together with the nitrogen to which R5 and the two are attached, an optionally substituted N-heterocyclic group or an optionally substituted N-heteroaryl group; and each R6 is a direct bond, optionally substituted straight chain Or branched alkylidene 128409 -85 - 200836743 chain, optionally substituted straight or branched subalkenyl chain or optionally substituted straight or branched nalkenyl chain. Another specific embodiment is a compound of formula (1) as set forth above in the Summary of the Invention, which is selected from the group consisting of: 3-(4-aminophenyl)-2.butyl p-pyrene and [2,3- d] mouth bite _4(3H)-_ ; 3-(4-aminophenyl)-2-butylacridine-4(3H)-one; 3-(4-aminophenyl)-2- Butyl far-benzo[2,3-d]pyrimidin-4(3H)·one; 3-(4-aminophenyl)-2-butylsulfonyl[3,2-d]pyrimidine-4 ( 3H)-keto; and 3-(4.aminophenyl)-2-butyl-7-methylsulfeno[3,2-d]pyrimidin-4 (3H&gt; ketone. Another specific embodiment Is a compound of formula (1) as set forth above in the Summary of the Invention, which is selected from the group consisting of [4-(2-butyl-4-yl-ketopyridine [2,3-d]pyrimidin-3(4H)-yl) Phenyl]amino-carboxylic acid tert-butyl ester; [4_(2叮- keto-keto acridine-3(4H)-yl)phenyl]carbamic acid as the third 叮s; and 3-(4- Aminophenyl)_2-butylpyrido[3,4-d]pyrimidin-4(3H)-one. Another specific embodiment of the invention is the formula (1-1) as set forth above in the Summary of the Invention. Another embodiment of the invention is a method of treating, preventing or ameliorating a disease or condition in a mammal, preferably a human. Wherein the disease or symptom 4 is a combination of pain, depression, cardiovascular disease, respiratory disease and psychiatric disease, and combinations thereof, and wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of the invention as described above. DETAILED DESCRIPTION OF THE INVENTION 'is a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a 128409-86-200836743 species Wl, and a mouthful comprising the above-described oxidized isomer of the invention, a sterically acceptable hydrazine tautomer thereof or a mixture thereof; or a pharmaceutical excipient thereof The specific embodiment of the substance or prodrug and the pharmaceutically acceptable embodiment of the invention is selected from the group consisting of a sacred sputum, a sputum ☆ - a 4-watt system, a pathogenic pain, an inflammatory Pain, visceral pain, chemotherapy pain, finger therapy, skin wide # melon pain, knowing pain, surgical pain, postoperative pain, ", pain, labor pain, neurogenic bladder, colitis, 'fe sex , pain, persistent pain , pain in the peripheral media, pain in the central media, chronic headache, migraine, Bao', rain, a headache, nervous headache, magical fetal pain, peripheral nerve injury and combinations thereof. The embodiment is wherein the disease or symptom is selected from the group consisting of pain associated with HIV, neuropathy caused by Cong treatment, neuropathic pain, post-therapy neuralgia, normal pain, heat sensitivity, local sarcoidosis, Stimulating intestinal syndrome, Crohn's disease, pain associated with multiple sclerosis (MS), amyotrophic lateral sclerosis (clinical, diabetic nephropathy, peripheral neuropathy, arthritis, rheumatoid arthritis, bone I Hyperinflammation, atheroma, atherosclerosis, paroxysmal dystonia, muscle weakness syndrome, myotonia, malignant hyperthermia, gallbladder fibrosis, pseudoaldosteronism, rhabdomyolysis, hypogonadism, bipolar depression, anxiety, Schizophrenia, sodium channel toxin-related diseases, familial acral red pain, primary acral red pain, familial rectal pain, cancer, epilepsy, part I-like tension, restless foot syndrome, irregular rhythm, fibromyalgia, neuroprotection in the state of apoplexy caused by stroke, glaucoma or nerve damage 128409 -87- 200836743 Injury, rapid rhythm, Atrial fibrillation and ventricular fibrillation. Another specific embodiment of the present invention is that in mammals, it is preferred to inhibit ion flux through the electrocardiographic nanochannel to treat pain in the animal, and to treat the pain. Therapeutic animal is in need of a therapeutically effective amount of a compound of the invention as described above:: 'is: an isomer, a palmomer, a tautomer or the like: 2 &lt; An acceptable salt, solvate or prodrug, or a pharmaceutical composition comprising a compound of the invention as defined above as a conjugate: isomer: palmomer, tautomer or mixture thereof; The drug is administered as a salt, solvate or prodrug, and a pharmaceutically acceptable excipient. The present invention relates to a method for treating or preventing hypercholesterolemia in a mammal, preferably a human, wherein the method comprises administering a therapeutically effective amount to a mammal in need thereof. Specific examples of the compounds of the present invention as described above are the stereoisomers, palmomers, tautomers or mixtures thereof, or the salts, solvates or: Your pleasure, or a pharmaceutical composition, which comprises the invention 2 as described above: its stereoisomers, palmomers, tautomers or their singularities are not pharmaceutically acceptable a salt, solvate or prodrug, and a pharmaceutically acceptable excipient. * The specific example of the J member of the month is that the mammal is administered a therapeutically effective amount to treat or prevent the benign prostatic hyperplasia in a mammal, preferably in human pain. Specific examples of physicochemicals are 'stereoisomers thereof', palmier isomers, trans-128409-88·200836743, or mixtures thereof, or pharmaceutically acceptable salts, solvates or precursors thereof A pharmaceutical, or a pharmaceutical composition comprising the invention as described above: a mouthwash as its stereoisomer, palmo isomer, tautomer or a substance thereof or a pharmaceutically acceptable salt thereof , solvates or prodrugs, and pharmaceutically acceptable excipients. Another embodiment of the present invention is a method for treating or preventing rickets in a mammal, preferably a human, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount as described above Specific examples of the compound of the present invention are stereoisomers, palmomers, tautomers or mixtures thereof, or pharmaceutically acceptable salts, solvates or precursors thereof, or a pharmaceutical a composition comprising a compound of the invention as described above, as a lipomer, a palmomer, a tautomer or a mixture thereof; or a drug, a salt or a solvate thereof Prodrugs, and acceptable excipients. Another embodiment of the invention is a method of treating or preventing cancer in a class, wherein the method comprises administering to the animal "therapeutic effective amount of a compound of the invention as described above == 4" a stereoisomer, palmosome, tautomer or strip thereof, a salt, solvate or prodrug thereof, or a pharmaceutical composition comprising a compound of the invention as described above, Oral isomers, palmomers, tautomers or mixtures thereof; or 2 orally acceptable salts, solvates or prodrugs and pharmaceutically acceptable excipients. Another embodiment of the present invention is a method for the low ion flux of 128409-89-200836743 I in a mammalian cell to undergo a Dependent (four) tract, and the method 1 includes culturing the cell with the above-described hair and body Isomers, palmomers, tautomers, Η^, ", pharmaceutically acceptable ..." human "constructs or mixtures thereof, or I ^ conjugates or prodrugs. Particular specific examples of the inventive compounds are in the preparation of the compounds of more detail (I). The utility and test of the compound of the present invention in the following formula: The compound of the formula will regulate the ion flux through the money (tetra) sodium channel in the milk spray animal, especially in the class. Any such modulation, one is the department Partial or complete inhibition or prevention of ion flux, sometimes referred to herein as, "blocking", and the corresponding compound is &quot;blocker&quot;. In general, the inventive compound modulates the activity of the nanochannel down, inhibits the electrical conductivity of the nanochannel [depending on I. life, and/or reduces or prevents the nanoion flux from crossing the cell membrane by preventing sodium channel activity, such as Ion flux. 'This compound will inhibit the ion flux through the voltage-dependent nanochannel. The compound is preferably a state of a nanochannel or a frequency dependent modifier having a low affinity for the ?/closed state and a high affinity for the deactivated state. , etc. Compounds may interact with overlapping positions in the lumen of the sodium-conducting pores of the channel' similar to those described for other state-dependent agents (Ce Shu, S. et al., the mind and the material... these things It may also interact with the location outside the lumen and have an ectopic effect on the pores of the nano-ion conduction channel. Any such result may ultimately be responsible for the overall therapeutic benefit provided by such compounds. 128409 -90- 200836743 Thus, the compounds of the present invention are nanochannel resistance _, I μu ❹ animals are preferably used in humans and other organisms for the treatment of diseases and symptoms, including the biological activity of the voltage-dependent sodium channel, or It can be improved by modulating the biological activity of a voltage-dependent sodium channel; human diseases and symptoms. As defined herein, a disease or symptom mediated by a sodium channel refers to the modulation of sodium in a mammal. Diseases or symptoms that are ameliorated during the passage, and include but are not limited to pain, central nervous system symptoms such as pain, sound, and bipolar diseases; cardiovascular symptoms, such as Arrhythmia, atrial fibrosis, ventricular fibrillation, and neurofibrillation; neuromuscular symptoms such as restless foot sign 'Yi and muscle itching or tetanus; resistance to stroke, nerve damage and multiple sclerosis neuroprotection; and channel disease, 嬖The present invention relates to a compound, a pharmaceutical composition, and a compound and a pharmaceutical composition, which are preferably a human, In humans, the method of treating sodium passages is widely used, and it is preferably a disease related to pain. The center: warp: such as pain, anxiety, inhibition and bipolar diseases; irregularity of cardiovascular disease, atrial fibrillation And ventricular fibrosis; nerve y two '譬 such as restless foot syndrome and muscle paralysis or tetanus; nerve damage and multiple sclerosis neuroprotection; and channel disease, L: species: pain and familial rectal pain symptoms 蔟In the form of a mammal, in need of such treatment, preferably a human blocker modulation (especially inhibition (4)., X to have a policy of Natuan, therefore, the present invention provides therapeutic lactation Or a method of protecting a mammal from 128409-91 - 200836743 for developing a disease (especially pain) mediated by sodium channels, comprising administering to a mammal in need, particularly a human, a therapeutically effective amount of a compound of the invention or comprising A pharmaceutical composition of a compound of the invention wherein the compound of the oxime is modulating the activity of one or more voltage-dependent sodium channels. The compounds of the invention are generally used in the medium, especially for inhibiting sodium channel ion flux, in the following The test assay described in the test paragraphs. Alternatively, the general value of the compound in the treatment of symptoms and disease can be broken in an industry standard animal model for the efficacy of a compounded compound in the treatment of pain. Animal models of human neuropathic pain symptoms It has been developed to cause reproducible sensory shortages (sensory abnormalities, hyperalgesia, and spontaneous pain) that can be assessed by sensory testing over a sustained period of time. By establishing the degree of sensory abnormalities and hyperalgesia caused by mechanical, chemical, and temperature conditions, several physiological and pathological symptoms found in humans can be modeled, allowing for the evaluation of medications. In the rat model of peripheral nerve injury, the ectopic activity in the injured nerve corresponds to signs of pain behavior. In these modes, the intravenous use of the sodium channel blocker and the local anesthetic lidocaine suppresses ectopic activity and reverses tactile sensation abnormalities at concentrations that do not affect general behavior and motor function (Mao, J). · With Chen, LL, (2000), 87: 7-17). In this type of rat model, the ratio of the effective dose to the body shape is converted into a dosage similar to that in humans (Tandian, D丄·与Br〇se, WG, ▲咖/^〇/〇砂( 1991), 74(5) · 949-951). Furthermore, Lidoderm® lidocaine, applied in the form of dermal patches, is currently an FDA-approved treatment for post-herpetic neuralgia (Devers, A· and Glaler, BS·, C/Plus. J. (2000) , 128409 -92- 200836743 16(3) : 205-8) The diseases or symptoms of the two-way media include pains associated with HIV, neuropathy caused by two or two treatments, three neuropathic pain, tongue and pharynx Nerve ^, ^ God _, obesity pain, thalamic injury, autoimmune diseases, asthma, drug addiction (such as opiates, benzodiazepine, amphetamine, alkali, alcohol, simmering) Alzheimer's disease, dementia, memory associated with aging, K_koff = 蔟, restenosis, urinary dysfunction, incontinence, Bajin's disease, cerebral blood, blood, neurosis, gastrointestinal disease, sputum Anemia, transplant rejection, heart failure, myocardial infarction, reperfusion injury, intermittent claudication, colic, expectoration, respiratory disease, brain or myocardial ischemia, long _QT sign fog, catechin Ventricular tachycardia, eye disease, paralysis , 痉f sex paraplegia, myopathy, myasthenia gravis, congenital myotonic sputum climbing, π-calcium periodic itching, hypokalemia periodic paralysis, baldness, anxiety, mental illness, mania , paranoia, seasonal affective disorder, fear disorder, confusing obsessive-compulsive disorder (〇CD), phobia, loneliness, cluster, Retts syndrome, collapse disorder, attention deficit disorder, aggressiveness, impulsive control disorder , thrombosis, pre-clamping, congestive heart failure ~ cessation, Freidrich's disorder, spinal cord and cerebellar disorders, spinal radiculopathy, systemic lupus erythematosus, granulomatous disease, olive body _ pons - cerebellum Atrophy, spinal cord and cerebellar disorders, incidental disorders, muscle fiber aggression, progressive pale globus atrophy, progressive supranuclear palsy and paralysis, traumatic brain injury, cerebral edema, hydrocephalus injury, spinal cord injury, neuropathy Disgusting, good #1, Prader-Willi syndrome, obesity, optic neuritis, cataract, 128409 -93- 200836743, synovial hemorrhage, hemorrhagic retinopathy, retinitis pigmentosa, acute K-moon lumen, speckle degeneration, retinal artery occlusion, chorea, Huntington's disease, cerebral edema, proctitis, post-herpetic neuralgia, normal pain, heat sensitivity, sarcoidosis, irritating bowel syndrome Peep, Durard syndrome, Podner's syndrome, Brugado syndrome, Liddle syndrome, Crohn's disease, multiple sclerosis, and pain associated with multiple sclerosis (MS), amyotrophic lateral sclerosis ( ALS), disseminated sclerosis, neuropathy in diabetic patients, peripheral neuropathy, charC0t_Marie dental syndrome, arthritis, rheumatoid arthritis, osteoarthritis, cartilage limestone, atherosclerosis'; paroxysmal muscle tone; i, muscle weakness syndrome, myotonia, myotonia dystrophy, muscular dystrophy, malignant hyperthermia, gallbladder fibrosis, pseudo aldosteronism, rhabdomyolysis, mental disorders, hypothyroidism, bipolar depression, anxiety, Schizophrenia, sodium channel toxin-related diseases, familial acral red pain, primary acral red pain, rectal pain, cancer

癲癇、部份與一般緊張發作、發熱發作、失神發作（癲癇小 發作）、肌陣攣發作、無緊張發作、陣攣發作、Lenn〇xGastaut、Epilepsy, partial and general tension, fever, absence of seizures (small seizures), myoclonic seizures, no seizures, clonic seizures, Lenn〇xGastaut,

West Syndome (嬰兒痙攣）、多重抵抗性發作、發作預防（抗 產生癲癇發作）、家族性地中海熱徵候簇、痛風、不安寧腳 部徵候箱、節律不齊、纖維肌痛、在因中風或神經損傷所 造成之絕血狀態下之神經保護、快速節律不齊、心房纖維 顫動與心室纖維顫動及因一般或局部麻醉劑。 、 上於本文中使用之”疼痛&quot;一詞係指所有種類之疼痛，且被 認為包括但不限於神經病原性疼痛、炎拇、皮 人丨王終痛、感受傷害 疼痛、自發性疼痛、神經性疼痛、口面疼 四尽痛、灼傷疼痛、 128409 -94- 200836743 :痛口部徵候簇、軀體疼痛、内臟疼痛、肌面疼痛、牙痛、 =疼=學療_、損傷疼痛、手術疼痛、手術後 &amp; 疼痛、分娩疼痛、反射交感性失養症、臂神經 :除、神經發生性膀胱、慢性疼痛、持續性疼痛、末梢 之疼痛、中樞媒介之疼痛、急性疼痛（例如肌骨盘手術 ^疼痛）、慢性頭痛、偏頭痛、家族性偏癱偏頭痛、與頭痛 關聯之症狀、竇房結頭痛、緊張頭痛、幻想肢疼痛、末 梢神經損傷、中風後疼痛、丘腦損傷、神經根病、HIV疼 痛疱療後疼痛、非心臟病胸痛、刺激性腸徵候襄及盘腸 病症和消化不良有關聯之疼痛，與麻醉藥上瘾戒除有關聯 之疼痛及其組合。 〜除了疼痛以夕卜’納通道阻斷劑具有臨床用途。癲癇與心 即律不齊經常為鈉通道阻斷劑之標的。得自動物模式之最 近註據’“鈉通道阻斷劑亦可在因中風或神經損傷所造 成之絕血狀態下及在患有多發性硬化之病患中用於神 ί 經保濩(Clare，JJ·等人，在m/逑之辜作户，與Anger, τ_等 k，在上文引述之著作中、。 本t明亦關於化合物，醫藥組合物，及使用此等化合物 與醫藥組合物以治療或預防疾病或症狀之方法，#如良性 攝護腺增生（BPH)、高膽固醇血症、癌症及搔癢病（癢症）。 乡良性攝護腺增生（BPH),亦稱為良性前列腺肥大，係為影 響老化男性之最常見疾病之一。BPH為進行性症狀’其特 Η為攝δ蔓腺組織之結狀腫大，造成尿道之阻塞。RPR之影 響可包括膀胱平滑肌之肥大、代償失調之膀胱、急性尿滯 128409 -95- 200836743 留及尿道感染之經增加發生率。 人顧t有高大眾健康衝擊，且為在年長男性中關於手術 ，丨入之最常見原因之一。 告 、n 原理，且ra 士告 進仃籌斌以闡明病因學與發病 、 $驗模式已被發展出。自發性動物模式伟被 限制於黑猩猩盥狗。* ,』t 八係被 ，、’在人類與狗中之BPH係共有許多共 特徵。在兩物種φ 年中BPH之發展係隨著已進展之年齡自然 地發生，且可藉由早期/前發身期閹割而被預防。對手術： 醫療替代方式係為治療卿及其影響所極為期望的。 在男f生與狗兩者中之攝護腺上皮增生係為雄激素敏 性，遭受伴隨著雄 〜 ^ 、 敦素丧失之退化，及當雄激素被取代時 復上皮曰生传自攝護腺之細胞已被註實會表現高含量 之私星選通鈉通道。免疫染色研究清楚地註實關於電屬選 k鈉k乙在攝濩腺組織中之註據咖肠如咖七伽 2〇〇5 ; 8(3) : 266-73) 〇 · 高膽固醇企症，意即經提高之血液膽固醇，在例如動脈 粥瘤硬化、冠狀動脈疾病'血脂肪過多、中風、胰島辛過 多、南血μ、肥胖、糖尿病、心血管疾病（cvd)、心肌絕血 及心臟病發作之發展上，係為經確立之危險因素。因此， =知在具有高膽固醇含量之個體中降低總血清膽固醇之含 量會降低此等疾病之風險。低密度脂蛋白膽固醇之降低特 別是在預防CVD上之-個必要步驟。雖然有多種高膽固醇 血症療法，但在此技藝領域中有持續需求且持續搜尋替代 療法。 本發明係提供化合物，其可作為抗高膽固醇血症劑使用， 128409 -96- 200836743 及其相關症狀。本發明化合物可以多種方式發生作用。雖 然不希望被束料任何料作㈣制，但該化合物可為酵 素醯基CoA :膽固醇酿基轉移酶（ACAT)之直接或間接抑制 劑，其會造成抑制膽固醇之醋化作用及㉟送越過腸壁。另 -種可能性可為本#明化合物可為在肝臟中膽固醇生物合 成之直接或間接抑制劑。可能情況是，本發明之一些化合 物可充作AC AT與膽固醇生物合成之直接或間接抑制劑兩 者0 搔疼病，-般稱為癢症，料常見皮膚症狀。雖然搔癢 病之確實原因係為複雜且缺乏瞭解，但長久以來係被認知 為與疼痛有交互作用。特定言之，咸認鈉通道多半沿著神 經轴索傳達或傳播癢症信號沿著皮膚。疼症脈衝之傳遞會 造成令人不舒服之感覺，其會誘發對㈣之需求或反射。 從神經生物學層次，一般認為有特定介體之共有複雜性、 相關神經元途徑及瘊症與疼痛之中央過程，且最近數據指West Syndome, multiple resistance seizures, seizure prevention (anti-seizures), familial Mediterranean heat syndrome, gout, restless foot stagnation box, arrhythmia, fibromyalgia, stroke or nerve Neuroprotection, rapid rhythm, atrial fibrillation and ventricular fibrillation in the blood vessels caused by injury, and general or local anesthetics. As used herein, the term "pain" refers to all types of pain and is considered to include, but is not limited to, neuropathic pain, inflammatory bowel, dermatitis, pain, spontaneous pain, Neuropathic pain, mouth pain, pain, burn pain, 128409 -94- 200836743: painful mouth syndrome, somatic pain, visceral pain, muscle pain, toothache, = pain = medical therapy _, injury pain, surgery Pain, post-operative &amp; pain, labor pain, reflex sympathetic dystrophy, brachial nerve: removal, neurogenic bladder, chronic pain, persistent pain, peripheral pain, central media pain, acute pain (eg musculoskeletal) Disk surgery ^ pain), chronic headache, migraine, familial hemiparesis, symptoms associated with headache, sinus node headache, nervous headache, fantasy limb pain, peripheral nerve injury, post-stroke pain, thalamic injury, radiculopathy, Pain associated with HIV pain, post-operative pain, non-cardiac chest pain, irritating bowel symptoms, and bowel disease and dyspepsia, associated with anesthesia addiction withdrawal Pain and its combination. ~ In addition to pain, Xi Bu 'na channel blocker has clinical use. Epilepsy and heart rhythm are often the target of sodium channel blockers. Recent injections of the animal model 'Sodium channel Blockers can also be used in patients with multiple sclerosis due to stroke or nerve damage and in patients with multiple sclerosis (Clare, JJ et al., at m/逑The author, and Anger, τ_ et al, in the work cited above, also relates to compounds, pharmaceutical compositions, and methods of using such compounds and pharmaceutical compositions for treating or preventing a disease or condition, #such as benign prostatic hyperplasia (BPH), hypercholesterolemia, cancer and scrapie (pruritus). Rural benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is the most common affecting aging men One of the diseases. BPH is a progressive symptom, which is characterized by a swell of the squamous gland tissue, causing obstruction of the urethra. The effects of RPR may include hypertrophy of the bladder smooth muscle, bladder with decompensation, and acute urinary stagnation 128409 - 95-200836743 Retention to urinary tract infections Increasing the incidence rate. People have a high public health impact, and it is one of the most common reasons for surgery in the elderly, the instinct, n principle, and ra Shizhao into the Qibin to clarify the etiology and The onset, the mode of detection has been developed. The spontaneous animal model is limited to chimpanzees and hyenas. * , 』t octagonal quilts, 'the BPH line in humans and dogs share many common features. In two species φ years The development of BPH in nature occurs naturally with the age of progression and can be prevented by castration during early/pre-existing period. For surgery: Medical alternatives are highly desirable for treatment and its effects. The prostate epithelial hyperplasia in both f and dog is androgen-sensitive, suffering from the degeneration of the male ~ ^, the loss of the dysentery, and when the androgen is replaced, the epithelial hyperplasia is transmitted from the prostate. Cells that have been labeled will exhibit high levels of private star-selected sodium channels. The immunostaining study clearly marked the injection of k-sodium k-B in the parotid gland tissue. According to the coffee gut, such as coffee, seven gag 2〇〇5; 8(3): 266-73) 〇· high cholesterol It means elevated blood cholesterol, such as atherosclerosis, coronary artery disease, 'blood fat, stroke, excessive islet, south blood μ, obesity, diabetes, cardiovascular disease (cvd), myocardial ischemia and heart The development of a disease is an established risk factor. Therefore, it is known that lowering the total serum cholesterol content in individuals with high cholesterol levels reduces the risk of such diseases. The reduction of low density lipoprotein cholesterol is a necessary step in the prevention of CVD. Although there are a variety of hypercholesterolemia therapies, there is a continuing need in this art field to continue searching for alternative therapies. The present invention provides a compound which can be used as an anti-hypercholesterolemia agent, 128409-96-200836743 and related symptoms. The compounds of the invention may act in a variety of ways. Although it is not desired to be made of any material (4), the compound may be a direct or indirect inhibitor of the enzyme sulfhydryl-based CoA: cholesterol-based transferase (ACAT), which causes the inhibition of cholesterol acetification and 35 delivery. Intestinal wall. Alternatively, the compound may be a direct or indirect inhibitor of cholesterol biosynthesis in the liver. It may be the case that some of the compounds of the present invention can be used as both direct or indirect inhibitors of AC AT and cholesterol biosynthesis, and are commonly referred to as itch, which is a common skin condition. Although the exact cause of scrapie disease is complex and lacks understanding, it has long been recognized as interacting with pain. In particular, the salty sodium channel mostly conveys or spreads the itching signal along the axonal line along the skin. The transmission of a painful pulse can cause an uncomfortable feeling that can induce a need or reflection on (4). From the level of neurobiology, it is generally believed that there is a common complexity of specific mediators, related neuronal pathways, and central processes of snoring and pain, and recent data refers to

:在疼痛與癢症-有關聯之末梢介體及/或受體之間有寬 廣重疊（Ik〇ma等人，胸_細·,讀__, 7: 535 547,藤）。 ，’疼痛與癢症在末梢神經系統與中樞神經系統中具 有神經it敏化作用之類似機制，但亦顯示情節差旦。 例如，#自抓癢之溫和疼痛刺激在消除疼症感覺上是有 :的。對照上而言，止痛劑譬如類阿片可產生嚴重搔癢病。 疼痛與疼症間之拮抗交互作用，可被利用於搔癢病療法 ，且目前研究係集中於未來止痛劑與止疼藥療法之共同 ^的之確認。 128409 -97- 200836743 甲，於口服劑量範 止痛作用。本發明 已证實本發明化合物在許多動物模式中 圍為1毫克/公斤至1〇〇毫克/公斤下具有止 化合物亦可用於治療搔癢病。 癢症或皮膚刺激之類型包括但不限於： a) 牛皮癖播癢病、由於血液透；J：斤所$6 、由於血液透析所致之癢症、瘧: There is a broad overlap between pain and itching-related terminal mediators and/or receptors (Ik〇ma et al., chest_fine, read __, 7: 535 547, vine). , 'Pain and itching has a similar mechanism of neuronal sensitization in the peripheral nervous system and the central nervous system, but it also shows that the plot is poor. For example, ##################################### In contrast, analgesics such as opioids can cause severe scrapie. Antagonistic interactions between pain and pain can be exploited for scrapie therapy, and current research is focused on the identification of future analgesics and painkillers. 128409 -97- 200836743 A, in the oral dose of analgesic effect. The present inventors have demonstrated that the compounds of the present invention have a stopping compound in the range of 1 mg/kg to 1 mg/kg in many animal modes and are also useful for the treatment of scrapie. Types of pruritus or skin irritation include, but are not limited to: a) psoriasis, itching, due to blood permeation; J: $6, pruritus due to hemodialysis, malaria

經病、精神原因素或其混合所造成之搔癢； b) 因過敏性反應、昆蟲咬傷、過敏性（例如乾焊皮_、 座瘡、《、牛皮癬）、炎性症狀或損傷所造成乾之；^; c) 與女陰前庭炎有關聯之癢症；及 d) 來自投予另一種治療劑之皮膚刺激或炎性作用，例 如抗生素、抗病毒劑及抗組織胺類。 本發明化合物亦可在哺乳動物較佳為人類中用於治療或 預防某些激素敏感性癌症，譬如攝護腺癌（腺癌）、乳癌、 卵巢癌、睪丸癌、甲狀腺腫瘤形成。電壓選通鈉通道已被 证貫係被表現在攝護腺與乳癌細胞中。初生15之向上 調節係在人類乳癌中發生，作為轉移性過程之一個完整部 伤，且可同時充作轉移性表現型與治療標的之新穎標記物 (C/kCa 騰 2005 年8月 1 日；11(15): 5381_9)。電壓選通鈉 通道α-亞單位，特別是NavL7之功能性表現，係伴隨著在攝 護腺癌（CaP)中，於活體外強轉移可能性。電壓選通鈉通道 〜亞單位免疫染色，使用對鈉通道^亞單位專一之抗體， 在攝護腺組織中係為顯著，且在CaP相對於非CaP病患中顯 著地較強 〇Pmstote Pmyi油t £)&amp;·，2005 ; 8(3) : 266-73)。 128409 -98- 200836743 本發明化合物亦可在侔左 思者BPH之哺乳動物中用於二 或預防病徵，嬖如作不职从&amp; &quot;療 。“_不限於急性尿滞留與尿道感染。 本發明化合物亦可Η Μ、/ β ,、 ;&gt;口療或預防某些内分泌平衡缺 或内分泌病，嬖如先天柯跃L ^ 天 。无天^腎上腺增生、甲狀腺機能亢進、 甲狀腺機能減退症、骨皙六 月貝&amp;鬆症 '骨軟化症、佝僂病、Cushing 氏徵候簇、Conn氏徵候燊、般m 、ra々 、、醃固酶過多症、性腺機能減退、 生殖腺官能過旺、不孕斥 卜子從、生育力及糖尿病。 rItching caused by disease, psychogenic factors or a mixture thereof; b) due to allergic reactions, insect bites, allergies (such as dry welding _, acne, "psoriasis"), inflammatory symptoms or injuries ;^; c) itch associated with vaginal vestibulitis; and d) skin irritation or inflammatory effects from administration of another therapeutic agent, such as antibiotics, antiviral agents, and antihistamines. The compounds of the invention may also be used in mammals, preferably humans, for the treatment or prevention of certain hormone-sensitive cancers, such as prostate cancer (adenocarcinoma), breast cancer, ovarian cancer, testicular cancer, thyroid neoplasia. Voltage-gated sodium channels have been shown to be present in prostate and breast cancer cells. The up-regulation of nascent 15 occurs in human breast cancer as a complete injury to the metastatic process and can simultaneously serve as a novel marker for metastatic phenotypes and therapeutic targets (C/kCa Teng August 1, 2005; 11(15): 5381_9). The voltage-gated sodium channel alpha-subunit, particularly the functional manifestation of NavL7, is associated with a strong metastatic potential in vitro in prostate cancer (CaP). Voltage-selective sodium channel ~ subunit immunostaining, using a specific antibody to the sodium channel ^ subunit, is prominent in the prostate tissue, and is significantly stronger in CaP than non-CaP patients 〇 Pmstote Pmyi oil t £) &·, 2005 ; 8(3) : 266-73). 128409-98-200836743 The compounds of the present invention can also be used in the prevention or treatment of symptoms in mammals of BPH, such as inadvertent &&quot; "_ is not limited to acute urinary retention and urinary tract infections. The compounds of the invention may also be Η Μ, / β , , ; &gt; oral therapy or prevention of certain endocrine balance or endocrine diseases, such as innate KE Yue L ^ days. ^Adrenal hyperplasia, hyperthyroidism, hypothyroidism, osteophyte June shell &amp; pine disease, osteomalacia, rickets, Cushing's syndrome, Conn's syndrome, general m, ra々, excessive carcinase Symptoms, hypogonadism, hypergonadism, infertility, fertility and diabetes.

本發明係容易地提供許？不同方式，以確認可作為治療 劑使用之鈉通道調·。納通道調·之確認可使用多種 活體外與活體内檢測評估，例如，度量電流、度量膜電位、 度量離子通量（例如鋼或脈鹽）、度量納濃度、度量第二信 使與轉錄含量，及使用例如電壓敏感性染料、放射性示縱 劑及貼片夾持電生理學。 一種此類擬案係涉及篩檢化學劑關於調制鈉通道活性之 能力，於是確認其作為調制劑。 於 Bean 等人，J·⑹而/ ρ_ζ·〇/〇处（1983), 83 : 613 642 與 Leuw% Μ.等人，价j· (2〇〇句，141⑴：47_54中所述之典型檢 測，係利用貼片夾持技術，以研究通道之行為。此種技術 係為熟諳此藝者所已知，且可使用現行技術，被發展至低 或中通過量檢測中，以評估化合物關於其調制鈉通道行為 之能力。 使用已知納通道毒素之競爭性結合檢測，譬如河豚毒素、 ①蝎毒素、烏頭素、BTX等，可適合用於確認對特定鈉通 道具有高選擇性之潛在治療劑。在此種結合檢測中利用 128409 -99- 200836743 BTX係為習知The present invention is easy to provide? Different ways to confirm the sodium channel modulation that can be used as a therapeutic agent. Nanochannel modulation can be assessed using a variety of in vitro and in vivo assays, such as measuring current, measuring membrane potential, measuring ion flux (eg, steel or vein salts), measuring nanoconcentration, measuring second messenger and transcription content, And clamping electrophysiology using, for example, voltage sensitive dyes, radioactive colorants, and patches. One such type of project involves the ability of a screening chemical to modulate the activity of a sodium channel, thus confirming it as a modulator. In Bean et al., J. (6) and / ρ_ζ·〇/〇 (1983), 83: 613 642 and Leuw% Μ. et al., valence j· (2 ,, 141(1): 47_54 Using patch-clamping techniques to study the behavior of the channel. This technique is known to those skilled in the art and can be developed into low or medium throughput assays using current techniques to evaluate compounds The ability to modulate the behavior of sodium channels. Competitive binding assays using known nanochannel toxins, such as tetrodotoxin, 1 scorpion toxin, aconitin, BTX, etc., are suitable for identifying potential therapeutic agents with high selectivity for specific sodium channels. The use of 128409-99-200836743 BTX system in this combination detection is a conventional

Med Chem, 且係被描述於McNeal，Ε·Τ·等人 (1985), 28(3) ： 381-8 ； M Creveling, C.R. # Λ ? 抑凑..#,瘦# # (C_ PM版)(1992): 25_37,大學出版社，— York 中。 此等檢測可在天然内源環境或在重組環境中，於表現吾 人感興趣通道之細胞或細胞或組織萃取物中進行。可使用 之檢測包括板檢測，其係度量經過替代標記物之流入 里，譬如14C-胍流入量，或測定細胞去極化作用，使用螢 光染料，譬如FRETS基礎者，及其他螢光檢測或放射性標 識結合檢測，採用放射性標識之烏頭素、Βτχ ' τ丁χ或§τχ。 更直接度量可以手動或自動化電生理學系統施行。脈流入 量檢測係更詳細地解釋於下文生物學檢測段落中。Med Chem, and is described in McNeal, Ε·Τ· et al. (1985), 28(3): 381-8; M Creveling, CR # Λ ? 抑 ...#,瘦# # (C_ PM版) (1992): 25_37, University Press, - York. Such assays can be performed in a natural endogenous environment or in a recombinant environment in cells or cell or tissue extracts that express channels of interest to us. Tests that can be used include plate detection, which measures the influx of surrogate markers, such as 14C-胍 influx, or cell depolarization, using fluorescent dyes, such as FRETS based, and other fluorescent detections or Radioactive labeling combined detection, using radioactive labeling of aconite, Βτχ 'τ丁χ or §τχ. More direct measurements can be performed manually or by automated electrophysiology systems. Pulse influx detection is explained in more detail in the biological test section below.

待測化合物之通過量為在選擇欲被使用篩選檢測上之一 項重要考量。在一些策略中，於數千種化合物中之數百種 欲被測試之情況中，一般不期望使用低通過量方式。但是， 在其他情況中，低通過量係令人滿意地鑒別有限數目化合 物間之重要差異。經常必須合併檢測類型，以確認特定通 道調制化合物。 使用貼片夾持技術之電生理學檢測，係被接受為詳細特 徵鑒定鈉通道化合物交互作用之金標準，且如如如等人， 在上文引述之著作中，氨M•荨人，在上文引述之著 所述者。有一種手動低通過量篩檢(LTS)方法，其每天 可比較2-10種化合物；一種關於自動化中等通過量篩檢 (MTS)之最近發展系統，在每天2〇_5〇個貼片（意即化合物） 128409 -100- 200836743 下；及一種來自分子裝置公司（Sunnyvale，CA)之技術，其允 許自動化高通過量篩檢（HTS)，在每天1000-3000個貼片（意即 化合物）下。 一種自動化貼片夾持系統係利用平面狀電極技術，以加 速藥物發現之速率。平面狀電極係能夠達成高電阻，細胞 貼附密封’接著為安定、低噪聲全細胞記錄，其可與習用 記錄比較。適當儀器為PatchXpress 7000A (Axon儀器公司，UnionThe throughput of the test compound is an important consideration in selecting the screening test to be used. In some strategies, in the case of hundreds of thousands of compounds to be tested, low throughput methods are generally not desired. However, in other cases, low throughput is a satisfactory identification of important differences between a limited number of compounds. It is often necessary to combine detection types to confirm specific channel modulation compounds. Electrophysiological testing using patch-clamping techniques is accepted as a gold standard for detailed characterization of sodium channel compound interactions, and as in, for example, in the work cited above, ammonia M•荨人, The above is quoted above. There is a manual low throughput screening (LTS) method that compares 2-10 compounds per day; a recently developed system for automated medium throughput screening (MTS) with 2〇5〇 patches per day ( Means compound) 128409-100-200836743; and a technology from the company of Sunnyvale (CA) that allows automated high throughput screening (HTS) with 1000-3000 patches per day (meaning compound) under. An automated patch-clamping system utilizes planar electrode technology to accelerate the rate of drug discovery. The planar electrode system is capable of achieving high electrical resistance, and the cell-attached seal is followed by a stable, low-noise whole-cell recording that can be compared to conventional records. The appropriate instrument is the PatchXpress 7000A (Axon Instruments, Union)

City，CA)。多種細胞系與培養技術，其包括黏連細胞以及自 發性地於懸浮液中生長之細胞，係被分等級，以提供密封 成功率與安定性。安定地表現高程度有關聯鈉離子通道之 不滅細胞（例如HEK與CHO)可被接合至高密度懸浮培養物 中0 可選擇其他檢測，其允許研究人員確認會阻斷特定通道 狀悲之化合物，譬如開啟狀態、關閉狀態或靜止狀態，或 其會阻斷從開啟至關閉、關閉至靜止或靜止至開啟之轉移。 熟諳此藝者一般係熟悉此種檢測。 結合檢測亦可採用，但是，此等只具有有限之功能性價 值與信息量。設計包括傳統放射性濾器為基礎之結合檢測， 或同焦點為基礎之螢光系統，可得自Evotec OAI公司集團 (Hamburg，Germany)，此兩者均為 HTS。 放射性通量檢測亦可使用。在此項檢測中，通道係以渥 特里丁（veratridine)或烏頭素刺激而開啟，並以毒素保 定化開啟狀態了，而通道阻斷劑係藉由其預防離子流入之 能力而被確認。此檢測可利用放射性22阐與14[c]脈鹽離 128409 -101 - 200836743 子作為示縱劑。在活細胞中之FlashPlate &amp; Cytostar-T板係避免 分離步驟且適合HTS。閃爍板技術亦已進展此方法至HTS適 合性。由於此檢測之功能性方面，故信息量係合理地良好。 又另一種格式係使用FLIPR系統膜電位套組（HTS)度量膜 電位之再分佈，其可得自分子動態學（Molecular Dynamics) (Amersham Biosciences之一個部門，Piscataway，NJ)。此方法係被 限制於減緩膜電位改變。一些問題可由於化合物之螢光背 景所造成。待測化合物亦可直接影響細胞膜之流動性，且 會導致增加胞内染料濃度。又由於檢測之功能性方面，故 信息量係合理地良好。 可使用鈉染料以度量鈉離子流入經過通道之速率或量。 此類型之檢測係提供關於潛在通道阻斷劑之極高信息量。 此檢測為功能性，且直接度量Na+流入量。CoroNa紅色、SBH 及/或鈉綠色（Molecular Probes公司，Eugene OR)可用以度量Na 流入量；全部均為Na回應性染料。其可與FLIPR儀器合併使 用。此等染料於篩檢中之利用未曾於先前被描述於文獻 中。鈣染料在此格式中亦可具有潛力。 在另一種檢測中，係使用FRET為基礎之電壓感測器以度 量待測化合物直接阻斷Na流入之能力。市購可得之HTS系 統包括VIPRT MII FRET系統（Aurora生物科技公司，San Diego, CA，Vertex醫藥公司之一個部門），其可搭配FRET染料使用， 其亦可得自Aurora生物科技。此項檢測係度量對電壓改變之 亞秒回應。無需通道功能之改變劑。此檢測係度量去極化 作用與過度極化，且提供比例計輸出，以供定量。此項檢 128409 -102- 200836743 測之稍微較不昂貴MTS變型係採用FLEXstati0nTM(分子妒置 公司），並搭配得自Aurora生物科技之FRET染料。測試本文 中所揭示化合物之其他方法，亦為熟諳此藝者所立即已知 且可採用。 此等結果係提供分析待測化合物與鈉通道間之結構-活 I4生關係（SAR)之基礎。於待測化合物核心結構上之某此取代 基，有助於提供更有效抑制化合物。SAR分析為熟諳此藝 者目前可採用工具之一，以確認本發明化合物之較佳具體 實施例作為治療劑使用。 然後，將經如此確認之調制劑在多種活體内模式中測 試，以測定其是否會減輕疼痛，尤其是慢性疼痛或其他症 狀，譬如節律不齊與癲癇、良性攝護腺增生（BpH)、高膽固 醇血症、癌症及搔癢病（癢症），伴隨著最少不利事件。下 文在生物學檢測段落中所述之檢測，可使用於評估本發明 化合物之生物學活性。 典型上，本發明之成功治療劑將符合一部份或全部下列 標準。口服使用性應在於或高於2〇%。動物模式功效係低 於約ο·ι微克/公斤至約100毫克/公斤體重，而標的人類劑量 係在0.1微克/公斤至約100毫克/公斤體重之間，惟在此範圍 外之劑量為可接受的（”毫克/公斤”係意謂被投予病患每千 克身體質ΐ之化合物毫克數）。治療指數（或中毒量對治療 劑量之比例）應大於100。功效（當藉由冗⑼值表示時）應低於 10 //Μ，較佳係低於丨_，而最佳係低於5〇ηΜ。iC5〇(&quot;抑制 濃度·50〇/〇”）為在本發明之一項檢測中，於特定時期内，為達 128409 -103- 200836743 成離子通量經過鈉通道之50%抑制作用所需要化合物量之 一種度量。在脈流入量檢測中，本發明化合物已註實1C, 範圍係從低於一毫微莫耳濃度至低於10微莫耳濃度。 在本發明之一種替代用途中，本發明化合物可用於活體 外或活體内研究，作為舉例劑，供比較目的，以發現其他 亦可用於治療或保護以防止本文中所揭示各種疾病之化合 物0 本發明之另一方面係關於在生物試樣或哺乳動物（較佳 為人類）中抑制NavU，Nav1.2, Navl.3, NavU，Navl 5, NavU， Μν1·7，Ναν1.84Ναν1.9活性，此方法包括對該哺乳動物，較 佳為人類，投予式〗化合物或包含該化合物之組合物或使 該生物試樣與其接觸。於本文中使用之&quot;生物試樣&quot;一詞， 係包括但不限於細胞培養物或其萃取物&quot;寻自哺乳動物或 其萃取物之活體組織檢查物質；及血液、唾液、尿液、糞 便、精液、眼淚或其他體液或其萃取物。 \ 生物試樣中 NavU，Navl.2, NavU，NavU，City, CA). A variety of cell lines and culture techniques, including adherent cells and cells that grow spontaneously in suspension, are graded to provide seal success and stability. Intacting cells with high levels of associated sodium channels (eg, HEK and CHO) can be ligated into high-density suspension cultures. 0 Other assays can be selected that allow the investigator to confirm that specific channel-like compounds are blocked, such as Turned on, off, or quiescent, or it blocks the transition from on to off, off to standstill or still to on. Those skilled in the art are generally familiar with such tests. Combined detection can also be used, but these have only a limited amount of functional value and information. The design includes a combination of traditional radioactive filter-based detection, or a focus-based fluorescent system, available from the Evotec OAI Group of Companies (Hamburg, Germany), both of which are HTS. Radioactive flux detection can also be used. In this assay, the channel was activated by stimulation with veratridine or aconitin and was inactivated with toxins, and channel blockers were identified by their ability to prevent ion influx. This test utilizes radioactivity 22 to illustrate 14[c] vein salt as 128409 -101 - 200836743 as an extender. The FlashPlate &amp; Cytostar-T plate in live cells avoids the separation step and is suitable for HTS. The scintillation panel technology has also advanced this approach to HTS suitability. Due to the functional aspects of this test, the amount of information is reasonably good. Yet another format uses the FLIPR System Membrane Potential Kit (HTS) to measure the redistribution of membrane potential, which is available from Molecular Dynamics (a division of Amersham Biosciences, Piscataway, NJ). This method is limited to slowing membrane potential changes. Some problems can be caused by the fluorescent background of the compound. The test compound can also directly affect the fluidity of the cell membrane and lead to an increase in intracellular dye concentration. Due to the functional aspects of the detection, the amount of information is reasonably good. Sodium dyes can be used to measure the rate or amount of sodium ions flowing through the channel. This type of test provides an extremely high amount of information about potential channel blockers. This test is functional and directly measures Na+ influx. CoroNa red, SBH and/or sodium green (Molecular Probes, Eugene OR) can be used to measure Na influx; all are Na responsive dyes. It can be combined with FLIPR instruments. The use of such dyes in screening has not been previously described in the literature. Calcium dyes also have potential in this format. In another test, a FRET-based voltage sensor is used to measure the ability of the test compound to directly block Na influx. Commercially available HTS systems include the VIPRT MII FRET system (Aurora Biotech, Inc., San Diego, CA, a division of Vertex Pharmaceuticals), which can be used with FRET dyes, which are also available from Aurora Biotechnology. This test measures the sub-second response to voltage changes. No need to change the channel function. This test measures depolarization and hyperpolarization and provides a proportional output for quantification. This inspection, 128409 -102-200836743, is a slightly less expensive MTS variant using FLEXstati0nTM (Molecular Devices) with FRET dyes from Aurora Biotech. Other methods of testing the compounds disclosed herein are also known and available to those skilled in the art. These results provide the basis for analyzing the structure-live I4 relationship (SAR) between the test compound and the sodium channel. One such substituent on the core structure of the compound to be tested helps to provide a more effective inhibitory compound. SAR analysis is currently one of the tools available to those skilled in the art to confirm that preferred embodiments of the compounds of the invention are useful as therapeutic agents. The thus-confirmed modulator is then tested in a variety of in vivo modes to determine if it will reduce pain, especially chronic pain or other symptoms such as irregularities and epilepsy, benign prostatic hyperplasia (BpH), high Cholesterolemia, cancer, and scrapie (itch) are accompanied by the least adverse events. The assays described below in the biological assay section can be used to assess the biological activity of the compounds of the invention. Typically, the successful therapeutic agents of the present invention will meet some or all of the following criteria. Oral use should be at or above 2%. The animal model efficacy is less than about οι/g to about 100 mg/kg body weight, and the standard human dose is between 0.1 microgram/kg to about 100 mg/kg body weight, except for doses outside this range. Accepted ("mg/kg" means the number of milligrams of compound administered to the patient per kilogram of body mass). The therapeutic index (or the ratio of the amount of poisoning to the therapeutic dose) should be greater than 100. Efficacy (when expressed as a verbose (9) value) should be less than 10 // Μ, preferably less than 丨 _, and the best is less than 5 〇 Μ. iC5〇(&quot;inhibition concentration·50〇/〇) is required for a 50% inhibition of the ion flux through the sodium channel in a test of the present invention for a specific period of time: 128409 -103-200836743 A measure of the amount of a compound. In the pulse influx assay, the compound of the invention has been labeled 1C, ranging from below a nanomole concentration to below 10 micromolar. In an alternative use of the invention, The compounds of the invention may be used in in vitro or in vivo studies, as an exemplifying agent, for comparison purposes, to discover other compounds which may also be used in the treatment or protection against the various diseases disclosed herein. Inhibiting NavU, Nav1.2, Navl.3, NavU, Navl 5, NavU, Μν1·7, Ναν1.84Ναν1.9 activity in a sample or mammal (preferably human), the method comprising the mammal, Preferably, the human compound, the composition of the compound or the composition comprising the compound or the biological sample is contacted therewith. The term "biological sample" as used herein includes, but is not limited to, cell culture or Extract Take &quot; biopsy substances from mammals or their extracts; and blood, saliva, urine, feces, semen, tears or other body fluids or their extracts. \ Biological sample NavU, Navl.2, NavU, NavU,

Navl_7, NavU或NavL9活性之抑制，可用於熟諸此藝者已知 之多種㈣。此種目的之實例包括但不限於納離子通道在 生物學與病理學現象中之研究；及新_離子通道抑制劑 之比較評估。 如上文在發明内容中所提出之本 S H X月化合物，為其立體 異構物、對掌異構物、互變異構物或 义具此合物，或其藥學 上可接嗳之鹽、溶劑合物或前體藥物， M w 及/或本文中所述之 面樂組合物，其包含藥學上可接受 又义賦形劑，與一或多種 128409 -104- 200836743 如上文在發明内容中所揾 ^ 杈出之本發明化合物，為其立體里 構物、對掌異構物、互變里 &quot; 文異構物或其混合物，或其藥 可接受之鹽、溶劑合物或前_ …、 j體樂物，可用於製備藥劑，以 在咕乳動物中治療鈉通道所媒介之疾病或症狀。 本發明之醫藥組合物與投藥 本發明亦關於含有本文中所4 — 中所揭不本發明化合物之醫藥組 合物。於一項具體實施例中， 本t明係關於一種醫藥組合 ，山本發明化合物’在藥學上可接受之賦形劑、載 :丨或稀釋劑中’而當被投予動物，較佳為哺乳動物，最佳 為人類時，其量可有效調制， # ^為抑制離子通量經過電 =賴性納通道，以治療_道所媒介之疾病，譬如疼痛。 /發明化合物或其藥學上可接受之鹽，呈純形式或 當醫藥組合物中之投藥，可經由 ^ 」、、二由充作類似利用性之藥 任何所接受投藥模式進行。本發明之醫藥組合物可經由將 :明化合物與適當藥學上可接受之載劑、稀釋劑或賦形 K开而製成，且可被調配成製劑，呈固體、半固 體或氣體形式’譬如片劑、膠囊、粉末、顆粒、軟膏二 液 '栓劑、注射劑、吸藥、凝膠、微球體及氣溶膠。二 此種醫藥組合物之典型途徑包括但不限於口服、局部^ 皮、吸入、非經腸、舌下、直腸、陰道及鼻内。於本文 使用之非經腸一詞，包括皮下注射、 静脈内、肌内、胸骨 内注射或灌注技術。本發明之醫藥組合物係經調配， :寺其中所包含之活性成份在對病患投予該組合物時 句了利用。被投予患者或病患之組合物係採取一或多種劑 128409 -105- 200836743 量單位形式，其中例如片劑可為單一劑量單位，而呈氣容 膠形式之本發明化合物之容器可容納多個劑量單位。製備 此種劑型之實際方法係為熟諸此藝者所已知或將為其㈣ 瞭，例如’茶閱農藥存學與實濟，第2〇版师脇响a製 與科學學院，鳩）。欲被投予之組合物無論㈣將含有治療 上有效量之本發明化合物或其藥學上可接受之鹽，以根據 本發明之陳述内容治疼五λ # 奋/α黡Q人感興趣之疾病或症狀。 可用於此處之醫藥組合物亦含有藥學上可接受之載劑， 包括任何適當稀釋劑或賦形劑，其包含任何本身不會引致 產生對接受組合物之個辦古堂 個體有害抗體之藥劑，且其可投予而 無不當毒性。藥學上可技為+ 1十丨人 了接又之載劑包括但不限於液體，壁 二二鹽水、甘油及乙醇等。藥學上可接受之载劑、稀釋 劑及其他賦形劑之奋公y入父么口 科番…山 現於職1NGT〇N氏醫藥 科學（Mack出版公司，NJ•，現行版本）中。 本發明之醫藥組合物可呈固體或液體形式。於一方面， :劑為微粒子，以致組合物係例如呈片劑或粉末形式。載 劑可為液體，JL中也人必炎 -中，，“物為例如口服糖漿、可注射液體或 了用於例如吸入投藥之氣溶膠。 ^开欲Γ服投藥時’醫藥組合物較佳係呈無論是固體或 /夜體^式，甘φ主丨&gt; I、體、半液體、懸浮液及凝膠形式係被 3 文被視為無論是固體或液體之形式中 作為供口服投藥用之固體組合物，醫荜二:。 成粉末、顆粒、壓縮片劑、丸劑、…口二勿可被調配 ^ϋ香糖、扁片或 ㈣物典型上含有一或多種惰性稀 128409 200836743 玉米；殿粉等；潤 譬如膠態二氧化 譬如薄荷、柳酸 釋劑或可食用載劑。此外，一或多種下列物質可以存在. 黏合劑’譬如幾甲基纖維素、乙基纖維素、微晶性纖唯素 西黃箸樹膠或明膠’·賦形劑’譬如殺粉、乳糖或糊 解劑，譬如海藻酸、海藻酸鈉、prim()gei 滑劑，譬如硬脂酸鎂或Ster〇tex ;助流劑 矽；增甜劑，譬如蔗糖或糖精；矯味劑 甲酯或橘子矮味劑；及著色劑。 當醫藥組合物係呈膠嚢之梆々 y , 壬胗襄之形式，例如明膠膠囊時， 上述類型之物質以外’其可含有液體載劑，譬如聚乙：r 或油。 予 醫藥組合物可呈液體之形式，例如馳劑、糖聚、 乳化液或懸浮液。此液體可供口服投藥，或藉由注射傳輸： 作為兩種實例。當欲供口服投藥時，較佳組合 明化合物以外’含有—或多種増甜劑、防腐劑、染料/著I 劑及橋味增強劑。在意欲藉由注射投予之組合物中， 多種界面活性劑、防腐劑、濁濕劑、分散劑、、缓 衝劑、安定劑及等滲劑可被加入。 鲛 :發明之液體醫藥組合物’無論其係為溶 =類似形式，可包含-或多種下列佐劑：無菌稀釋劑 言如注射用水’鹽水溶液’較佳為 、、态，楚焱备儿“ 民皿不，林袼氏溶 :專㈣化納，不揮發油’譬如合成單或二酸甘油酿， :可充作 &gt;谷劑或懸浮媒質，I乙二醇、甘油、丙二醇或立 溶劑；抗細菌劑’譬如罕醇或對經基苯甲酸甲賴；二： 化劑’譬如抗壞灰酸或亞硫酸氫鈉；螯合劑，譬：乙：: 128409 -107- 200836743 四S曰齩’緩衝劑’譬如醋酸鹽、擰檬酸鹽 整渗透性之作用劑，譬如氯化納或右旋糖。非經㈣= 被裝在由玻璃或塑可 ㈣旦A _成之安瓶瓶、用後即棄注射器或多 重知丨里小玻瓶中。生理食醆 合物較佳為無菌。4為g佐劑。可注射醫藥組 物廡人：：疋1卜經腸或口服投藥用之本發明液體醫藥組合 -數Ϊ之本發明化合物’以致將獲得適當劑量。 典型上，此量係為至少嶋之本發明化合物在組合物中。 當欲供口服投藥時，此量可在組合物重量之01與約概之 間改變。較佳口服醫藥組合物係含有約4%與約50%間之本 ㈣化合物°㈣本發明之較佳醫藥組合物與製劑係被f 成，以致在本發明稀釋之前，非經腸㈣單位含有請至10 重量％間之化合物。 本發明之醫藥組合物可能欲供局部投藥，於此種情況中， 载劑可適當地包括溶液、乳化液、軟膏或凝膠基料。例如， 此基料可包括一或多種下列物質：石蠟油、羊毛脂聚乙 二醇、蜂躐、礦油，稀釋劑，譬如水與醇，及乳化劑盘安 定劑。增稠劑可存在於供局部投藥之醫藥組合物中。若欲 供經皮投樂，則組合物可包括經皮貼藥或離子電渗裝置。 局部配方可含有本發明化合物之濃度為約(U至約· w/v (每單位體積之重量）。 本發明之醫藥組合物可能欲供直腸投藥，呈例如栓劑形 式，其將在直腸中溶解，並釋出藥物。供直腸投藥之組合 物可含有油質基料，作為適當無刺激性賦形劑。此種基料 128409 -108- 200836743 係包括但不限於羊毛脂、可可豆脂及聚乙二醇。 本表明之醫藥組合物可包含各種物質，其係修改固體或 液體劑量單位之物理形式。例如，此組合物可包含會形成 塗層外殼環繞活性成份之物質。形成塗層外殼之物質典型 上為惰性’且可選自例如糖、蟲膠及其他腸溶性塗覆劑。 或者，活性成份可被裝入明膠膠囊中。 呈固體或液體形式之本發明醫藥組合物可包含一種會結 合至本發明化合物’且藉以幫助化合物傳輸之作用劑：可 以此能力發生作用之適當作用劑包括單株或多株抗體、蛋 白質或微脂粒。 本發明之醫藥組合物可包含劑量單位，其可以氣溶膝投 谷谬-詞係用以表示多種系統，範圍從膠態性質者 ^ 《之系統。傳輸可藉由液化或壓縮氣體，或 错由會分配活性成份之適者 通田果糸統。本發明化合物之氣溶 ;了 早相、兩相或二相 溶膠之傳傳輸活性成份。氣 專輸包括必要之容器、促動器、活門、亞容器等， ^ 起構成套件。熟諳此藝者益需1 佳氣溶膠。 4 —過度實驗即可決定較 本lx明之醫藥組合物可藉 製成。例如，咅❹知之操作法 本發明化合物盥益_桌、、、口物，可猎由將 加界面活性:一、館水合併以形成溶液而製成。可添 Μ，以幫助均勻溶液或懸 性劑為以非丘價方4m 夜之形成。界面活 -物，k 式與本發明化合物交互作用，以促進化 °物在水溶液傳輸系統中之溶解或均㈣浮之化合物。 128409 200836743 本發明化合物或其藥學上可接受之鹽係以治療上有效量 投予，其將依多種因素而改變，包括所採用特定化合物之 活性；化合物之代謝安定性與作用長度；病患之年齡、體 重、一般健康狀態、性別及飲食；投藥模式與時間；排泄 速率；藥物組合；特定病症或症狀之嚴重性；及接受治療 之病患。一般而言，治療上有效之曰服劑量為（對70公斤哺 乳動物而言）約〇·〇〇1毫克/公斤（意即〇·〇7毫克）至約100毫克 /公斤（意即7·0克）；治療上有效劑量較佳為（對70公斤哺乳 動物而言）約0.01毫克/公斤（意即0.7毫克）至約50毫克/公斤 (意即3.5克）；治療上有效劑量更佳為（對70公斤哺乳動物而 言）約1毫克/公斤（意即70毫克）至約25毫克/公斤（意即1.75 克）。 本文中所提供之有效劑量範圍並非意欲成為限制，而係 代表較佳劑量範圍。但是，最佳劑量係針對個別病患作修 訂，其係為熟諳有關聯技藝者所明瞭且可測定（參閱，例如 Berkow 等人編著，Merck 手冊，第 16 版，Merck 公司，Rahway，N.J.， 1992 ; Goodmanetna編著，Goodman與Cilman氏治療學之藥理學 基礎，第 10 版，Pergamon 出版公司，Elmsford，N.Y.，（2001) ; Avery 氏藥物治療：臨床藥理學與治療學之原理與實務，第3版， ADIS 出版公司，Williams 與 Wilkins，Baltimore，MD. (1987)，Ebadi 藥 理學，Little，Brown 公司，Boston (1985) ; Osolci al.編著，Remington 氏醫藥科學，第18版，Mack出版公司（Easton，PA) (199〇); Katzung，基礎與臨床藥理學，Appleton 與 Lange，Norwalk，CT (1992))。 128409 -110- 200836743 宁於各治療所需要 曰 ，蜊里虱以罝—w $，在當天期間内（若需要）投予。一般而言，、、Λ 背 少劑量起始，其係低於此化合物之最適宜齊^量:=以， 由小増量’增加此劑量’直到在此等狀況下達到：:’错 果為止。診斷醫藥化合物或組合物可單獨或搭二= 理學疾病或針對該病理學疾病其他病徵之 /丙 吱醫Μ π ;丄々 -、他0斷劑及/ 或…予。本發明化合物及/或组合物投藥之 為任何脊椎動物，譬如哺乳動物。 受者為靈長類動物目（包括人類、無尾猿;;物子中1佳接 動物目（包括馬、山羊、母牛、缚羊、=)、偶蹄類 ^ ^ ^ ^ ^ 豬）齧齒動物目（包 ，、大白氣、兔子及大頻鼠)及食肉類動物目(包括r :、狗)之哺乳動物。在鳥類中，較佳接受者為火雞' : 同目之其他成員。最佳接受者為人類。 對局部應用而言，較佳係投 组合物至尸的^ w 予有心之根據本發明醫藥 … 例如皮膚表面、黏膜等，其係鄰近欲 約讀⑴毫克至約卫克之本發=人^之範圍為每次塗敷 而定，無論其用途為診斷 依欲被治療之面積 、方或&gt;α療，病徵嚴重性及所 採用局部媒劑之性質。較佳 膏基料係使用約卿至㈣^^為以’其令每㈣ 祐抑m…克性成份。醫藥組合物可 =二皮組合物或經皮傳輪裝置(&quot;貼藥&quot;)。此 著ΓΙ二/性化合物儲器、控制膜、内襯及接觸黏 本二化:：可用以提供連續搏動，或依要求傳輸 本發明化合物，按需要而定。 128409 -111 - 200836743 本發明之纟且人札《_ρ Μ — 、、口勿可猎由採用此項技藝中已知之程序進行 調配，以在斜、由&amp; Μ 、， …心扠樂後，提供活性成份之快速、持續戋 延f釋=。受控釋出藥物傳輸系統包括滲透泵系統與溶解 糸統’合有聚合體塗覆之儲器或藥物-聚合體基質配方。受 控釋出系統之實例係示於美國專利讽770與4,风奶中， 在Kuzma等人，昼域沒靡鮮22⑹：543-551 (例7)中，其 全部均併於本文供參考。 ” a本發明之組合物亦可經過鼻内藥物傳輸系統傳輸，供局The inhibition of Navl_7, NavU or NavL9 activity can be used for a variety of (4) known to those skilled in the art. Examples of such purposes include, but are not limited to, studies of nanochannels in biological and pathological phenomena; and comparative evaluation of new ion channel inhibitors. The present SHX compound as set forth in the above summary is a stereoisomer, a palmomer, a tautomer or a compound thereof, or a pharmaceutically acceptable salt thereof or a solvent thereof. Or a prodrug, M w and/or a noodle composition as described herein, comprising a pharmaceutically acceptable excipient, with one or more of 128409-104-200836743 as set forth above in the Summary of the Invention ^ The compound of the present invention, which is a stereoscopic structure, a palmomer, a tautomer, or a mixture thereof, or a pharmaceutically acceptable salt, solvate or precursor thereof, A body fungus that can be used to prepare a medicament for treating a disease or condition mediated by a sodium channel in a suckling animal. Pharmaceutical Compositions and Administration of the Invention The present invention also relates to pharmaceutical compositions containing the compounds of the invention as disclosed herein. In one embodiment, the present invention relates to a pharmaceutical combination, wherein the compound of the invention is in a pharmaceutically acceptable excipient, in a hydrazine or a diluent, and is administered to an animal, preferably breast-feeding. Animals, when optimally human, can be effectively modulated by the amount of #^ to suppress the ion flux through the electricity-reducing nanochannel to treat diseases such as pain. The compound of the invention or a pharmaceutically acceptable salt thereof, administered in pure form or in a pharmaceutical composition, can be administered by any of the accepted modes of administration as a drug of similar utility. The pharmaceutical compositions of the present invention can be prepared by dissolving the compound with a suitable pharmaceutically acceptable carrier, diluent or excipient K, and can be formulated into a solid, semi-solid or gaseous form, such as Tablets, capsules, powders, granules, ointments, two suppositories, suppositories, injections, drugs, gels, microspheres and aerosols. 2. Typical routes for such pharmaceutical compositions include, but are not limited to, oral, topical, inhalation, parenteral, sublingual, rectal, vaginal and intranasal. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or perfusion techniques. The pharmaceutical composition of the present invention is formulated, and the active ingredient contained in the temple is utilized when administering the composition to a patient. The composition to be administered to a patient or a patient is in the form of one or more doses of 128409 - 105 - 200836743, wherein, for example, the tablet may be a single dosage unit, and the container of the compound of the invention in the form of a gutta-percha can accommodate more Dosage unit. The actual method for preparing such a dosage form is known to those skilled in the art or will be (4), for example, 'tea reading pesticides and livelihood, the second edition of the division of the syllabus and science, 鸠) . The composition to be administered, whether or not (4) will contain a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof, in order to treat a disease of interest to a person according to the present invention. Or symptoms. The pharmaceutical compositions useful herein also contain a pharmaceutically acceptable carrier, including any suitable diluent or excipient, which comprises any agent which does not itself cause the production of harmful antibodies to the individual receiving the composition. And it can be administered without undue toxicity. The pharmacy is +1 丨人. The carrier is included, but not limited to liquid, wall brine, glycerin and ethanol. Pharmacologically acceptable carriers, diluents and other excipients are used in the company's 1NGT〇N medical science (Mack Publishing Company, NJ•, current version). The pharmaceutical compositions of the invention may be in solid or liquid form. In one aspect, the agent is a microparticle such that the composition is, for example, in the form of a tablet or powder. The carrier may be a liquid, and the JL may also be inflammatory-in-progressive, "the substance is, for example, an oral syrup, an injectable liquid or an aerosol for administration, for example, by inhalation. Whether it is a solid or a noctural formula, the main genus &gt; I, body, semi-liquid, suspension and gel form are considered to be administered orally in solid or liquid form. The solid composition used, the doctor's two: into powder, granules, compressed tablets, pills, ... can not be formulated ^ ϋ 、 、, flat sheet or (four) typically contains one or more inert dilute 128409 200836743 corn ; Palace powder; etc.; such as colloidal cerium oxide such as peppermint, salicylic acid release agent or edible carrier. In addition, one or more of the following substances may be present. Binders such as methine cellulose, ethyl cellulose, micro Crystalline cellulose, jaundice gum or gelatin '·excipients' such as powder, lactose or a gelatin, such as alginic acid, sodium alginate, prim () gei slip agent, such as magnesium stearate or Ster Tex; glidant 矽; sweeteners, such as sucrose or saccharin; flavoring agent a methyl ester or an orange dwarf; and a coloring agent. When the pharmaceutical composition is in the form of a capsule, such as a gelatin capsule, other than the above-mentioned substances, it may contain a liquid carrier, such as Polyethylene: r or oil. The pharmaceutical composition may be in the form of a liquid, such as a granule, a sugar concentrate, an emulsion or a suspension. This liquid may be administered orally or by injection: as two examples. For oral administration, it is preferred to combine a compound containing or a plurality of sweeteners, preservatives, dyes/I agents, and bridge taste enhancers. In the composition intended to be administered by injection, a plurality of surfactants Preservatives, wetting agents, dispersing agents, buffering agents, stabilizers and isotonic agents may be added. 鲛: The liquid pharmaceutical composition of the invention 'whether it is a solution = a similar form, may contain - or a plurality of the following Adjuvant: Sterile diluent, such as water for injection, 'salt aqueous solution' is preferred, state, Chu 焱 prepare children "Xi Dian not, Lin Biao Shi: special (four) sodium, non-volatile oil, such as synthetic mono- or diglyceride Stuffed: can be used as a &gt; Floating medium, I glycol, glycerin, propylene glycol or stereosolvent; antibacterial agent '譬 罕 罕 或 或 对 对 或 对 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;譬: B:: 128409 -107- 200836743 Four S曰齩 'buffering agent' such as acetate, citrate osmotic agent, such as sodium chloride or dextrose. Non-menstrual (4) = is contained in a glass bottle or a plastic bottle (four) Dan A _ into the bottle, disposable syringe or more in the small glass bottle. The physiological food composition is preferably sterile. 4 is g adjuvant. Injectable Pharmaceutical Groups: The liquid pharmaceutical combination of the present invention, which is administered orally or orally, is administered to a compound of the present invention so that an appropriate dose will be obtained. Typically, this amount is at least the compound of the invention in the composition. When intended for oral administration, this amount can vary between 01 and about the weight of the composition. Preferably, the oral pharmaceutical composition contains between about 4% and about 50% of the compound (IV). (IV) The preferred pharmaceutical compositions and formulations of the present invention are formulated such that the parenteral (four) unit is included prior to dilution of the present invention. Please go to 10% by weight of the compound. The pharmaceutical compositions of the present invention may be intended for topical administration, in which case the carrier may suitably comprise a solution, emulsion, ointment or gel base. For example, the base may comprise one or more of the following: paraffinic oil, lanolin polyethylene glycol, bee mites, mineral oil, diluents such as water and alcohol, and emulsifier tray stabilizers. Thickeners may be present in the pharmaceutical compositions for topical administration. If percutaneous injection is desired, the composition may include a transdermal patch or an iontophoresis device. The topical formulation may contain a concentration of the compound of the invention of about (U to about w/v (weight per unit volume). The pharmaceutical composition of the invention may be intended for rectal administration, for example in the form of a suppository, which will dissolve in the rectum And releasing the drug. The composition for rectal administration may contain an oleaginous base as a suitable non-irritating excipient. Such bases 128409-108-200836743 include but are not limited to lanolin, cocoa butter and poly Ethylene glycol. The pharmaceutical compositions of the present invention may comprise a variety of materials which modify the physical form of the solid or liquid dosage unit. For example, the composition may comprise a material which will form a coating shell surrounding the active ingredient. The substance is typically inert and may be selected, for example, from sugars, shellac and other enteric coating agents. Alternatively, the active ingredient may be enclosed in a gelatin capsule. The pharmaceutical composition of the invention in solid or liquid form may comprise a An agent that binds to a compound of the invention' and thereby aids in the delivery of the compound: suitable agents that can function with this ability include single or multiple antibodies, proteins or The medicinal composition of the present invention may comprise a dosage unit which can be used to represent a variety of systems, such as a system of colloidal properties, which can be transported by liquefaction or compression. Gas, or the wrong one that will distribute the active ingredient. The compound of the present invention is gas-soluble; the early phase, two-phase or two-phase sol transports the active ingredient. The gas-only transmission includes the necessary container and actuation. , the valve, the sub-container, etc., to form a kit. Those who are familiar with this art need a good aerosol. 4 - Excessive experiment can be determined by the pharmaceutical composition of this lx Ming. For example, the operation method of knowing The compound of the present invention _ _ table,, and mouth, can be hunted by the addition of interface activity: First, the water is combined to form a solution. Can be added to help the uniform solution or suspension agent to non-hill price The formation of a square of 4 m. The interface interacts with the compound of the present invention to promote the dissolution of the compound in an aqueous solution delivery system or the compound of the (IV) float. 128409 200836743 The compound of the present invention or a pharmaceutically acceptable compound thereof Salt Is administered in a therapeutically effective amount which will vary depending on a number of factors, including the activity of the particular compound employed; the metabolic stability and length of the compound; the age, weight, general state of health, sex and diet of the patient; Mode and time; excretion rate; drug combination; severity of a particular condition or symptom; and patient being treated. In general, a therapeutically effective dose is (for a 70 kg mammal) about 〇·〇 〇 1 mg / kg (meaning 〇 · 〇 7 mg) to about 100 mg / kg (meaning 7000 grams); therapeutically effective dose is preferably (for 70 kg of mammals) about 0.01 mg / kg (meaning 0.7 mg) to about 50 mg/kg (ie 3.5 g); a therapeutically effective dose is preferably (for a 70 kg mammal) about 1 mg/kg (ie 70 mg) to about 25 mg / kg (meaning 1.75 grams). The effective dosage ranges provided herein are not intended to be limiting, but rather represent preferred dosage ranges. However, the optimal dose is revised for individual patients and is identifiable and measurable by those skilled in the art (see, for example, Berkow et al., Merck Handbook, 16th ed., Merck, Rahway, NJ, 1992). Goodmanetna, Pharmacology Foundation, Goodman and Cilman's Therapeutics, 10th Edition, Pergamon Publishing Company, Elmsford, NY, (2001); Avery's Drug Therapy: Principles and Practices in Clinical Pharmacology and Therapeutics, 3rd Edition , ADIS Publishing Company, Williams and Wilkins, Baltimore, MD. (1987), Ebadi Pharmacology, Little, Brown, Boston (1985); Osolci al., Remington's Medical Sciences, 18th Edition, Mack Publishing Company (Easton) , PA) (199〇); Katzung, Basic and Clinical Pharmacology, Appleton and Lange, Norwalk, CT (1992)). 128409 -110- 200836743 Ning is required for each treatment 曰, 蜊里虱 罝-w $, during the day (if needed). In general, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , . The diagnostic pharmaceutical compound or composition may be administered alone or in combination with a physical disease or other symptom of the pathological disease, or a drug or a drug. The compounds and/or compositions of the invention are administered to any vertebrate, such as a mammal. The recipients are primate subjects (including humans, scorpions;; one of the best objects in the object (including horses, goats, cows, sheep, =), cloven-hoofed ^ ^ ^ ^ ^ pigs) rodents Mammals of animal species (bags, large white gas, rabbits and large squirrels) and carnivorous animals (including r:, dogs). Among birds, the preferred recipient is turkey': other members of the same family. The best recipient is human. For topical application, it is preferred to administer the composition to the corpse according to the invention. For example, the skin surface, mucous membrane, etc., which are adjacent to the desired reading (1) milligram to the hair of the Weike = person ^ The range is for each application, regardless of the purpose of diagnosing the area, side or &gt;alpha treatment to be treated, the severity of the condition and the nature of the topical vehicle employed. Preferably, the cream base is used from about qing to (4) ^^ to make each (four) s... The pharmaceutical composition can be a two-skin composition or a percutaneous roller device (&quot;Pill &quot;). The second/sex compound reservoir, control membrane, liner and contact adhesive: can be used to provide continuous beating, or to deliver the compound of the invention as desired, as desired. 128409 -111 - 200836743 The present invention is also known as "_ρ Μ 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Provides a fast, continuous delay of the active ingredient. The controlled release drug delivery system comprises an osmotic pump system and a dissolved steroid system with a polymer coated reservoir or a drug-polymer matrix formulation. Examples of controlled release systems are shown in U.S. Patent Nos. 770 and 4, Wind Milk, in Kuzma et al., 昼 靡 22 22 (6): 543-551 (Example 7), all of which are incorporated herein by reference. . a composition of the invention may also be transmitted through an intranasal drug delivery system for administration

_二、、、及冗子至腦部醫藥療法用。受控粒子分散（CpD)TM 技術、傳統鼻噴霧劑瓶、吸入器或霧化罐係為熟諳此藝者 已知’以提供藥物之有效局部與系統傳輸，其方式是以嗅 覺區域與鼻旁竇作為標的。 ^明亦Μ於適合投予女性人類或動物之陰道内殼層或 =芯藥物傳輸裝置。此裝置可包含活性醫藥成份在聚合體 基質中’被護套圍繞，且能夠以實質上零級型式，以每曰 為基礎釋出化合物’類似用以施加睪酮之設計，如PCT專 利WO 98/50016中所述。 七、眼部傳輸之現行方法包括局部投藥（眼藥水）、結合膜 '玻璃狀體内注射、手術植入物及離 :/法（利肖小屯流以輸送離子化藥物進入且經過身體 、=)U藝者將合併最良好適合賦形劑與該化合物， 以提供安全且有效眼内投藥。 取適合途徑係依被治療症狀之性質與嚴重性而定。熟諳 此藝者亦熟悉決定投藥方法(口腔、靜脈内、吸入、皮下、 128409 -112- 200836743 直腸等）' 劑型、適當醫藥賦形劑及與化合物傳輸至有需要 病患有關聯之其他事項。 組合療法 本發明化合物可有用地併用一或多種其他本發明化合物 或一或多種其他治療劑或作成其任何組合，以治療鈉通道 所媒介之疾病與症狀。例如，式（I)化合物可併用其他治療 劑，同時、相繼或個別地投予，其包括但不限於： • 阿片製劑止痛劑，例如嗎啡、海洛因、古柯鹼、氧 基嗎啡、經甲左嗎南（levorphanol)、稀丙左嗎喃 (levallorphan)、經基二氫待因酮（oxycodone)、可待因、 二氫可待因、丙氧吩、那美吩（nalmefene)、芬太尼 (fentanyl)、二氫可待因酮、氫莫風（hydromorphone)、美 利皮定（meripidine)、美沙酮（methadone)、丙浠嗎啡、那 諾松（naloxone)、那瑞克松（naltrexone)、丁潑諾吩 (buprenorphine)、環丁 甲二羥嗎喃、那布吩（nalbuphine)及 戊吐星（pentazocine); • 非阿片製劑止痛劑，例如乙St美尼吩（acetomeniphen)、 柳酸鹽（例如阿斯匹靈）； • 非類固醇消炎藥物（NSAro)，例如異丁苯丙酸 (ibuprofen)、那丙新（naproxen)、菲諸丙吩（fenoprofen)、酮 基丙吩（ketoprofen)、塞拉庫西比（celecoxib)、二可吩拿 克（diclofenac)、二氟新諾（diflusinal)、依托多拉克 (etodolac)、聯苯丁酮酸、菲諾丙吩（fenoprofen)、氟吩尼 索（flufenisal)、氟雙丙吩、異丁苯丙酸（ibuprofen)、吲嗓 128409 -113 - 200836743 美薩辛（indomethacin)、酮基丙吩（ketoprofen)、酮洛拉克 (ketorolac)、甲氯滅酸、甲滅酸、美氧胺（meloxicam)、 那布美東（nabumetone)、那丙新（naproxen)、尼美沙利得 (nimesulide)、石肖基氟雙丙吩、歐沙啡（olsalazine)、p号普 羅辛（oxaprozin)、苯基保泰松（phenylbutazone)、口比氧胺 (piroxicam)、硫酸沙 p井（sulfasalazine)、沙林達克（sulindac)、 四苯醯p比哈乙酸（tolmetin)及周美皮克（zomepirac); • 抗搐搦藥，例如胺甲醯氮萆、羧一氮七圜烯、拉莫 三金臬（lamotrigine)、法普酸鹽、托皮拉美（topiramat)、 加巴潘亭（gabapentin)及普瑞加巴林（pregabalin); • 抗抑鬱劑，譬如三環狀抗抑鬱劑，例如阿米替林 (amitriptyline)、可洛米胺（clomipramine)、迪斯普胺 (despramine)、丙。米 p井及諾三替林（nortriptyline); • COX-2選擇性抑制劑，例如塞拉庫西比（celecoxib)、羅 費庫西比（rofecoxib)、培瑞庫西比（parecoxib)、維德庫西 比（valdecoxib)、德拉庫西比（deracoxib)、依托庫西比 (etoricoxib)及魯米庫西比（lumiracoxib); • α-腎上腺素能藥物，例如多氧峻辛（doxazosin)、塔蘇羅 辛（tamsulosin)、可樂寧（clonidine)、胍發辛（guanfacine)、 迪美托米定（dexmetatomidine)、蒙達非尼（modafmil)及4-胺基-6,7-二甲氧基-2·(5-曱烷磺醯胺基-1，2,3,4-四氫異喳 4木-2-基）-5-(2-外匕11定基）0奎°坐^1林； • 巴比妥酸鹽鎮靜藥，例如阿莫巴比妥（amobarbital)、稀 丙異丙巴比妥、仲丁巴比妥、布塔必妥（Butabital)、美 128409 -114- 200836743 發巴比妥（Mephobarbital)、美沙必妥（metharbital)、美梭赫 西妥（methohexital)、戊巴比妥、吩巴比妥（phenobartital)、 司可巴比妥（secobarbital)、塔布妥（talbutal)、席爾密拉 (theamylal)及硫戊妥（thiopental); • 速激肽(NK)拮抗劑，特別是NK-3、NK_2或NK-1拮抗劑， 例如（〇:R，9R)-7-[355-雙（三氟甲基）苄基]-8,9，10，11-四氫-9-甲基-5_(4-甲基苯基）-7Η-[1，4]二氮八圜烯并[2，l-g][l，7]喑 啶-6-13-二酮（TAK-637)、5-[[(2R，3S)_2-[(lR)-l-[3,5-雙（三氟曱 基）苯基]乙氧基-3-(4-氟苯基）-4-嗎福琳基]甲基]-1，2-二 氫-3H-1，2,4-三吐-3-酮（MK-869)、阿瑞皮坦特（aprepitant)、 蘭尼皮坦特（lanepitant)、達皮坦特（dapitant)及3-[[2-曱氧 基-5-(三氟甲氧基）苯基]曱胺基]-2-苯基-六氫吡啶 (2S，3S); • 煤焦油止痛劑，特別是捕熱息痛（paracetamol); • 血清素再攝取抑制劑，例如帕西汀（paroxetine)、色他 林（sertraline)、去甲氟西汀（norfluoxetine)(氟西汀 (fluoxetine)脫甲基新陳代謝產物）、新陳代謝產物去甲 基色他林（demethylsertraline)、f3-氟伯斯胺（fluvoxamine)、 帕西汀（paroxetine)、西塔洛蘭（citalopram)、西塔洛蘭 (citalopram)新陳代謝產物脫甲基西塔洛蘭（citalopram)、 約西塔洛蘭（escitalopram)、d，l-芬弗拉胺（fenfluramine)、非 莫西汀（femoxetine)、愛弗西汀（ifoxetine)、氰基多硫七圜 稀（cyanodothiepin)、利多西汀（litoxetine)、達波西汀 (dapoxetine)、那發坐酮（nefazodone)、些利可胺（cericlamine) 128409 -115- 200836743 、搓 σ坐酮（trazodone)及 西、;丁（fluoxetine); • 去甲腎上腺素（正腎上腺素）再攝取抑制劑，例如馬普 洛替林（maprotiline)、洛非丙胺（lofepramine)、莫塔吉平 (mirtazepine)、氧普替林（oxaprotiline)、非坐胺（fezolamine)、 托莫西&gt;'丁（tomoxetine)、米安斯林（mianserin)、布若普利 翁（buproprion)、布若普利翁（buproprion)新陳代謝產物經 基布若普利翁（hydroxybuproprion)、諾米吩辛（nomifensine) 及威氧畊（viloxazine)(Vivalan®))，尤其是選擇性去甲腎上 腺素再攝取抑制劑，譬如瑞玻西汀（reboxetine)，特別 是（S，S)-瑞玻西丁（reboxetine)，及溫拉發辛（venlafaxine)杜 奥西汀（duloxetine)致類神經病症鎮靜劑/解焦慮劑； • 雙血清素-去甲腎上腺素再攝取抑制劑，譬如溫拉發 辛（venlafaxine)、溫拉發辛（venlafaxine)新陳代謝產物〇-脫甲基溫拉發辛（venlafaxine)、可洛米胺（clomipramine)、 可洛米胺（clomipramine)新陳代謝產物脫甲基可洛米胺 (clomipramine)、杜奥西汀（duloxetine)、米那西普蘭 (milnacipran)及丙味啡； • 乙醯膽鹼酯酶抑制劑，譬如多臬佩吉（donepezil); • 5-HT3拮抗劑，譬如翁丹西從（ondansetron); • 代謝移變麩胺酸酯受體（mGluR)拮抗劑； • 局部麻醉劑，譬如慢心利（mexiletine)與利多卡因； • 皮質類固醇，譬如地塞米松； • 抗節律不齊藥，例如慢心利（mexiletine)與苯妥英； • 蠅蕈鹼拮抗劑，例如托帖洛定（tolterodine)、普吡維林 128409 -116- 200836743 (propiverine)、搓普席姆（tropsium) t氯化物、達里吩那新 (darifenacin)、梭利吩 新（solifenacin)、鐵米伯林 (temiverine)及依普拉搓品（ipratropium); •類大蔴苷； • 類香草素受體催動劑（例如瑞新非拉素（resinferatoxin)) 或拮抗劑（例如辣椒氮平（capsazepine)); • 鎮靜藥，例如苯乙哌啶酮、胺甲丙二酯、安眠酮 (methaqualone)及二氯拉吩腙（dichloralphenazone); • 解焦慮劑，譬如苯并二氮七圜類， • 抗抑營劑，譬如莫塔札平（mirtazapine) • 局部藥劑（例如利多卡因、卡伯沙辛（capsacin)及樹脂非 各素（resiniferotoxin)); • 肌肉鬆弛劑，譬如苯并二氮七圜類、氯苯胺丁酸 (baclofen)、異丙安寧（carisoprodol)、氯吟腙（chlorzoxazone)、 環苯雜林（cyclobenzaprine)、甲卡巴摩（methocarbamol)及歐 弗瑞那定（orphrenadine); • 抗組織胺或吒拮抗劑； • NMDA受體拮抗劑； • 5-HT受體催動劑/拮抗劑； • PDEV抑制劑； • Tramadol® ； • 膽鹼能（菸鹼酸）止痛劑； • α-2- δ配位體； •前列腺素Ε2亞型拮抗劑； 128409 •117- 200836743 •白三浠素B4拮抗劑； • 5-脂肪氧化酶抑制劑；及 • 5-HT3拮抗劑。 可使用此種組合治療及/或預防之納通道所媒介疾病與 症狀，包括但不限於疼痛，中樞與末梢所媒介，急性、慢 性、神經病原性，以及且右古關 Λ及具有有關聯疼痛之其他疾病，及其 他中樞神經病症，譬如癤廟隹麼 .^ Μ m焦慮、抑鬱及兩極疾病；或 心血管病症，譬如節律不齊、心廣 片 U尽纖維顫動及心室纖維顫 動；神經肌肉病症，孽士π χA , 、 吕如不女f腳部徵候簇與肌肉麻痺或 破傷風；抵抗中風、神經損傷及多發性硬化之神經保嘆· 及通道病，譬如肢端紅痛病與家族性直腸疼痛徵候簇。’ 於本文中使用之”組人”仫社 .^ 、口係私一或多種本發明化合物與一 或多種其他本發明化合物或一 一 、 飞次夕種其他治療劑之任何混 合物或替換。除非内文另古、、八 井鬥文另有澄清，否則”組合&quot;可包括同時 或相繼地傳輸本發明化合物與_ 二 $夕種〉口療劑。除非内文 另有澄清，否則Π《且人”·4』 、σ 了匕括本發明化合物與另一種治療 劑之劑型。除非内文另有 緣 有Θ，否則”組合，，可包括本發明 化a物與另一種治療劑 仅+延徑。除非内文另有 否則”組合”可包括本發 σ物與另一種治療劑之配方。 劑型、投藥途徑及醫藥 者。 口物係包括但不限於本文中所述 配件套組 本發明亦提供套組，1含古殿— 八3有西樂組合物，其包含一 種上式化合物。此套組亦包 ^ 二 關於利用該醫藥組合物以調 128409 -118- 200836743 制離子通道活性，治疼、皮、虑 用…明金/α廢疼痛，以及如本文中所揭示其他利 曰。商業包裝較佳係含有-或多個單位劑量之 醫藥組合物。例如，此播罝彳 ^ ^ 此種早位劑量可為足供製備靜脈内注 射之ϊ。一般熟諳此項技蓺者 、 议衣考將顯見的是，光線及/或空氣 敏感之化合物可能需要特殊包 匕衣及/或调配。例如，可使 對光不透明及/或缚穷4+丨、/ a λ四 飞、，、二在封以免與環境空氣接觸及/或以適♦ 塗層或賦形劑調配之包裝。 曰 本發明化合物之製備 下列反應圖式係說明製造本發明化合物之方法，該化合 物意即式（I)化合物： 〇_ Second,, and redundant to the brain for medical therapy. Controlled Particle Dispersion (CpD)TM technology, traditional nasal spray bottles, inhalers, or nebulizers are known to those skilled in the art to provide effective local and systemic delivery of drugs by olfactory areas and nasal passages. The sinus is the target. It is also suitable for intravaginal shell or = core drug delivery devices suitable for administration to female humans or animals. The device may comprise an active pharmaceutical ingredient surrounded by a sheath in a polymeric matrix and capable of releasing the compound on a per-pound basis in a substantially zero-order format, similar to the design used to apply an anthrone, such as PCT Patent WO 98/ Said in 50016. Seven, the current methods of eye transmission include local administration (eye drops), combined membrane 'intravitreal injection, surgical implants and separation: / method (Leisho small turbulent flow to transport ionized drugs into and through the body, =) U artists will combine the most suitable excipients with the compound to provide safe and effective intraocular administration. The appropriate route depends on the nature and severity of the condition being treated. This artist is also familiar with the method of administration (oral, intravenous, inhalation, subcutaneous, 128409-112-200836743 rectum, etc.), dosage forms, appropriate pharmaceutical excipients, and other matters associated with the delivery of the compound to a patient in need. Combination Therapy The compounds of the invention may be used in combination with one or more other compounds of the invention or one or more additional therapeutic agents or any combination thereof to treat the diseases and conditions mediated by the sodium channel. For example, a compound of formula (I) may be administered in combination with other therapeutic agents simultaneously, sequentially or separately, including but not limited to: • Opiate analgesics such as morphine, heroin, cocaine, oxymorphine, guanine left Levorphanol, levallorphan, oxycodone, codeine, dihydrocodeine, propoxyphene, nalmefene, fentanyl (fentanyl), hydrocodone, hydromorphone, meripidine, methadone, acetamidine, naloxone, naltrexone, Buprenorphine, cyclobutanol, nalbuphine, and pentazocine; • non-opioid analgesics, such as acetomeniphen, salicylate (eg aspirin); • NSAro, such as ibuprofen, naproxen, fenoprofen, ketoprofen Celecoxib, dicoleb (diclofe) Nac), diflusinal, etodolac, benzobutyric acid, fenoprofen, flufenisal, fluorodipropion, ibuprofen (ibuprofen), 吲嗓128409 -113 - 200836743 Indomethacin, ketoprofen, ketorolac, meclofenac, mefenamic acid, mexiracene, meloxicam Nabumetone, naproxen, nimesulide, succinyl fluorodiphenyl, olsalazine, poxa oxaprozin, phenylbutazone, Oral piroxicam, sulfasalazine, sulindac, tolmetin and zomepirac; • anticonvulsants, such as amines Methotrexate, carboxynitrile heptatriene, lamotrigine, palmiperate, topiramat, gabapentin, and pregabalin; An antidepressant, such as a tricyclic antidepressant, such as amitriptyline, Clomipramine, despramine, C. Rice wells and nortriptyline; • COX-2 selective inhibitors such as celecoxib, rofecoxib, parecoxib, vitamins Valdecoxib, deracoxib, etoricoxib, and lumiracoxib; • alpha-adrenergic drugs such as doxazosin , tasulosin, clonidine, guanfacine, dexmetatomidine, modafmil, and 4-amino-6,7-dimethyl Oxy-2(5-decanesulfonylamino-1,2,3,4-tetrahydroisoindolyl 4-yl-2-yl)-5-(2-exopurine 11-based) 0 奎 ° sitting ^ 1 forest; • Barbiturate sedatives, such as amobarbital, isopropylbarbital, sec-butyl barbital, Butabital, US 128409-114-200836743 Mephobarbital, metharbital, mesohexital, pentobarbital, phenobartital, secobarbital, tabouto ( Tal Butal), theamylal and thiopental; • tachykinin (NK) antagonists, especially NK-3, NK_2 or NK-1 antagonists, eg (〇: R, 9R) -7-[355-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7Η-[1,4] Diazepamedo[2,lg][l,7]acridine-6-13-dione (TAK-637), 5-[[(2R,3S)_2-[(lR)-l-[ 3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)-4-moffinyl]methyl]-1,2-dihydro-3H-1, 2,4-tripa-3-one (MK-869), aprepitant, lanititant, dapitant, and 3-[[2-oxo -5-(Trifluoromethoxy)phenyl]nonylamino]-2-phenyl-hexahydropyridine (2S, 3S); • Coal tar analgesics, especially paracetamol; Serotonin reuptake inhibitors, such as paroxetine, sertraline, norfluoxetine (fluoxetine demethylation metabolite), metabolite demethylation Demethylsertraline, f3-fluvoxamine, pa Paroxetine, citalopram, citalopram metabolites, citalopram, escitalopram, d,l-fenfluramine, Femoxetine, ifoxetine, cyanodothiepin, litoxetine, dapoxetine, nefazodone, Some cericlamine (128409-115-200836743), trazodone and fluoxetine; • norepinephrine (norepinephrine) reuptake inhibitors, such as maprotiline (maprotiline), lofepramine, mirtazepine, oxaprotiline, fezolamine, tomoxy &gt; tomoxetine, mianserin , buproprion, and buproprion metabolites via hydroxybuproprion, nomifensine, and viloxazine (Vivalan®) Especially selective Adrenalin reuptake inhibitors, such as reboxetine, especially (S, S)-reboxetine, and venlafaxine duloxetine-induced neurological disorders Sedative/anxiolytic agent; • Dual serotonin-norepinephrine reuptake inhibitors, such as venlafaxine, venlafaxine metabolite 〇-demethyl valacin (venlafaxine) , clomipramine, clomipramine metabolites, clomipramine, duloxetine, milnacipran, and propylmorphine; A cholinesterase inhibitor, such as donepezil; • a 5-HT3 antagonist, such as Ondansetron; • a metabolically shifting glutamate receptor (mGluR) antagonist; Local anesthetics, such as mexiletine and lidocaine; • corticosteroids such as dexamethasone; • anti-arrhythmic drugs such as mexiletine and phenytoin; • muscarinic antagonists such as toltello set Tolterodine), propivirin 128409-116-200836743 (propiverine), tropsium t chloride, darifenacin, solifenacin, temiverine ) and ipratropium; • cannabinoids; • vanilloid receptor agonists (eg, resinferatoxin) or antagonists (eg capsazepine); Sedatives such as phenethyl piperidone, amine methyl propylene glycol, methaqualone and dichloralphenazone; • anti-anxiety agents, such as benzodiazepines, • anti-suppressants Such as mottazapine • topical agents (eg lidocaine, capsacin and resiniferotoxin); • muscle relaxants such as benzodiazepines, chlorine Baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, methocarbamol, and orphrenadine; • antihistamine or吒 antagonists; • NMDA receptors Anti-agents; • 5-HT receptor agonists/antagonists; • PDEV inhibitors; • Tramadol®; • Cholinergic (nicotinic acid) analgesics; • α-2- δ ligands; • Prostaglandins Ε2 subtype antagonist; 128409 •117- 200836743 • White triterpene B4 antagonist; • 5-lipoxygenase inhibitor; and • 5-HT3 antagonist. The combination can be used to treat and/or prevent the diseases and symptoms of the passage, including but not limited to pain, central and peripheral mediators, acute, chronic, neuropathogenic, and right ancient and associated pain Other diseases, and other central nervous disorders, such as the temple, ^ m anxiety, depression and bipolar diseases; or cardiovascular disorders, such as irregular rhythms, heart-shaped tablets, fibrillation and ventricular fibrillation; neuromuscular Illness, gentleman π χA, , Lu Ru, female f foot syndrome and muscle paralysis or tetanus; nerve sigh and channel disease against stroke, nerve damage and multiple sclerosis, such as limb red pain and familial Rectal pain syndrome. &quot;Group of persons&quot; as used herein. The oral system is any mixture or substitution of one or more compounds of the invention with one or more other compounds of the invention or one of the other therapeutic agents. Unless otherwise stated in the text, the "combination" may include simultaneous or sequential delivery of the compound of the invention and the remedy for oral therapy, unless the context clarifies otherwise. "And human" 4", σ includes a dosage form of the compound of the present invention and another therapeutic agent. Unless the context otherwise dictates otherwise, "combination," may include the invention and the other therapeutic agent only + extended diameter. Unless otherwise stated herein, the "combination" may include the present sigma and another therapeutic agent. Formulations, dosage forms, and pharmaceuticals. The mouthpieces include, but are not limited to, the kits described herein. The kits also provide kits, and 1 contains the ancient hall-eighth having a celec composition comprising a compound of the above formula. This kit also includes the use of the pharmaceutical composition to adjust the ion channel activity of 128409-118-200836743, to treat pain, skin, and use of ... gold/alpha waste pain, and other benefits as disclosed herein. Preferably, the commercial package contains a pharmaceutical composition of - or a plurality of unit doses. For example, the sowing dose can be used for the preparation of intravenous injections for intravenous injection. Apparently, it is obvious that light and/or air sensitive compounds may require special coatings and/or blending. For example, it may be opaque to light and/or poorly 4+丨, / a λ, Second, in order to avoid contact with ambient air . And / or excipients suitable for formulation of ♦ coating or packaging of said preparation of the compounds of the present invention the following reaction scheme-based method of manufacturing a compound of the present invention, which means that the compound of formula (I) are: square

,R3 1ST (I) Θ 、R2 k 其中，n，Rl，RlR3均如上文在發明内容中關於式⑴化 合物所定義’為其立體異構物、對掌異構物、互變異構物 或其混合物；或其藥學上可接受 佼又I盟，谷劑合物或前體藥 物，其係被使用於本發明之方法中。 應明瞭的是，於下文說明中，所描繪化學式之取代基及/ 或變數之組合只有在此種組合會造成安定化合物時才可允 許。 熟諳此藝者亦應明瞭的是，在下文所述之方法中，中間 化合物之官能基可能必須藉由適當保護基保護。此種官能 基包㈣H基' «及㈣。對經基之適當保護基包 128409 -119- 200836743 括三烷基矽烷基或二芳基烷基矽烷基（例如第三-丁基二甲 基矽烷基、第三-丁基二苯基矽烷基或三甲基矽烷基）、四 氫哌喃基、芊基等。對胺基、甲脒基及胍基之適當保護基 包括第二-丁氧獄基、字氧獄基等。對魏基之適當保護基包 括-C(0&gt;R”（其中R”為烷基、芳基或芳烷基）、對_甲氧基苄 基、三苯甲基等。對羧酸之適當保護基包括烷基、芳基或 芳烧基酯類。 保護基可根據標準技術添加或移除，其係為熟諳此藝者 所已知且如本文中所述。 保護基之使用係詳細描述於Green，T W•與pGM. w他， 代亦硪合成2之保護羞（2006)，第4版，Wiley中。保護 基亦可為聚a體樹脂，譬如樹脂或氯化氯基三苯甲 烧樹脂。 热叫此藝者亦應明瞭的是，雖然本發明化合物之此種經 呆又行生物本身可能未具有藥理學活性，但其可被投予哺 ί動t 4妾著在身體中經生物代謝，以形成具藥理學活性 之本U化合物。此種衍生物可因此被描述為”前體藥物”。 本發明化合物之所有前體藥物係被包含在本發明之範圍 内0 的：列=式係說明製造本發明化合物之方法。應明瞭 = 藝者將能夠藉類似方法或藉熟諸此藝者已知 之方法製造此等介入 夠以類似如下文所、亦應明瞭的是’熟諳此藝者係能 合成參數，按恭二方式，利用適當起始成份，並修正 而而疋，製造未明確地說明於下文之其他 128409 •120· 200836743 本發明化合物。一般而言，起始成份可得自一些來源，譬 如 Sigma Aldrich，Lancaster 合成公司，Maybridge，Matrix Scientific， TCI，及FluoroChem USA等，或根據熟諳此藝者所已知之來源 合成（參閱，例如Smith，Μ·Β.與J. March，高#才满/6學··及 應、襪鈥沒·##，第5版（Wiley，2000年12月））或按本文中所述 製備。, R3 1ST (I) Θ , R2 k wherein n, R1, RlR3 are as defined above in the Summary of the Invention with respect to the compound of formula (1) as its stereoisomer, palmomer, tautomer or A mixture; or a pharmaceutically acceptable oxime thereof, or a pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable pharmaceutically acceptable compound. It should be understood that in the following description, combinations of substituents and/or variables of the formulas depicted may only be permitted if such combinations result in a stability compound. It is also apparent to those skilled in the art that in the methods described below, the functional groups of the intermediate compound may have to be protected by a suitable protecting group. This functional group (IV) H-based '« and (d). Suitable protecting groups for the thiol group 128409-119-200836743 include trialkyldecyl or diarylalkyl decyl groups (eg, tert-butyldimethyl decyl, tert-butyldiphenyl decyl) Or trimethyldecylalkyl), tetrahydropyranyl, fluorenyl and the like. Suitable protecting groups for the amine group, the methyl group and the fluorenyl group include the second-butoxy-phenyl group, the word oxygen base, and the like. Suitable protecting groups for the thiol group include -C(0&gt;R" (wherein R" is alkyl, aryl or aralkyl), p-methoxybenzyl, trityl, etc. Suitable for carboxylic acid Protecting groups include alkyl, aryl or arylalkyl esters.Protective groups can be added or removed according to standard techniques, which are known to those skilled in the art and as described herein. In Green, TW• and pGM. w, he also synthesizes the protection of shy (2006), 4th edition, Wiley. The protective group can also be a poly-a resin, such as resin or chlorotriphenyl chloride. Burning the resin. It is also understood by the artist that although the compound of the present invention may not have pharmacological activity itself, it may be administered to the body. Biologically metabolized to form a pharmacologically active U compound. Such derivatives may thus be described as "prodrugs." All prodrugs of the compounds of the invention are included within the scope of the invention: Column = formula illustrates the method of making the compounds of the invention. It should be understood that the artist will be able to borrow similar parties Or by means of methods known to those skilled in the art to make such interventions as similar to the following, it should also be clear that 'the skilled person can synthesize the parameters, according to the second method, using the appropriate starting ingredients, and correcting制造, the manufacture of other compounds of the invention not explicitly described below is 128409 • 120· 200836743. In general, the starting ingredients can be obtained from a number of sources, such as Sigma Aldrich, Lancaster Synthesis, Maybridge, Matrix Scientific, TCI, and FluoroChem. USA, etc., or synthesized according to sources known to those skilled in the art (see, for example, Smith, Μ·Β. and J. March, Gao #才满/6学··和应,袜鈥没·##,第5 Edition (Wiley, December 2000)) or prepared as described herein.

於下列反應圖式中， 、:^尺沁:^及以均如上文在發明内 容中關於式⑴化合物所定義，除非另有明確定義。 式（la)化合物之製備 式（la)化合物為如上文在發明内容中所提出之式（I)化合 物，其中R3為芳基或雜芳基。式（la)化合物可按照下文反應 rri 圖式1中所述之一般程序合成，其中、n，R1及R2均如上文 在發明内容中關於式（I)化合物所定義，R3a為如上文關於式 (I)化合物中之R3所定義之芳基或雜芳基，且R為烷基： 128409 121 - 200836743 反應圖式1In the following reaction schemes, :, and, as defined above, in the context of the invention, as defined in the context of the compound of formula (1), unless explicitly defined otherwise. Preparation of the compound of the formula (la) The compound of the formula (la) is a compound of the formula (I) as set forth above in the Summary of the Invention, wherein R3 is an aryl group or a heteroaryl group. The compound of formula (la) can be synthesized according to the general procedure described in the following reaction rri Scheme 1, wherein n, R1 and R2 are as defined above for the compound of formula (I), and R3a is as defined above. (I) an aryl or heteroaryl group as defined by R3 in the compound, and R is an alkyl group: 128409 121 - 200836743 Reaction Scheme 1

NH2 - R3a (102)NH2 - R3a (102)

,R3a (103) Ο,R3a (103) Ο

式（101)、式（102)、式（105)及式（107)化合物係為市購可得， 或可根據熟者此藝者已知之方法或藉由本文中所揭示之方 法製備。Compounds of formula (101), formula (102), formula (105) and formula (107) are commercially available or can be prepared according to methods known to those skilled in the art or by the methods disclosed herein.

一般而言’式（la)化合物係如上文在反應圖式1中所述製 成，其方式是首先使式（102)胺化合物與式（ιοί)硝基取代之 氯化酿化合物，於驗譬如但不限於三乙胺存在下反應，而 得式（103)醯胺化合物。然後，可使式（1〇3)化合物中之硝基 還原成其相應之胺基，以產生式（1〇4)化合物，藉由標準還 原方法，譬如但不限於鈀催化之氫化作用、亞硫酸氫鈉還 原作用、氯化錫（II)逛原作用或鋅還原作用。式（1〇4)化合物 以式（105)三烷基原酸酯化合物，較佳為三甲基原酸酯，於 128409 -122 - 200836743 酸譬如但不限於醋酸存在下處理，提供式（Ia)稠合嘧啶酮化 合物。 或者，式（104)化合物可以式（1〇7)醛化合物處理，以形成 經壞化之式（108)化合物。然後，可將式（1〇8)化合物以氧化 劑，譬如但不限於2,3-二氣_5,6-二氰基]，4_苯醌處理，而得式 (la)化合物。 式（la)化合物，其中R3a為含氮雜芳基，可進一步以氧化 劑，譬如但不限於尿素過氧化氯加成化合物，在溶劑譬如 但不限於二氯甲烷中處理，以產生式(Ia)化合物，1中 為經氧化之含氮雜芳基，譬如丨_氧化吡啶基。 八In general, a compound of the formula (la) is prepared as described above in Reaction Scheme 1 by first reacting an amine compound of the formula (102) with a chlorinated compound substituted with a nitro group. For example, but not limited to, the reaction in the presence of triethylamine gives the decylamine compound of formula (103). The nitro group of the compound of formula (1〇3) can then be reduced to its corresponding amine group to yield a compound of formula (1〇4) by standard reduction methods such as, but not limited to, palladium-catalyzed hydrogenation, sub- Reduction of sodium hydrogen sulfate, tin (II) chloride or zinc reduction. The compound of the formula (1〇4) is treated with a trialkyl orthoester compound of the formula (105), preferably a trimethyl orthoester, in the presence of, for example, but not limited to acetic acid, 128409-122 - 200836743, to provide the formula (Ia) a fused pyrimidinone compound. Alternatively, the compound of formula (104) can be treated with an aldehyde compound of formula (1-7) to form a compound of formula (108) which is degraded. Then, the compound of the formula (1〇8) can be treated with an oxidizing agent such as, but not limited to, 2,3-dioxa-5,6-dicyano], 4-benzoquinone to obtain a compound of the formula (la). a compound of formula (la) wherein R 3a is a nitrogen-containing heteroaryl group which may be further treated with an oxidizing agent such as, but not limited to, a urea peroxychloride addition compound in a solvent such as, but not limited to, dichloromethane to yield formula (Ia) The compound, 1 is an oxidized nitrogen-containing heteroaryl group, such as a ruthenium-iridide pyridyl group. Eight

或者， 其中G 式（la)化合物可如下文在反應圖式2中所述製成 ，n，R，Rl，R2及R3a均如上文在發明内容中所定義Alternatively, wherein the compound of formula (la) can be prepared as described below in Reaction Scheme 2, n, R, R1, R2 and R3a are as defined above in the Summary of the Invention

〇 (202) 反應圖式2 〇(R1)h-(aJA〇r ^NHR2\〇 (202) Reaction pattern 2 〇(R1)h-(aJA〇r ^NHR2\

(R1)rT〇人 〇H 〇(R1)rT〇人〇H 〇

(203) (204)(203) (204)

據熟諳此 式⑽)、綱及式(102)化合物係為市購可p 藝者已知之方法或藉由本文中：之：可根 &lt;方法製 128409 -123 - 200836743 備。 一般而言，式（la)化合物可藉由上文反應圖式2中所示之 方法製成，其方式是首先使式（201)烷胺基酯化合物與式 (202)氯化醯化合物，於鹼譬如但不限於三乙胺存在下反應， 而得式（203)醯胺化合物。在標準條件下，於皂化作用時， 式（203)化合物係被轉化成相應之式（204)酸化合物。於醋酸 酐存在下，式（204)化合物係接著在標準條件下被環化，以 形成式（205)哼畊酮化合物。式（205)化合物與式（1〇2)胺化合 物，在溶劑譬如但不限於吡啶中之反應，係提供式（Ia)化合 物。 或者，如上文在反應圖式2中所示之式（205)化合物可藉由 下文在反應圖式2A中所述之方法製成，其中，n，ri及汉2 均如上文在反應圖式2中所述：The compounds of the formula (10)) and the formula (102) are known to be commercially available or can be prepared by the method of: &lt;&lt;&gt;&gt;&gt; method 128409-123 - 200836743. In general, the compound of the formula (la) can be produced by the method shown in the above Reaction Scheme 2 by first reacting the alkylamino ester compound of the formula (201) with the ruthenium chloride compound of the formula (202). The reaction is carried out in the presence of a base such as, but not limited to, triethylamine to give a compound of the formula (203). Under standard conditions, upon saponification, the compound of formula (203) is converted to the corresponding acid compound of formula (204). The compound of formula (204) is then cyclized under standard conditions in the presence of acetic anhydride to form the hydrazine compound of formula (205). The compound of formula (145) and the amine compound of formula (1〇2) are reacted in a solvent such as, but not limited to, pyridine to provide a compound of formula (Ia). Alternatively, the compound of the formula (205) as shown in the above Reaction Scheme 2 can be produced by the method described below in Reaction Scheme 2A, wherein n, ri and Han 2 are as above in the reaction scheme Said in 2:

反應圓式2A 〇 Ο 〇Reaction round 2A 〇 Ο 〇

(201a)(201a)

〇〇

(205)(205)

r2W (301) 式（201a)與式（301)化合物係為市購可得，或可根據熟諳此 藝者已知之方法或藉由本文中所揭示之方法製備。 般而吕，式（205)化合物係藉由上文在反應圖式2A中所 ' 去製成其方式疋使式（201a)胺基魏酸g旨化合物與式 (301)酐化合物，在環境溫度與約18(rc間之溫度下，於溶劑 存在或不存在下反應，以形成式（205)号畊酮化合物。 128409 -124- 200836743 式（lb)化合物之製備 序合成，其中Θ，n，Rl&amp;R2均如上文在發明内容中關於式 (1)化合物所述經定義，R3b為如上文關於式（I)化合物中之R3 所定義之芳基或雜芳基，χ為氯基、溴基、碘基或三氟甲 烧硫酸鹽，且…為院基、環烧基、環炫*基烧基、i烷基、 芳基、芳烷基、雜環基、雜環基烷基、雜芳基或雜芳烷基：r2W (301) Compounds of formula (201a) and formula (301) are commercially available or can be prepared according to methods known to those skilled in the art or by the methods disclosed herein. The compound of the formula (205) is obtained by the method described above in the reaction scheme 2A, and the compound of the formula (201a) and the compound of the formula (301) are used in the environment. The temperature is reacted in the presence or absence of a solvent at a temperature of about 18 (r) to form a ketone compound of the formula (205). 128409 - 124 - 200836743 Preparation of a compound of the formula (lb), wherein Θ, n , Rl &amp; R2 are as defined above in the Summary of the Invention for a compound of formula (1), R3b is an aryl or heteroaryl group as defined above for R3 in the compound of formula (I), hydrazine is a chloro group, a bromo group, an iodo group or a trifluoromethane sulfate, and is a aryl group, a cycloalkyl group, a cycloalkyl group, an i-alkyl group, an aryl group, an arylalkyl group, a heterocyclic group or a heterocyclic alkyl group. , heteroaryl or heteroarylalkyl:

(la-” （lb) 式（lb)化合物為如上文在發明内容中所提出之式①化合 物’其中R3為被KN(H)R5a取代之芳基或雜芳基，其中R5a 為烧基、環燒基、環烧基烧基、画烧基、芳基、芳烧基、 雜環基、雜環基燒基、雜芳基或雜芳烧基，且R6a為直接鍵 結。式（lb)化合g可按照下文在反應圖式3中所述之一般程 反應囷式3 式（la-1)化合物為如本文所製成之式（Ia)化合物。式（4〇1)化 合物係為市購可得，或可根據熟諳此藝者已知之方法製備。 一般而言’式（lb)化合物係藉由上文在反應圖式3中所示 之方法製成’其方式是首先將式卩心丨）化合物，其中yb為被 氯基、溴基或碘基或被三氟甲烷硫酸鹽取代之芳基或雜芳 基環’於標準Buchwald/Hartwig胺化反應條件（參閱Muci，A. R. 等人，禮作允學論題（2002)，219: 131)下，以式（401)胺化合 物’於把觸媒存在下，譬如但不限於肆（三苯膦）把⑼或參（二 苯亞甲基丙酮）二鈀（〇)，使用或未使用配位體，譬如但不限 128409 -125 - 200836743 於二苯膦、二（鄰-甲笨基）膦、^广雙（二苯基膦基）二環戊二 稀鐵或2-(一-第二-丁基膦基）聯苯，及驗，譬如但不限於碳 酸鈉、碳酸铯或第三-丁醇鈉，在溶劑譬如但不限於二氧陸 圜或四氫呋喃中處理，以產生式（Ib)化合物。 式（Id)、式（Ie)、式（if)及式（Ig)化合物之製備 式（Id)化合物為如上文在發明内容中所提出之式⑴化合 物’其中R3為被KN(H)R5b取代之芳基或雜芳基，其中yb 為-C(0)R4、-C(0)〇R4或-S(0)tR4，其中t與R4均如上文在發明 内谷中所定義’且R6a為直接鍵結。式（Ie)化合物為如上文在 發明内容中所提出之式(I)化合物，其中R3為被 取代之芳基或雜芳基，其中R6a為直接鍵結。式（If)化合物 為如上文在發明内容中所提出之式⑴化合物，其中R3為被 +6a-N(H)C(=NH)NH2取代之芳基或雜芳基，其中心為直接鍵 結。式（Ig)化合物為如上文在發明内容中所提出之式①化合 物，其中R3為被-R6a-N(H)C(=NH)N(H)CN取代之芳基或雜芳 基，其中R6a為直接鍵結。式（Id)、式（le)、式（If)及式（Ig)化 g勿可按照下文在反應圖式4中所述之一般程序合成，其中 ，n，R1及R2均如上文在發明内容中關於式①化合物所述 經定義，R3c為如上文關於式（I)化合物中之R3所定義之芳基 或雜芳基，Boc為第三-丁氧幾基，且R5 b為_c(0)R4、-C(0)0R4 或、s(〇)tR4 : 128409 -126 - 200836743(la-"(lb) The compound of formula (lb) is a compound of formula 1 as set forth above in the Summary of the Invention wherein R3 is an aryl or heteroaryl group substituted by KN(H)R5a, wherein R5a is alkyl, a cycloalkyl group, a cycloalkyl group, a pyrenyl group, an aryl group, an aryl group, a heterocyclic group, a heterocyclic group, a heteroaryl group or a heteroaryl group, and R6a is a direct bond. The compound g can be a compound of the formula (la) prepared according to the general formula described below in the reaction scheme 3, wherein the compound of the formula (Ia) is a compound of the formula (Ia). It is commercially available or can be prepared according to methods known to those skilled in the art. In general, the compound of the formula (lb) is produced by the method shown in the above Reaction Scheme 3, and the manner is first a compound wherein yb is an aryl or heteroaryl ring substituted by a chloro, bromo or iodo group or a trifluoromethane sulfate in standard Buchwald/Hartwig amination conditions (see Muci, AR et al. People, et al. (2002), 219: 131), with the formula (401) amine compound 'in the presence of a catalyst, such as but not limited to bismuth (triphenyl) (9) or ginseng (diphenylmethyleneacetone) dipalladium (ruthenium) with or without a ligand, such as, but not limited to, 128409 -125 - 200836743 in diphenylphosphine, di(o-o-phenyl)phosphine , ^ bis (diphenylphosphino) dicyclopentadienyl iron or 2-(mono-second-butylphosphino) biphenyl, and such as, but not limited to, sodium carbonate, barium carbonate or third - Sodium butoxide, which is treated in a solvent such as, but not limited to, dioxane or tetrahydrofuran to yield a compound of formula (Ib). Formulations of compounds of formula (Id), formula (Ie), formula (if) and formula (Ig) The (Id) compound is a compound of the formula (1) as set forth above in the Summary of the Invention wherein R3 is an aryl or heteroaryl group substituted by KN(H)R5b, wherein yb is -C(0)R4, -C(0 〇R4 or -S(0)tR4, wherein t and R4 are both as defined above in the inner valley of the invention and R6a is a direct bond. The compound of formula (Ie) is as set forth above in the Summary of the Invention (I) a compound wherein R3 is a substituted aryl or heteroaryl group, wherein R6a is a direct bond. A compound of formula (If) is a compound of formula (1) as set forth above in the Summary of the Invention, wherein R3 is +6a-N (H) C(=NH)NH2 substituted aryl or heteroaryl group, the center of which is a direct bond. The compound of formula (Ig) is a compound of formula 1 as set forth above in the Summary of the Invention, wherein R3 is -R6a -N(H)C(=NH)N(H)CN substituted aryl or heteroaryl, wherein R6a is a direct bond. Formula (Id), Formula (le), Formula (If) and Formula (Ig) G may not be synthesized according to the general procedure described below in Reaction Scheme 4, wherein n, R1 and R2 are as defined above for the compound of formula 1 in the Summary of the Invention, R3c is as defined above for Formula (I) An aryl or heteroaryl group as defined by R3 in the compound, Boc is a third-butoxy group, and R5 b is _c(0)R4, -C(0)0R4 or s(〇)tR4: 128409 -126 - 200836743

rid)Rid)

R3c—N A | Ϊ y~NH2 N 八 R2 0 (R1)r q 反應囷式4 .R3c—N(H)R5b N，'ΜR3c—N A | Ϊ y~NH2 N 八 R2 0 (R1)r q Reaction 囷4 .R3c—N(H)R5b N,'Μ

(If) (&gt;g)(If) (&gt;g)

式⑽化合物可根據本文所述之方法製成。式⑽）化合物 係為市購可得’或可根據熟諳此藝者已知之方法製備。 一般而言，如上文在反應圖式4中所述，式（lc)胺基化合 物了以基或〜基_化物試劑，於驗譬如但不限於三乙 胺或二異丙基乙胺存在下處理，以提供式（Id)化合物。或者， 式（Ic)胺基化合物與氰酸鉀，於酸譬如但不限於醋酸存在下 之反應，產生式（Ie)脲化合物。或者，式（ic)胺基化合物可 與試劑譬如但不限於二醯亞胺基硫基三碳酸〇,〇_二-第三_ 丁酯（式（501)彳匕合物），在標準條件下反應，接著為氮之去 除保護，而得式（If)胍化合物。或者，式（Ic)胺基化合物可 128409 -127- 200836743 與鈉二氰基胺，在酸性媒質中反應，以形成式（Ig)氰胍化合 物。 式（K)與式（Ij)化合物之製備 式（Ii)化合物為如上文在發明内容中所提出之式（I)化合 物，其中R3為被-R6a_N(R4a)PG取代之芳基或灕芳基，其中一 為烷基、環烷基烷基、_烷基或雜環基烷基，R6a為直接鍵 結，且PG為氮保護基。式（Ij)化合物為如上文在發明内容中 所提出之式（I)化合物，其中R3為被-R6a-N(R4a)H取代之芳基 或雜芳基，其中為烷基、環烷基烷基、㊂ 烧基’且R6 a為直接鍵結。式⑼與式⑼化名 在反應圖式5中所述之一般程序合成，其中 均如上文在發明内容中關於式①化合物所 為如上文關於式（I)化合物中之R3所定義之交 X為碘基、溴基或氯基，且R4a為烷基、環火 基或雜環基烷基： X為峨基、 、壤院基烷基、齒烷基或雜環基 式（Ii)與式（Ij)化合物可按照下文 程序合成，其中G，n，R1及R2 於式（I)化合物所述經定義，r3 d 之R所定義之芳基或雜芳基， R4a為烷基、環烷基烷基、鹵烷 n，R1 及 R2 反應囷式5Compounds of formula (10) can be made according to the methods described herein. The compound of the formula (10)) is commercially available or can be prepared according to a method known to those skilled in the art. In general, as described above in Reaction Scheme 4, the amine compound of formula (lc) is in the presence of a amide or a amide reagent in the presence of, but not limited to, triethylamine or diisopropylethylamine. Treatment to provide a compound of formula (Id). Alternatively, the reaction of an amine compound of formula (Ic) with potassium cyanate in the presence of an acid such as, but not limited to, acetic acid produces a urea compound of formula (Ie). Alternatively, the formula (ic) amine compound can be combined with a reagent such as, but not limited to, bismuthimidothiotricarbonate, ruthenium-di-tertiary-butyl ester (formula (501) conjugate), under standard conditions The next reaction, followed by nitrogen removal protection, gives the compound of the formula (If). Alternatively, the amine compound of formula (Ic) can be reacted with sodium dicyanoamine in an acidic medium to form a cyanoguanidine compound of formula (Ig) 128409 -127-200836743. Preparation of Compounds of Formula (K) and Formula (Ij) The compound of formula (Ii) is a compound of formula (I) as set forth above in the Summary of the Invention wherein R3 is an aryl or anthracene substituted by -R6a_N(R4a)PG a group, one of which is an alkyl group, a cycloalkylalkyl group, an alkyl group or a heterocyclyl group, R6a is a direct bond, and PG is a nitrogen protecting group. The compound of the formula (Ij) is a compound of the formula (I) as set forth above in the Summary of the Invention, wherein R3 is an aryl or heteroaryl group substituted by -R6a-N(R4a)H, wherein is an alkyl group, a cycloalkyl group Alkyl, trialkyl' and R6 a are direct bonds. The general formula of the formula (9) and the formula (9) are synthesized in the general scheme described in the reaction scheme 5, wherein the compound of the formula 1 is as described above in the context of the invention, and the radical X as defined above for the compound of the formula (I) is iodine. a group, a bromo group or a chloro group, and R 4a is an alkyl group, a cycloalkyl group or a heterocyclic group alkyl group: X is a fluorenyl group, a phosphonyl group, a dentate group or a heterocyclic group (Ii) and a formula (I) Ij) The compound can be synthesized according to the following procedure, wherein G, n, R1 and R2 are as defined in the compound of formula (I), aryl or heteroaryl as defined by R, r3d, R4a is alkyl, cycloalkyl Alkyl, haloalkyl n, R1 and R2 reaction formula 5

式（Ih)化合物可根據本文中 (U) 所述之方法， 或藉熟諳此藝者 128409 -128. 200836743 已知之方法製成。式（601)化合物係為市購可得，或可根據 熟諳此藝者已知之方法製成。 一般而言，如上文在反應圖式5中所述，式（m)經保護胺 基化合物可以強鹼，譬如但不限於氫化鈉，在非質子性溶 劑’譬如但不限於四氫呋喃或N，N-二甲基曱醯胺中處理， 以形成中間物陰離子，其可與式（601)親電子性化合物反應， 以形成式（Π)化合物。式（Π)化合物在標準條件不之去除保 護，以移除保護基’係提供式（Ij)胺基化合物。 式（Im)與式（1〇)化合物之製備 式（Im)化合物為如上文在發明内容中所提出之式①化合 物，其中R3為被-R6a-N(H)_R6b_〇R5取代之芳基或雜芳基，其 中R5係如上文在發明内容中所述，R6a為直接鍵結，且R0b 為被-OR1 4取代之次烷基鏈，其中Ri4為氫、烷基、_烧基、 環烧基、環烧基烧基、芳基、芳烧基、雜環基、雜環基烧 基、雜芳基或雜芳烷基。式（1〇)化合物為如上文在發明内容 中所提出之式（I)化合物，其中R3為含氮雜環基，其中氮係 被-R6b-OR5取代，其中R5係如上文在發明内容中所述，且R0b 為被-OR14取代之次烷基鏈，其中Ri 4為氫、烷基、鹵烷基、 環烷基、環烷基烷基、芳基、芳烷基、雜環基、雜環基烷 基、雜芳基或雜芳烷基。式（Im)與式（1〇)化合物可按照下文 在反應圖式6中所述之一般程序合成，其中 Q n，R1，R2 及 R5均如上文在發明内容中關於式⑴化合物所述經定義，RSe 為如上文關於式（I)化合物中之R3所定義之芳基或雜芳基， 128409 -129- 200836743The compound of the formula (Ih) can be produced according to the method described in (U) herein, or by a method known from the art of 128409-128. 200836743. The compound of formula (601) is commercially available or can be made according to methods known to those skilled in the art. In general, as described above in Reaction Scheme 5, the protected amine compound of formula (m) can be a strong base such as, but not limited to, sodium hydride, in an aprotic solvent such as, but not limited to, tetrahydrofuran or N, N. Treatment with dimethyl decylamine to form an intermediate anion which can be reacted with an electrophilic compound of formula (601) to form a compound of formula (Π). The compound of formula (Π) is not removed under standard conditions to remove the protecting group to provide the amine compound of formula (Ij). Preparation of a compound of the formula (Im) and a compound of the formula (1) The compound of the formula (Im) is a compound of the formula 1 as set forth above in the Summary of the Invention, wherein R3 is substituted by -R6a-N(H)_R6b_〇R5 Or a heteroaryl group, wherein R5 is as described above in the Summary of the Invention, R6a is a direct bond, and R0b is an alkylene chain substituted by -OR14, wherein Ri4 is hydrogen, alkyl, _alkyl, Cycloalkyl, cycloalkyl, aryl, aryl, heterocyclyl, heterocyclyl, heteroaryl or heteroarylalkyl. A compound of formula (1) is a compound of formula (I) as set forth above in the Summary of the Invention, wherein R3 is a nitrogen-containing heterocyclic group wherein the nitrogen is substituted by -R6b-OR5, wherein R5 is as hereinbefore described in the Summary And R0b is a secondary alkyl chain substituted by -OR14, wherein Ri 4 is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, Heterocyclylalkyl, heteroaryl or heteroarylalkyl. Compounds of formula (Im) and formula (1〇) can be synthesized according to the general procedure described below in Scheme 6 wherein Q n, R1, R2 and R5 are as described above for the compound of formula (1) in the Summary of the Invention. Definitions, RSe is an aryl or heteroaryl group as defined above for R3 in the compound of formula (I), 128409-129-200836743

NH 且 表示含氮雜環基·· 反應圖式6NH and represent a nitrogen-containing heterocyclic group · reaction pattern 6

(Ik) (R1), R3e-NH2 'R2(Ik) (R1), R3e-NH2 'R2

、N，'R2 (In) R5 r\,N,'R2 (In) R5 r\

~NH OH 0m)~NH OH 0m)

• 一、 f 厂η znL ^ -4- 製成。式 (701)化合物係為市購可得。 一般而言，式（Ik)胺基化合物或 氧基化合物’在醇性溶劑譬如但不限於異：物以式⑽)環 係個別提供式㈣化合物與式⑽化合物:_中之處理， /斤有本發明化合物’其係以自由態驗或酸形式存在，可 經由以適當無機或有機鹼或酸處 。 知之太土 处理猎由熟諳此藝者已 介人从 予j接叉之鹽。此處所製成 甘ώ丄 苓匕知之軚準技術，被轉化成 /、目由態驗或酸。 【實施方式】 下述製備，其係針對製備本發明化合物中所使用中間物 之=備，及下述實例，其係針對本發明化合物之製備，係 被提供作為一項指引，以幫助本發明之實施，並不意欲作 128409 -130- 200836743 為對本發明範圍之限制。 製備1 2-胺基-N-(4-甲氧苯基）苯甲醯胺之合成 Α· N-(4-甲氧苯基）-2_硝基苯甲酿胺之合成 將2-氯化硝基苯甲醯（2.52克，12.2毫莫耳）在N，N-:甲基甲 醯胺（5毫升）中之溶液，於〇°c下，慢慢添加至對-甲氧基苯 月女（1.5克’ 12.2毫莫耳）、三乙胺（3.4毫升，24.4毫莫耳）在n，N_ 二甲基甲醯胺（15毫升）中之冰冷溶液内。將混合物於〇〇c下 搜拌一小時’並倒入水（300毫升）中。以醋酸乙酯（3 x 5〇毫 升）萃取此懸浮液。將合併之有機層以飽和碳酸鈉溶液與水 洗務’以無水硫酸鈉脫水乾燥，及過溏。在真空中濃縮濾 液，獲得N-(4-甲氧苯基)-2-琐基苯曱醯胺（3.1克，94%)，為無 色固體：4 NMR (300 MHz，CDC13) δ 8.09 (d，J = 8·2 Hz，1H)， 7.77-7.39 (m，6H)，6·88 (d，J = 8·2 Hz，2H)，3.80 (s，3H)· B· 胺基_化(4_甲氧苯基）苯甲醯胺之合成 N-(4-甲氧苯基）-2-石肖基苯曱醯胺（3.1克，11.4毫莫耳）在曱醇 (150毫升）中之懸浮液係經由使氮起泡經過一小時而被脫 氣，然後添加Pd/C (10%，0.6克，0.57毫莫耳）。連接氫氣瓶， 並將反應混合物於環境溫度下攪拌十六小時。使混合物經 過矽藻土墊過濾，在真空中濃縮濾液。使殘留物自醋酸乙 酯與己烷再結晶，而得2-胺基甲氧苯基）苯曱醯胺（2.11 克，76.5%)，為褐色固體：熔點 115-118°C ; iHNMR (300 MHz， CDC13) (5 7·63 (br，1H)，7.48-7.40 (m，3H)，7.27-7.19 (m，1H)，6.93-6.85 (m5 2H)5 6.73-6.65 (m? 2H)? 5.67-5.32 (br? 2H)5 3.80 (s? 3H)； 13 C NMR (75 128409 -131 - 200836743 MHz, CDC13) (5 167.9, 157.1, 149.4, 133.1, 131.2, 127.5, 123.0, 117.9, 117.2, 116.7, 114.7, 56.0. 製備2 2-丁基-4H-3，1-苯并崎畊-4-酮之合成 將鄰胺基苯曱酸（10.0克，73.0毫莫耳）與戊酸酐（37.〇毫升， 173宅莫耳）混合’並於130 C下回流三小時。在高真空下移 除過量戊酸酐，而得2-丁基-4H-3，1-苯并呤畊斗酮（11.0克， 74%)，為油性產物：1 η NMR (300 MHz，CDC13) δ 8.20-8.14 (m，1H)， 7.81-7.74 (m，1Η)，7.57-7.44 (m，2Η)，2·67 (t，J = 7.3 Ηζ，3Η)，1.86-1.73 (m，2H)，1.50-1.36 (m，2H)，0·95 (t，J = 7·3 Hz，3H). 製備3 2-胺基-N-(4-胺甲贐基苯基）苯甲酸胺之合成 Α· N-(4-胺甲醯基苯基）_2·确基苯甲醯胺之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用4-胺基笨曱醯胺置換對-甲氧基苯胺，獲得N_(4_胺甲醯 基苯基）-2-蛾基苯甲醯胺（72%)，為無色固體：ms (ES+) m/z 286.2 (Μ + 1). Β· 2-胺基_Ν-(4_胺甲醯基苯基）苯甲醯胺之合成 按照如製備1Β中所述之程序，且施行無關緊要之改變， 使用Ν-(4-胺甲醯基苯基）_2_确基苯甲醯胺置換Ν_(4_甲氧基-苯 基）2-補基本甲酿胺，獲得胺基_ν_(4_胺甲酿基苯基）苯甲酸 胺（82/〇) ’ 為無色固體：1 η nmR (300 MHz，CD3 〇D) d 7.91-7.76 (m， 4H)? 7.61 (d5 J = 7.9 Hz5 1H), 7.24 (t? J = 7.9 Hz5 1H)? 6.79 (d? J = 8.2 Hz5 1H)，6.69 (t，J = 8.2 Hz，1H). 128409 -132- 200836743 製備4 H[(2-胺基苯基機基]胺基}_2,3_二氫_ΐΗ_ρ?丨哚+羧酸第三-丁 酯之合成 A· 硝基J，3-二氫_1H_吲哚+鲮酸第三-丁酯之合成 於5-硝基吲哚啉（ο·%克，3 〇毫莫耳）與二碳酸二_第三-丁 酯（0.97克，4.4耄莫耳）在無水四氫呋喃（1〇毫升）中之經攪拌 溶液内，在環境溫度下，添加4_二甲胺基吡啶队〇54克，〇 44 毫莫耳）。將反應混合物於6〇°c下攪拌三小時。慢慢添加水， 以使反應淬滅。將反應混合物倒入飽和碳酸氫鈉溶液（1〇〇 毫升）中。以醋酸乙酯（3x30毫升）萃取混合物。使合併之有 機層以無水硫酸鈉脫水乾燥，及過濾。在真空中濃縮濾液， 獲得5-確基-2,3-二氫-1H-啕哚小羧酸第三_ 丁酯（〇·77克， 98%)，為褐色固體：1H NMR (300 MHz，CDC13) 5 8.07 (dd，J = 9_0, 2.4 Hz，1H)，7.97 (d，J - 1.2 Hz，1H)，7.94-7.50 (br，1H)，4.06 (t，J = 8.8• One, f factory η znL ^ -4- made. The compound of formula (701) is commercially available. In general, the amine compound of the formula (Ik) or the oxy compound 'in the alcoholic solvent, such as, but not limited to, the heterocyclic ring of the formula (10), provides a compound of the formula (IV) and the compound of the formula (10): There are compounds of the invention which are present in free form or in acid form, via suitable inorganic or organic bases or acids. Knowing the terroir. Dealing with hunting by the artist has introduced the salt from the j. The quasi-techniques produced here are transformed into /, the purpose of the test or acid. [Embodiment] The following preparations are prepared for the preparation of the intermediates used in the compounds of the present invention, and the following examples, which are provided for the preparation of the compounds of the present invention, are provided as a guide to assist the present invention. The implementation is not intended to be limited to the scope of the present invention by 128409-130-200836743. Preparation of 1-Amino-N-(4-methoxyphenyl)benzamide. Synthesis of N-(4-methoxyphenyl)-2-nitrobenzamide A solution of nitrobenzamide (2.52 g, 12.2 mmol) in N,N-:methylcarbamide (5 mL), slowly added to p-methoxybenzene at 〇 °c Months (1.5 g ' 12.2 mmol), triethylamine (3.4 ml, 24.4 mmol) in ice-cold solution in n,N-dimethylformamide (15 ml). Mix the mixture under 〇〇c for one hour' and pour into water (300 ml). This suspension was extracted with ethyl acetate (3 x 5 Torr). The combined organic layers were dried over anhydrous sodium sulfate as a saturated aqueous solution of sodium carbonate and water and dried. The filtrate was concentrated in vacuo to give N- <RTI ID=0.0>(4- </RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; , J = 8·2 Hz, 1H), 7.77-7.39 (m, 6H), 6·88 (d, J = 8·2 Hz, 2H), 3.80 (s, 3H)· B· Amine _ Synthesis of 4-methoxyphenyl)benzamide A suspension of N-(4-methoxyphenyl)-2-sinylbenzamide (3.1 g, 11.4 mmol) in methanol (150 mL) The liquid system was degassed by bubbling nitrogen for one hour and then Pd/C (10%, 0.6 g, 0.57 mmol) was added. The hydrogen cylinder was connected and the reaction mixture was stirred at ambient temperature for sixteen hours. The mixture was filtered through a pad of Celite, and filtrate was concentrated in vacuo. The residue was recrystallized from ethyl acetate and hexane to give 2-aminomethoxyphenylphenyl phenylamine (2.11 g, 76.5%) as a brown solid: m.p. MHz, CDC13) (5 7·63 (br, 1H), 7.48-7.40 (m, 3H), 7.27-7.19 (m, 1H), 6.93-6.85 (m5 2H) 5 6.73-6.65 (m? 2H)? 5.67-5.32 (br? 2H)5 3.80 (s? 3H); 13 C NMR (75 128409 -131 - 200836743 MHz, CDC13) (5 167.9, 157.1, 149.4, 133.1, 131.2, 127.5, 123.0, 117.9, 117.2, 116.7, 114.7, 56.0. Preparation 2 Synthesis of 2-butyl-4H-3,1-benzoxan-4-one. o-Aminobenzoic acid (10.0 g, 73.0 mmol) with valeric anhydride (37) 〇ml, 173 house moles) mixed' and refluxed at 130 C for three hours. Excess valeric anhydride was removed under high vacuum to give 2-butyl-4H-3,1-benzopyrene 11.0 g, 74%), oily product: 1 η NMR (300 MHz, CDC13) δ 8.20-8.14 (m, 1H), 7.81-7.74 (m, 1 Η), 7.57-7.44 (m, 2 Η), 2· 67 (t, J = 7.3 Ηζ, 3Η), 1.86-1.73 (m, 2H), 1.50-1.36 (m, 2H), 0·95 (t, J = 7·3 Hz, 3H). Preparation 3 2- Amino-N-(4-amine-methylmercaptobenzene Synthesis of benzoic acid amine · Synthesis of N-(4-aminoformylphenyl)_2·decylbenzimidamide According to the procedure as described in Preparation 1A, and irrelevant changes are applied, 4- Substituting amidinobenzamine for p-methoxyaniline to give N_(4-aminoformamidophenyl)-2-dopylbenzamide (72%) as a colorless solid: ms (ES+) m/ z 286.2 (Μ + 1). The synthesis of 2-amino-2-yl-(4-aminomethylphenyl)benzamide is carried out according to the procedure described in Preparation 1Β, and the irrelevant changes are carried out, Displacement of Ν-(4-methoxy-phenyl)2-compound basecartoamine with Ν-(4-aminomethylphenylphenyl)-2-debenzylamine, to obtain the amine group _ν_(4_amine Alkyl phenyl)benzoic acid amine (82/〇) ' is a colorless solid: 1 η nmR (300 MHz, CD3 〇D) d 7.91-7.76 (m, 4H)? 7.61 (d5 J = 7.9 Hz5 1H), 7.24 (t? J = 7.9 Hz5 1H)? 6.79 (d? J = 8.2 Hz5 1H), 6.69 (t, J = 8.2 Hz, 1H). 128409 -132- 200836743 Preparation of 4 H[(2-Aminophenyl) Alkyl}_2,3_Dihydro-ΐΗ_ρ?丨哚+carboxylic acid tert-butyl ester synthesis A·Nitro J,3-dihydro_1H_吲哚+citrate third-butyl ester Synthesis 5-Nitroporphyrin (ο·% g, 3 〇 mmol) and di-tert-butyl dicarbonate (0.97 g, 4.4 Torr) stirred in anhydrous tetrahydrofuran (1 mL) In the solution, at a temperature of ambient temperature, 54 g of 4-dimethylaminopyridine was added, and 〇44 mmol was added. The reaction mixture was stirred at 6 ° C for three hours. Water was slowly added to quench the reaction. The reaction mixture was poured into a saturated sodium hydrogen carbonate solution (1 mL). The mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the titled---- <RTI ID=0.0># </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; , CDC13) 5 8.07 (dd, J = 9_0, 2.4 Hz, 1H), 7.97 (d, J - 1.2 Hz, 1H), 7.94 - 7.50 (br, 1H), 4.06 (t, J = 8.8

Hz，2H)，3.14 (t，J = 8·8 Hz，2H)，1.55 (s，9H). B· 5·胺基-2,3-二氫丨嗓小致酸第三-丁酯之合成 知：&amp;如製備1B中所述之程序’且施行無關緊要之改變， 使用5-硝基-2,3-二氫-1H-吲哚-1-羧酸第三-丁酯置換n_(4_甲氧 基-苯基）-2-硝基苯曱醯胺，獲得5-胺基-2,3-二氫丨嗦+魏 酸第三·丁酯（100%) ·· MS (ES+) m/z 235.2 (M + 1). C· 5-{[(2-确基苯基）擬基】胺基}_2,3_二氫丨嗓小緩酸第： -丁酯之合成 按照如製備1A中所述之程序’且施行無關緊要之改變， 使用5-胺基-2,3-二氫-1H-W哚-1-羧酸第三-丁酯置換對·甲氧 128409 -133 - 200836743 基苯胺，獲得5-{[(2-硝基苯基）幾基]胺基卜2,3·二氫_1Η,噪小 羧酸第三-丁酯（100%) : MS (ES+) m/z 384.2 (M + 1)· D· 5_{[(2·胺基苯基）叛基]胺基卜2,3_二氫-1H-W哚小羧酸第三 -丁酯之合成 知：恥如製備1B中所述之程序，且施行無關緊要之改變， 使用5-{[(2-硝基苯基）幾基]胺基卜2,3-二氫_m_吲哚酸第 二-丁酯置換N-(4-甲氧基-苯基）_2_硝基-苯甲醯胺，獲得5_{[(2_ 胺基苯基）魏基]胺基卜2,3-二氫-1H-W哚-1-羧酸第三·丁醋 (90%) ： MS (ES+) m/z 354.2 (Μ + 1). 製備5 2-胺基-N-(4-胺磺醯基苯基）苯甲醯胺之合成 A· 2_硝基-N-(4-胺磺醯基苯基）苯甲醯胺之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用對胺基苯磺醯胺置換對-甲氧基苯胺，於管柱層析純化 後，獲得2-硝基-N-(4-胺磺醯基苯基）苯甲醯胺（1〇%)，為無色 固體：MS (ES+) m/z 322.2 (M + 1). Β· 2_胺基·Ν-(4-胺磺醯基苯基）苯甲醯胺之合成 按知如製備1B中所述之程序，且施行無關緊要之改變， 使用2-硝基-N-(4-胺磺醯基苯基）苯甲醯胺置換N_⑷甲氧基·苯 基&gt;2-石肖基苯㈣胺，於管柱層析純化後，獲得2_胺基娜_ 胺磺醯基苯基)苯甲醯胺(47%)，為無色固體：MS⑽+)心 292.2 (Μ + 1). 製備6 M[(2-胺基苯基）幾基]胺基}苯甲酸曱酯之合成 128409 -134- 200836743 Α· 4-{[(2-硝基苯基）擬基]胺基}苯甲酸甲酿之合成 按照如製備1Α中所述之程序，且施行無關緊要之改變， 使用4-胺基苯甲酸甲酯置換對-曱氧基苯胺，獲得4_{[(2-硝基 苯基）羰基]胺基}苯甲酸甲酯（90%) : MS (ES+) m/z 301_1 (M + 1&gt;. Β· 4-{[(2-胺基苯基）羰基】胺基}苯甲酸甲酯之合成 按照如製備1Β中所述之程序，且施行無關緊要之改變， 使用4-{[(2-石肖基苯基豫基]胺基}苯甲酸甲酯置換ν_(4_甲氧基 -苯基）-2·硕基苯甲醯胺，獲得4-{[(2-胺基苯基）幾基]胺基）苯 甲酸甲酉旨（50%) : 1 H NMR (300 MHz，CD3 OD) 5 8·03 (d，J = 8.5 Ηζ， 2Η)，7·92 (s，1Η)，7.65 (d，J = 8.5 Ηζ，2Η)，7.46 (d, J = 7.9 Ηζ，1Η)， 7.29-7.21 (m，1H)，6.74-6.65 (m，2H)，5.50 (br，2H)，3.89 (s，3H). 製備7 5-{[(2-胺基苯基）魏基]胺基}-iH_吲嗓-i-羧酸第三_丁醋之合成 A· 5-硝基-1H-峋哚-1-羧酸第三-丁酯之合成 知:如如製備4A中所述之程序’且施行無關緊要之改變， 使用5-硝基-1H-H丨哚置換5-硝基吲哚啉，獲得5_硝基丨嗓 -1-羧酸第三-丁酯（98%) : 1H NMR (300 MHz，CDC13) 5 8.47 (d，J = 2.0 Hz，1H)，8.28-8.15 (m，2H)，7_72 (d，J = 3·5 Hz，1H)，6.70 (d，J = 3·5Hz, 2H), 3.14 (t, J = 8·8 Hz, 2H), 1.55 (s, 9H). B·5·Amino-2,3-dihydroindole small acid-acidic third-butyl ester Synthetic knowledge: &amp; As described in Preparation 1B 'and the insignificant change, using 5-nitro-2,3-dihydro-1H-indole-1-carboxylic acid tert-butyl ester to replace n_ (4-methoxy-phenyl)-2-nitrophenylguanamine to give 5-amino-2,3-dihydroanthracene + tributyl butyl ester (100%) · · MS ( ES+) m/z 235.2 (M + 1). C· 5-{[(2-Acidylphenyl)-based]amino}_2,3-dihydroindole small acid: Synthesis of -butyl ester 5-Amino-2,3-dihydro-1H-W哚-1-carboxylic acid tert-butyl ester substitution pair methoxy 128409 according to the procedure described in Preparation 1A and insignificantly changing -133 - 200836743 phenyl aniline to give 5-{[(2-nitrophenyl) benzyl]amino 2,3· dihydro-1 fluorene, small carboxylic acid tri-butyl ester (100%) : MS (ES+) m/z 384.2 (M + 1)· D· 5_{[(2·Aminophenyl) retino]aminodi 2,3_dihydro-1H-W 哚 small carboxylic acid third-butyl Synthesis of esters: as a procedure as described in Preparation 1B, and insignificant changes, using 5-{[(2-nitrophenyl) Substituted 2,3-dihydro-m-decanoic acid second-butyl ester to replace N-(4-methoxy-phenyl)_2-nitro-benzamide, obtaining 5_{[( 2_Aminophenyl)Werki]Aminodi 2,3-Dihydro-1H-W哚-1-carboxylic acid Third·Bycyl acetate (90%) : MS (ES+) m/z 354.2 (Μ + 1 Preparation of 5 2-Amino-N-(4-aminesulfonylphenyl)benzamide A 2 -nitro-N-(4-aminesulfonylphenyl)benzamide The synthesis was carried out according to the procedure as described in Preparation 1A, and the insignificant change was carried out, and p-methoxyaniline was replaced with p-aminobenzenesulfonamide, and purified by column chromatography to obtain 2-nitro-N. -(4-Aminosulfonylphenyl)benzamide (1% by weight) as a colorless solid: MS (ES+) m/z 322.2 (M + 1). Β· 2_amine·Ν-(4 -Aminosulfonylphenyl)benzamide The synthesis is carried out as described in Preparation 1B, and irrelevant changes are made using 2-nitro-N-(4-aminesulfonylphenyl) Benzalamine replaces N_(4) methoxy-phenyl&gt; 2-shidocylbenzene(tetra)amine, which is purified by column chromatography to give 2-aminona-aminosulfonylphenyl)benzamide (47%) ), as a colorless solid: MS (10) +) heart 292.2 (Μ + 1). Synthesis of 6 M[(2-aminophenyl)methyl]amino}benzoic acid oxime ester 128409 -134- 200836743 Α· 4-{[(2-nitrophenyl)methyl]amino}benzene Synthesis of formic acid methyl broth According to the procedure described in Preparation 1 ,, and irrelevant changes were made, and p-nonyloxyaniline was replaced with methyl 4-aminobenzoate to obtain 4_{[(2-nitrophenyl). Carbonyl]amino}methyl benzoate (90%): MS (ES+) m/z 301_1 (M + 1&gt;. 4-· 4-{[(2-aminophenyl)carbonyl]amino}benzoic acid Synthesis of the methyl ester According to the procedure described in Preparation 1 ,, and irrelevant changes were made, replacing ν_(4-methoxyl) with methyl 4-{[(2-Shidocylphenyl)-amino}benzoate -Phenyl)-2 - phenylbenzamide to give 4-{[(2-aminophenyl)methyl]amino)benzoic acid formazan (50%) : 1 H NMR (300 MHz, CD3 OD) 5 8·03 (d, J = 8.5 Ηζ, 2Η), 7.92 (s, 1Η), 7.65 (d, J = 8.5 Ηζ, 2Η), 7.46 (d, J = 7.9 Ηζ, 1Η) , 7.29-7.21 (m, 1H), 6.74-6.65 (m, 2H), 5.50 (br, 2H), 3.89 (s, 3H). Preparation 7 5-{[(2-Aminophenyl)]] Amino}-iH_吲嗓-i-carboxylic acid third Synthesis of butyl vinegar A. Synthesis of 3-nitro-1H-indole-1-carboxylic acid tert-butyl ester: If the procedure described in Preparation 4A is performed and the insignificant change is performed, 5-- Substituting nitro-1H-H丨哚 for 5-nitroporphyrin to give 5-nitroguanidine-1-carboxylic acid tert-butyl ester (98%) : 1H NMR (300 MHz, CDC13) 5 8.47 ( d, J = 2.0 Hz, 1H), 8.28-8.15 (m, 2H), 7_72 (d, J = 3·5 Hz, 1H), 6.70 (d, J = 3. 5)

Hz，1H)，1.67 (s，9H). B· 5-胺基哚小羧酸第三-丁酯之合成 知:知如製備1B中所述之程序，且施行無關緊要之改變， 使用5-硝基-1H-吲哚小羧酸第三-丁酯置換N_…甲氧基-笨 基）-2-硝基苯甲醯胺，並縮短反應時間至五分鐘，獲得孓胺 基-1H-吲哚小羧酸第三-丁酯（93%) : i η刪汉（3〇〇 MHz，CDCl3) 128409 -135 - 200836743 (5 7.90 (d, J = 7.3 Hz, 1H), 7.50 (d, J = 3.5 Hz, 1H), 6.81 (d, J = 2.3 Hz, 1H), 6.69 (dd, J = 8.4, 2.0 Hz, 1H), 6.38 (d, J = 3.8 Hz, 1H), 3.47 (s, 2H), 1.64 (s，9H). ’ C· 5_{[(2-硝基苯基）羰基】胺基HH_^哚小羧酸第三_丁酯之 合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用5-胺基-1H-蚓哚小羧酸第三-丁酯置換對_曱氧基苯胺， 獲付5·{[(2·碗基苯基）幾基]胺基卜ih-p?丨嗓-1-魏酸第三_丁酉旨 (61%) : 1H NMR (300 MHz，CDC13) 5 8.05 (d，J = 8.2 Ηζ，2Η)，7.94 (s， 1H)，7.79 (s，1H)，7.70-7.51 (m，4H)，7.27 (dd，7·50 (d，J = 1·8, 8.4 Hz， 1H)，6·52 (d，卜 3·5 Hz，1H)，1.65 (s，9H). D· 5-{【(2-胺基苯基）幾基】胺基卜ijj-巧丨嗓_1-敌酸第三-丁醋之 合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用5-{[(2-硝基苯基）幾基]胺基卜1H，哚-1-羧酸第三-丁 s旨置 換N-(4-甲氧基-苯基）-2-石肖基苯甲醯胺，並縮短反應時間至五 、 ' 分鐘，獲得5-{[(2·胺基苯基）羰基]胺基哚小羧酸第三_ 丁酯（85%) : iH NMR (300 MHz，CDC13) δ 8.08 (d，J = 8.8 Hz，1H)， 7.93 (d，J = 1.8 Hz，1H)，7.83 (s，1H)，7.57 (d，J = 3.8 Hz，1H)，7.48 (d，J =7·9 Hz，1H)，7.32-7.19 (m，2H)，6.74-6.65 (m，2H)，6.53 (d，J = 3.8 Hz5 1H)，5.49 (s，2H)，1.66 (s，9H). 製備8 (4-{[(2·胺基苯基）羰基]胺基}苯基）胺基曱酸第三-丁醋之合成 Α. (4-{[(2_硝基苯基）戴基】胺基}苯基）胺基甲酸第三-丁酯之 128409 -136- 200836743 合成 按照製備1A中所述之程序，且施行無關緊要之改變，使 用（4-胺基苯基）胺基甲酸第三-丁酯置換對-甲氧基苯胺，於 自醋酸乙酯與己烷再結晶後，獲得（4-{[(2-硝基苯基）獄基]胺 基}苯基）胺基甲酸第三-丁酯（66%) : MS (ES+) m/z 358.1 (Μ + 1). Β· (4-{丨(2-胺基苯基）羰基]胺基}苯基）胺基甲酸第三_ 丁酯之 合成 f / 按照如製備1Β中所述之程序，且施行無關緊要之改變， 使用（4-{[(2-硝基苯基豫基]胺基}苯基）胺基曱酸第三_丁酯置 換Ν-(4-甲氧基-苯基）_2_石肖基-苯甲醮胺，於自醋酸乙酯與己烧 再結晶後，獲得（4-{[(2·胺基苯基）魏基]胺基}苯基）胺基甲酸 第三-丁酯（52%) : 1 H NMR (300 MHz，DMSO-d6) 5 9.90 (s，1Η)，9.30 (s，1H)，7.66-7.54 (m，3H)，7.45-7.35 (m，2H)，7.20 (t，J = 8·2 Hz，1H)，6.75 (d，J = 8·2 Hz，1H)，6.59 (t，J = 7.3 Hz，1H)，6.33 (s，2H)，1.49 (s，9H); MS (ES+) m/z 328.1 (M + 1). 製備9 2-胺基-N-(4-漠苯基）苯甲醯胺之合成 Α· Ν-(4-澳苯基）-2-石肖基苯曱醯胺之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用4-溴基苯胺置換對-甲氧基苯胺，獲得溴苯基&gt;2-石肖 基苯甲醯胺（96%) : TLC (醋酸乙酯/己烷，1/1.5 v/v) Rf= 0.3. Β· 2-胺基·Ν-(4-溴苯基）苯甲醯胺之合成 於N-(4-溴苯基）-2-硝基苯甲醯胺（0.92克，2.88毫莫耳）在甲 醇（50毫升）中之經攪拌溶液内，在環境溫度下，添加氯化 128409 -137- 200836743 錫（II)二水合物（3·3克，14.4毫莫耳）。將混合物於環境溫度下 攪拌過夜，然後倒入水（150毫升）中。以醋酸乙酯（3 χ %毫 升）萃取此懸浮液。將合併之有機層以飽和碳酸鈉溶液與水 洗滌，以無水硫酸納脫水乾燥，及過濾。在真空中濃縮渡 液。自醋酸乙酿/己烷再結晶，獲得2-胺基_ν_(4_溴苯基）苯甲 醯胺（0.29 克 ’ 35%) ’ 為無色固體：iH NMR 卩〇〇 MHz，CDC13) (5 7.71 (s，1H)，7.48-7.40 (m，5H)，7.28-7.22 (m，1H)，6.74-6.67 (m，2H)， 5.48 (br5 2H). 製備10 2-胺基-N-(2-硫基-1H-笨并咪唑乂基）苯甲醯胺之合成 A· 2·硝基-N_(2-硫基-111_苯并咪唑_5_基）苯曱醯胺之合成 知：如製備1A中所述之程序，且施行無關緊要之改變， 使用5-胺基-1H-苯并咪唑-2-硫醇置換對·甲氧基苯胺，獲得2_ 硝基-Ν-(2·硫基-1H-苯并咪唑_5_基）苯甲醯胺（1〇〇%) : lH丽化 (300 MHz，DMSOd6) ά 12.55 (s，2H)，10.74 (s，1H)，8.18 (d，J = 7.9 Hz， 1Η)，7.95-7.87 (m，1H)，7.85-7.75 (m，3H)，7·33-7·25 (m，1H)，7·15 (d，J = 8.8 Hz，1H) ; MS (ES+) m/z 315.0 (M + 1). B· 2-胺基-N-(2-硫基-1H-苯并咪唑々基）苯甲醯胺之合成 知:知、如製備9B中所述之程序，且施行無關緊要之改變， 使用2-硝基-N_(2-硫基-1H-苯并咪唑_5_基）苯甲醯胺置換 溴笨基）-2-硝基-苯甲醯胺，獲得2_胺基硫基_1H-苯并咪 唾-5·基）笨甲 ϋ 胺（27%) : ^ NMR (300 MHz，CD3OD) 5 7.82 (s， 1H)，7.63 (dd，了 = 1.5, 8.2 Hz，1H)，7.36 (dd，I = 1.8, 8·2 Hz，1H)， 7.30-7.19 (m，2H)，6.82 (d，J = 8.2 Hz，1H)，6.73 (td，J = 1.2, 8.2 Hz，lH)· 128409 -138- 200836743 製備11 2-胺基-N-(2-酮基-2,3-二氫w苯并十坐各基）苯甲酿胺之合成 A· 6_胺基-1，3·苯并噚唑_2(3H)-酮之合成 按照如製備m中所述之程序，^施行無關緊要之改變， 使用6硝基苯并％唑_2(3H)_酮置換N_(4_甲氧基_苯基）_2_墙基 笨甲ik胺，獲得6-胺基]，3·苯并呤唑-2(3办酮（87%):丨H NMR (300 MHz, CD3 OD) (5 8.24 (d? J = 8.2 Hz? 1H)? 6.67 (d5 J = 1.8 Hz5 1H)? 6.56 (dd，J = 8.2, 2.0 Hz，1H). B· 硝基·&quot;义(2-酮基·2,3_二氫-1，3_苯并吟唑·6_基）苯甲醯胺之 合成 按照如製備1Α中所述之程序，且施行無關緊要之改變， 使用6-胺基-1，3-苯并嘮唑-2(3Η)-酮置換對-甲氧基苯胺，獲得 2-頌基·Ν-(2-酮基-2,3-二氫]，3-苯并嘮唑-6-基）苯甲醯胺（44%): NMR (300 MHz, CD3OD) 5 8.19-8.14 (m5 1H)? 7.85-7.78 (m? 1H)? 7.74-7.67 (m，3H)，7.31 (dd，J = 1.5, 8.2 Hz，1H)，7.08 (d，J = 8·5 Hz，1H)· C· 2-胺基-Ν·(2·酮基_2,3_二氫_1，3_苯并〃号嗅各基）苯甲醯胺之 合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用2-石肖基-N-(2-嗣基-2,3-一鐵* 苯弁p号唾-6-基）苯曱酸胺置 換N-(4-曱氧基-苯基）-2-石肖基苯甲醯胺，自醋酸乙g旨/己烧藉 再結晶獲得2-胺基-N-(2-S同基-2,3-二氮·1，3-苯并p号。坐各基）苯甲 醯胺（82%) : 1H NMR (300 MHz，DMSO-d6) δ 10.09 (s，1Η)，7.78 (d，J =1.8 Ηζ，1Η)5 7.64 (dd，J = 1·5, 7·9 Ηζ，1Η)，7.44 (dd，J = 8.5, 1.8 Ηζ， 1Η)，7·23 (t，J = 8.5, 1.5 Ηζ，1Η)，7.08 (d，J = 8.2 Ηζ，1Η)，6.78 (dd，J 二 128409 -139- 200836743 8.2, 〇·9 HZ，1H)，6·62 ⑽卜 7.9, 0.9 Hz, 1H)，6_36 (s，2H) 製備12 5.胺基苯基機基]胺基}_1H_苯并三唾·丨遵酸第三-丁酿之 合成 A· 5-硝基_1Η·苯并三唑小羧酸第三_丁酯之合成 按照如製備4Α中所述之程序，且施行無關緊要之改變， 使用5-破基苯并三。坐置換5_硝基⑼哚啉，自醋酸乙醋/己烧 藉再結晶獲得5-硝基-1Η-笨并三唑小羧酸第三_丁酯（26%): i η NMR (300 MHz, CDC13 ) 5 9.04-9.00 (m, iH), 8.52 (dd, J = 9.〇, 2.〇 Hz, 1H)5 8.22 (d，J = 9.0 Hz，1H)，1.76 (s，9H). B· 5-胺基-1H·苯并三唑小羧酸第三·丁酯之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用5-石肖基-1H-苯并三唆-1-羧酸第三-丁 g旨置換N-(4·甲氧基_ 苯基）-2-硝基苯甲酷胺’並縮短反應時間至二十分鐘，獲得 5-胺基-1H-苯并三唑小羧酸第三-丁酯（96%) : 1H NMR (3〇〇 MHz， CDC13) (5 7.78 (d，J = 8·8 Hz，1H)，7.14 (d，J = 2.3 Hz，1H)，6·76 (dd，J = 8.8, 2.0 Hz，1H)，4.25 (s，2H)，1.69 (s，9H)· C. 5-{[(2_硝基苯基）叛基]胺基}_1H·苯并三唑-1-羧酸第三-丁 酯之合成 按照如製備1A中所述之程序’且施行無關緊要之改變， 使用5·胺基·1Η·苯并三唑小魏酸第三-丁醋置換對-甲氧基苯 胺，於管柱層析純化後，獲得5-爪2-硝基苯基）幾基]胺基卜1Η· 苯并三唑小羧酸第三-丁酯（42%): ihnmr(300 MHz，CDC13)占 8.88 (s，1H)，8_69 (s，1H)，7·97 (d，J = 8·5 Hz，1H)，7·89 (d，J = 8 5 Hz， -140- 128409 200836743 1H)，7.66-7.56 (m，2H)，7.53-7.46 (m，1Η)，7·38 (dd，J = 8.8, 1·5 Hz，1H)， 1.71 (s，9H)· D· 5-{[(2_胺基苯基）魏基]胺基}_1H-苯并三啥_i_缓酸第三丁 酯之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用5-{[(2-石肖基本基）幾基]胺基}_1]3_苯并三唾-1-魏酸第三-丁 酉旨置換N-(4-曱氧基-苯基）-2-頌基苯曱醯胺，於自醋酸乙酯/ 己烷再結晶後，獲得5·{[(2-胺基苯基）魏基]胺基}_1H-苯并三 唑小羧酸第三-丁酯（56%) : iH NMR (300 MHz，CDC13) 5 8.66 (s， 1H)，8·14-7·98 (m，2H)，7.55-7.38 (m，2H)，7.32-7.22 (m，1H)，6.79-6.66 (m，2H)，5.56 (br，2H)，1.76 (s，9H). 製備13 5-{[(2-胺基苯基）幾基]胺基}-lH-吲唾-1-羧酸第三-丁酯之合成 A· 5-硝基丨嗤小致酸第三-丁酯之合成 按照如製備4A中所述之程序，且施行無關緊要之改變， 使用5-硝基蚓唑置換5-硝基吲哚啉，獲得5·硝基-1H-啕唑-1-羧酸第三-丁酯（99%) : 4 NMR (300 MHz，CDC13) 3 8.70-8.67 (m， 1H)，8.44-8.38 (m，1H)，8.35-8.29 (m，2H)，1.73 (s，9H)· B· 5-胺基丨嗤小魏酸第三丁醋之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用5-硝基-1H-W唑小羧酸第三-丁酯置換N-(4-甲氧基-苯 基）-2-確基苯甲醯胺，獲得5-胺基-1H-4卜坐-1-魏酸第三-丁酯 (88%) ： !H NMR (300 MHz, CDC13) δ 7.96-7.82 (m? 2Η)? 6.90-6.78 (m? 2Η)，3.80 (s，2Η)，1·63 (s，9Η). 128409 -141 - 200836743 C· 5-{[(2-石肖基本基）艘基]胺基丨嗅-1-致酸第三一丁醋之 合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用5-胺基-1H-啕唑小羧酸第三·丁酯置換對·甲氧基苯胺， 獲得5-{[(2_确基苯基）魏基]胺基}-1Η-4卜坐-1-緩酸第三-丁酯 (81%) ： NMR (300 MHz, CD3OD) δ 8.37-8.33 (m? 2Η)? 8.24 (d5 J = 8.2 Hz，1H)，8.16 (d，J = 9·1 Hz，1H)，7.93-7.85 (m，1H)，7.82-7.71 (m， 3H)，1.76 (s，9H)· D· 5-{[(2-胺基苯基）幾基]胺基卜1H_啕唑小羧酸第三·丁酯之 合成Hz, 1H), 1.67 (s, 9H). Synthesis of B- 5-aminoindole carboxylic acid tert-butyl ester: Know the procedure described in Preparation 1B, and perform irrelevant changes, use 5 -Nitro-1H-indole small carboxylic acid tert-butyl ester replaces N_...methoxy-styl)-2-nitrobenzamide, and shortens the reaction time to five minutes to obtain amidino-1H - hydrazine small carboxylic acid tert-butyl ester (93%): i η 汉 汉 (3〇〇MHz, CDCl3) 128409 -135 - 200836743 (5 7.90 (d, J = 7.3 Hz, 1H), 7.50 (d , J = 3.5 Hz, 1H), 6.81 (d, J = 2.3 Hz, 1H), 6.69 (dd, J = 8.4, 2.0 Hz, 1H), 6.38 (d, J = 3.8 Hz, 1H), 3.47 (s , 2H), 1.64 (s, 9H). 'C·5_{[(2-nitrophenyl)carbonyl]amino HH_^哚carboxylic acid tert-butyl ester is synthesized as described in Preparation 1A Procedure, and the implementation of the insignificant change, the use of 5-amino-1H-indole small carboxylic acid tert-butyl ester to replace p-nonyloxyaniline, paid 5·{[(2·Banylphenyl) Amino group ih-p?丨嗓-1-weilic acid third_丁酉(61%) : 1H NMR (300 MHz, CDC13) 5 8.05 (d, J = 8.2 Ηζ, 2Η), 7.94 (s , 1H), 7.79 (s, 1H), 7.70-7.51 (m, 4H) , 7.27 (dd, 7·50 (d, J = 1·8, 8.4 Hz, 1H), 6.52 (d, Bu 3·5 Hz, 1H), 1.65 (s, 9H). D· 5-{ [(2-Aminophenyl) aryl] amide ijj- 丨嗓 - _1 - diacid acid third - butyl vinegar synthesis according to the procedure as described in Preparation 1B, and the implementation of irrelevant changes, use 5-{[(2-nitrophenyl)methyl]aminopyr 1H, indole-1-carboxylic acid, tert-butyr, substituted N-(4-methoxy-phenyl)-2-stone benzyl Methionine, and shorten the reaction time to five, 'minutes, to obtain 5-{[(2·aminophenyl)carbonyl]aminoguanidine carboxylic acid tert-butyl ester (85%): iH NMR (300 MHz , CDC13) δ 8.08 (d, J = 8.8 Hz, 1H), 7.93 (d, J = 1.8 Hz, 1H), 7.83 (s, 1H), 7.57 (d, J = 3.8 Hz, 1H), 7.48 (d , J =7·9 Hz,1H),7.32-7.19 (m,2H),6.74-6.65 (m,2H),6.53 (d,J = 3.8 Hz5 1H), 5.49 (s,2H),1.66 (s , 9H). Preparation of 8 (4-{[(2)aminophenyl)carbonyl]amino}phenyl)amino decanoic acid tert-butyl vinegar synthesis Α. (4-{[(2_nitro) Phenyl)diyl]amino}phenyl)aminocarbamic acid tert-butyl ester 128409 -136- 200836743 Synthesis according to Preparation 1A Procedure, and insignificant change, using p-methoxyaniline (4-aminophenyl)carbamic acid tert-butyl ester, after recrystallization from ethyl acetate and hexane, (4) -{[(2-Nitrophenyl)phenyl]amino}phenyl)carbamic acid tert-butyl ester (66%) : MS (ES+) m/z 358.1 (Μ + 1). Β· ( Synthesis of 4-{丨(2-aminophenyl)carbonyl]amino}phenyl)carbamic acid tert-butyl ester f / according to the procedure as described in Preparation 1Β, and applying irrelevant changes, use (4-{[(2-Nitrophenyl)]amino}phenyl)amino decanoic acid tert-butyl ester substituted Ν-(4-methoxy-phenyl)_2_shishenyl-benzonitrile The amine, after recrystallization from ethyl acetate and hexane, gave (4-{[(2.amino)phenyl)- yl)amino}phenyl) carbamic acid as the third-butyl ester (52%): 1 H NMR (300 MHz, DMSO-d6) 5 9.90 (s, 1 Η), 9.30 (s, 1H), 7.66-7.54 (m, 3H), 7.45-7.35 (m, 2H), 7.20 (t, J = 8·2 Hz, 1H), 6.75 (d, J = 8·2 Hz, 1H), 6.59 (t, J = 7.3 Hz, 1H), 6.33 (s, 2H), 1.49 (s, 9H); MS ( ES+) m/z 328.1 (M + 1). Preparation 9 2-Amino-N-(4 Synthesis of benzyl phenyl decylamine 合成·(4-Anophenyl)-2-stone sulfenylamine was synthesized according to the procedure as described in Preparation 1A, and the inconsequential changes were used. Substituting 4-bromoaniline for p-methoxyaniline to give bromophenyl &lt;2-stone succinylbenzamide (96%): TLC (ethyl acetate/hexane, 1/1.5 v/v) Rf = 0.3 . Synthesis of 2-amino-2-indole-(4-bromophenyl)benzamide as N-(4-bromophenyl)-2-nitrobenzamide (0.92 g, 2.88 mmol) In a stirred solution of methanol (50 ml), chlorinated 128409-137-200836743 tin(II) dihydrate (3.3 g, 14.4 mmol) was added at ambient temperature. The mixture was stirred at ambient temperature overnight then poured into water (150 mL). This suspension was extracted with ethyl acetate (3 χ % mL). The combined organic layers were washed with a saturated aqueous solution of sodium carbonate and water, dried over anhydrous sodium sulfate, and filtered. Concentrate the liquid in a vacuum. Recrystallization from acetic acid / hexane to give 2-amino _ν_(4-bromophenyl)benzamide (0.29 g '35%) 'as colorless solid: iH NMR 卩〇〇MHz, CDC13) 5 7.71 (s, 1H), 7.48-7.40 (m, 5H), 7.28-7.22 (m, 1H), 6.74-6.67 (m, 2H), 5.48 (br5 2H). Preparation 10 2-Amino-N- Synthesis of (2-thio-1H-benzoimidazolyl)benzamide A Synthesis of 2·Nitro-N_(2-thio-111_benzimidazole-5-yl)benzamide It is known that, as in the procedure described in Preparation 1A, and irrelevant changes are made, 5-amino-1H-benzimidazole-2-thiol is substituted for p-methoxyaniline to obtain 2_nitro-indole-( 2·thio-1H-benzimidazole _5-yl)benzamide (1〇〇%) : lH 丽化(300 MHz, DMSOd6) ά 12.55 (s, 2H), 10.74 (s, 1H), 8.18 (d, J = 7.9 Hz, 1Η), 7.95-7.87 (m, 1H), 7.85-7.75 (m, 3H), 7·33-7·25 (m, 1H), 7·15 (d, J = 8.8 Hz,1H) ; MS (ES+) m/z 315.0 (M + 1). Synthesis of B. 2-Amino-N-(2-thio-1H-benzimidazolyl)benzamide Know: know, as prepared in the procedure described in 9B, and perform irrelevant changes, using 2-nitrate -N_(2-thio-1H-benzimidazole-5-yl)benzamide to replace bromophenyl)-2-nitro-benzamide to obtain 2-aminothio-1H-benzo Amino (5%): ^ NMR (300 MHz, CD3OD) 5 7.82 (s, 1H), 7.63 (dd, = 1.5, 8.2 Hz, 1H), 7.36 (dd, I = 1.8, 8·2 Hz, 1H), 7.30-7.19 (m, 2H), 6.82 (d, J = 8.2 Hz, 1H), 6.73 (td, J = 1.2, 8.2 Hz, lH)· 128409 -138 - 200836743 Preparation of 11 2-Amino-N-(2-keto-2,3-dihydro-w-benzoyl)-Benzylamine Synthesis A·6_Amino-1,3·Benzene The synthesis of carbazole-2(3H)-one was carried out according to the procedure described in Preparation m, and the insignificant change was carried out, and N_(4_methoxy) was replaced with 6-nitrobenzoxazole-2(3H)-one. Base _phenyl)_2_wall-based amide, obtaining 6-amino],3·benzoxazole-2 (3 ketone (87%): 丨H NMR (300 MHz, CD3 OD) (5 8.24 (d? J = 8.2 Hz? 1H)? 6.67 (d5 J = 1.8 Hz5 1H)? 6.56 (dd, J = 8.2, 2.0 Hz, 1H). B· Nitro·&quot; (2-keto) Synthesis of 2,3_dihydro-1,3-benzoxazole·6-yl)benzamide according to the procedure as described in Preparation 1Α, and irrelevant If desired, the p-methoxyaniline is replaced with 6-amino-1,3-benzoxazol-2(3Η)-one to give 2-mercapto-indolyl-(2-keto-2,3) -Dihydro],3-benzoxazol-6-yl)benzamide (44%): NMR (300 MHz, CD3OD) 5 8.19-8.14 (m5 1H)? 7.85-7.78 (m? 1H)? 7.74-7.67 (m,3H), 7.31 (dd, J = 1.5, 8.2 Hz, 1H), 7.08 (d, J = 8·5 Hz, 1H)· C· 2-Amino-Ν·(2·ketone Synthesis of benzyl-2,3-dihydro-1,3_benzoxanthene benzylideneamine according to the procedure as described in Preparation 1B, and irrelevant changes were made using 2-stone Schottky-N -(2-mercapto-2,3-iron*benzoquinone p-sal-6-yl)benzoic acid amine replacing N-(4-decyloxy-phenyl)-2-stone benzyl carbamide 2-Amino-N-(2-S-yl-2,3-diaza·1,3-benzop) was obtained by recrystallization from acetic acid. Benzimidamide (82%): 1H NMR (300 MHz, DMSO-d6) δ 10.09 (s, 1 Η), 7.78 (d, J = 1.8 Ηζ, 1 Η) 5 7.64 (dd, J = 1 ·5, 7·9 Ηζ, 1Η), 7.44 (dd, J = 8.5, 1.8 Ηζ, 1 Η), 7·23 (t, J = 8.5, 1.5 Ηζ, 1 Η), 7.08 (d, J = 8.2 Ηζ, 1Η), 6.78 (dd, J 2 128409 -139- 200836743 8.2, 〇·9 HZ, 1H), 6·62 (10) 7.9, 0.9 Hz, 1H), 6_36 (s, 2H) Preparation 12 5. Aminobenzene Base group] amine group}_1H_benzotrisole·supplement acid third-butyl synthesis A· 5-nitro-1Η·benzotriazole small carboxylic acid synthesis of third butyl ester according to preparation The procedure described in 4Α, and the implementation of the insignificant changes, the use of 5-aminobenzotriene. Separation of 5_nitro(9) porphyrin, recrystallization from ethyl acetate / hexane to obtain 5-nitro-1 oxime-stuppyrazole small carboxylic acid tert-butyl ester (26%): i η NMR (300 MHz, CDC13) 5 9.04-9.00 (m, iH), 8.52 (dd, J = 9.〇, 2.〇Hz, 1H)5 8.22 (d, J = 9.0 Hz, 1H), 1.76 (s, 9H) . Synthesis of B. 5-Amino-1H-benzotriazole Small Carboxylic Acid Tri-Butyl Ester According to the procedure described in Preparation 1B, and using an insignificant change, 5-stone Schottky-1H-Benzene is used. Triterpene-1-carboxylic acid third-butyryl is intended to replace N-(4.methoxy-phenyl)-2-nitrobenzamide and shorten the reaction time to twenty minutes to obtain 5-amino group -1H-benzotriazole carboxylic acid tert-butyl ester (96%) : 1H NMR (3 〇〇 MHz, CDC13) (5 7.78 (d, J = 8·8 Hz, 1H), 7.14 (d, J = 2.3 Hz, 1H), 6.76 (dd, J = 8.8, 2.0 Hz, 1H), 4.25 (s, 2H), 1.69 (s, 9H) · C. 5-{[(2_nitrobenzene) Synthesis of alkyl}_1H·benzotriazole-1-carboxylic acid tert-butyl ester according to the procedure described in Preparation 1A and using an insignificant change, using 5·amine·1Η · benzotriazole weiwei acid third-butyric acid replacement p-methoxy Amine, after purification by column chromatography, gave 5-claw 2-nitrophenyl) sylamino] carbazyl benzotriazole carboxylic acid tert-butyl ester (42%): ihnmr (300 MHz) , CDC13) occupies 8.88 (s, 1H), 8_69 (s, 1H), 7·97 (d, J = 8·5 Hz, 1H), 7·89 (d, J = 8 5 Hz, -140- 128409 200836743 1H), 7.66-7.56 (m, 2H), 7.53-7.46 (m, 1 Η), 7·38 (dd, J = 8.8, 1.5 Hz, 1H), 1.71 (s, 9H)· D· 5 Synthesis of -{[(2-aminophenyl)weil]amino}_1H-benzotriazine_i_sodium butyl sulphate according to the procedure as described in Preparation 1B, and irrelevant changes were performed , using 5-{[(2-Shisha basic) alkyl]amino}_1]3_benzotris-l-propionic acid third-butyryl substituted N-(4-decyloxy-phenyl颂-2-mercaptobenzamine, after recrystallization from ethyl acetate / hexane, 5·{[(2-aminophenyl)weiki]amino}_1H-benzotriazole carboxylate Acidic third-butyl ester (56%): iH NMR (300 MHz, CDC13) 5 8.66 (s, 1H), 8·14-7·98 (m, 2H), 7.55-7.38 (m, 2H), 7.32 -7.22 (m, 1H), 6.79-6.66 (m, 2H), 5.56 (br, 2H), 1.76 (s, 9H). Preparation 13 5-{[(2-Aminophenyl) Synthesis of alkyl}-lH-indole-1-carboxylic acid tert-butyl ester A. Synthesis of 5-nitroindole small acid tris-butyl ester according to the procedure as described in Preparation 4A, And the insignificant change was made, using 5-nitrocarbazole to replace 5-nitroporphyrin to obtain 5·nitro-1H-indazole-1-carboxylic acid tert-butyl ester (99%): 4 NMR (300 MHz, CDC13) 3 8.70-8.67 (m, 1H), 8.44 - 8.38 (m, 1H), 8.35-8.29 (m, 2H), 1.73 (s, 9H) · B · 5-amine Synthesis of the third vinegar of succinic acid according to the procedure as described in Preparation 1B, and the insignificant change was carried out, and N-(4-A was replaced with 5-nitro-1H-Wazole small carboxylic acid tert-butyl ester. Oxy-phenyl)-2-decylbenzamide to give 5-amino-1H-4b-l-weilic acid tert-butyl ester (88%) : !H NMR (300 MHz, CDC13 δ 7.96-7.82 (m? 2Η)? 6.90-6.78 (m? 2Η), 3.80 (s, 2Η), 1·63 (s, 9Η). 128409 -141 - 200836743 C· 5-{[(2- Synthesis of alkaloids, amines, scent-1, and acid, the first butyl vinegar. According to the procedure described in Preparation 1A, and the insignificant changes were made, 5-amino-1H-oxime was used. Thiazole small carboxylic acid third butyl ester substitution pair Methoxyaniline, 5-{[(2-decylphenyl))-yl]amino}-1Η-4b-s--1-carboxylic acid tert-butyl ester (81%): NMR (300 MHz, CD3OD) δ 8.37-8.33 (m? 2Η)? 8.24 (d5 J = 8.2 Hz, 1H), 8.16 (d, J = 9·1 Hz, 1H), 7.93-7.85 (m, 1H), 7.82-7.71 ( Synthesis of m, 3H), 1.76 (s, 9H)·D· 5-{[(2-Aminophenyl)methyl]aminopyr 1H-carbazole small carboxylic acid

按照如製備1B中所述之程序，且施行無關緊要之改變， 使用5-{[(2-硝基苯基）魏基]胺基唑小羧酸第三_丁酯置 換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，獲得5-{[(2-胺基苯基） 羰基]胺基}-1Η-啕唑-1-羧酸第三丁酯（95%): 1H NMR (300 MHz， CDC13) 5 8.22-8.01 (m，4H)，7.53-7.45 (m，2H)，7.28-7.19 (m，1H)， 6.74-6.63 (m，2H)，1.70 (s，9H)· 製備14 2-甲基-4H-3，1-苯并口号p井-4-酮之合成 將鄰胺基苯甲酸（1·8克，13·1毫莫耳）與醋酸酐（2〇毫升， 過量）混合，並於13〇°C下回流3小時。在高真空下移除過量 醋酸酐，而得2-甲基-4H-3，1-苯并啰畊斗酮（2.1克，100%)，為 油性產物：TLC (醋酸乙酯/己烷，1/2 v/v) Rf= 0.3. 製備15 2-戊基-4H-3，1-苯并^号ρ井-4·酮之合成 128409 -142- 200836743 將鄰胺基苯甲酸（1·0克，7.3毫莫耳）與己酸酐（4毫升，14.3 毫莫耳）混合，並於13〇°C下回流3小時。在高真空下移除過 量己酸酐，而得2-戊基-4Η·3，1-苯并嘮畊斗酮（1.58克，100%)， 為油性產物：TLC (醋酸乙酯/己烷，1/3 v/v) Rf= 0.7· 製備16 (2_{[(2-胺基苯基豫基]胺基}苯基）胺基甲酸第三·丁 g旨之合成 A· (2-硝基苯基）胺基甲酸第三-丁醋之合成 按照如製備4A中所述之程序，且施行無關緊要之改變， 使用2-硝基苯胺置換5_硝基啕哚啉，獲得（2-硝基苯基）胺基甲 酸第三-丁酯（44%) : 1 H NMR (300 MHz，CDC13) 5 9.64 (s，1H)，8.53 (dd，J = 8.5, 1.2 Hz，1H)，8· 16 (dd，J = 8.5, 1.8 Hz，1H)，7.62-7.54 (m，1H)， 7.06 (td，J = 8.5, 1·2 Hz，1H)，1.52 (s，9H). B· (2-胺基苯基）胺基甲酸第三-丁酯之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用（2_硝基苯基）胺基甲酸第三-丁酯置換N_(4-甲氧基-苯 基墙基苯甲醯胺，獲得（2-胺基苯基）胺基甲酸第三-丁酯 (87%):NMR (300 MHz，CDC13) δ 7.30-7.20 (m，1H)，7.02-6.93 (m， 1H)，6.83-6.69 (m，2H)，6·28 (bi*，1H)，3.46 (br，2H)，1.49 (s，9H)· C· (2-{[(2·硝基苯基）擬基]胺基}苯基）胺基甲酸第三·丁酯之 合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用（2-胺基苯基）胺基甲酸第三-丁酯置換對_甲氧基苯胺， 獲得（2-{[(2-硝基苯基）魏基]胺基}苯基）胺基曱酸第三_丁酉旨 (82%) ： 1H NMR (300 MHz, CDC13) 5 8.66 (s? 1H)? 8.06 (d3 J = 8.2 Hz, 128409 •143- 200836743 1Η)，7.71-7.54 (m5 4H)，7.37-7.28 (m，2H)，7.22-7.14 (m，2H)，6.86 (s，1H)， 1.43 (s，9H). D. (2-{[(2_胺基苯基）羰基]胺基}苯基）胺基甲酸第三-丁酯之 合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用（2-{[(2-硝基苯基）羰基]胺基}苯基）胺基甲酸第三-丁酯置 換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，獲得（2-{[(2-胺基苯基） 羰基]胺基}苯基）胺基甲酸第三-丁酯（94%) ·· 4 NMR (300 MHz， CDC13) 8.84 (s，1H)，7.64 (dd，J = 7.6, 1.8 Hz，1H)，7.55 (dd，J = 8.2, 1.2 Hz，1H)，7.30-7.10 (m，4H)，6·77 (s，1H)，6.71-6.61 (m，2H)，5·69 (s， 2H)，1.48 (s，9H). 製備17 (5-{[(2-胺基苯基）羰基]胺基}吡啶-2-基）胺基甲酸第三-丁酯之 合成 A. (5-頌基p比咬-2-基）胺基曱酸第三-丁醋之合成Displace N-(4- using 5-{[(2-nitrophenyl)weiry]aminoazole carboxylic acid tert-butyl ester according to the procedure as described in Preparation 1B and subject to insignificant changes Methoxy-phenyl)-2-nitrobenzamide, obtaining 5-{[(2-aminophenyl)carbonyl]amino}-1Η-indazole-1-carboxylic acid tert-butyl ester ( 95%): 1H NMR (300 MHz, CDC13) 5 8.22-8.01 (m, 4H), 7.53-7.45 (m, 2H), 7.28-7.19 (m, 1H), 6.74-6.63 (m, 2H), 1.70 (s, 9H)· Preparation 14 Synthesis of 2-methyl-4H-3,1-benzo- s-p-p--4-one Anthranilic benzoic acid (1.8 g, 13.1 mmol) and Acetic anhydride (2 liters, excess) was mixed and refluxed at 13 ° C for 3 hours. Excess acetic anhydride was removed under high vacuum to give 2-methyl-4H-3,1-benzoindole (2.1 g, 100%) as an oily product: TLC (ethyl acetate/hexanes, 1/2 v/v) Rf=0.3. Preparation of 15-2-pentyl-4H-3,1-benzox^ ρ Well-4·one Synthesis 128409-142- 200836743 o-Aminobenzoic acid (1· 0 g, 7.3 mmoles, mixed with hexanoic anhydride (4 mL, 14.3 mmol) and refluxed at 13 ° C for 3 hours. Excess hexanoic anhydride was removed under high vacuum to give 2-pentyl-4 Η3,1-benzoxanone (1.58 g, 100%) as an oily product: TLC (ethyl acetate/hexanes, 1/3 v/v) Rf= 0.7· Preparation 16 (2_{[(2-Aminophenyl)]amino}phenyl)aminocarboxylic acid III·丁克的合成A· (2-Nitrate Synthesis of phenyl-aminocarbamic acid tert-butyl vinegar According to the procedure as described in Preparation 4A, and irrelevant changes were made, and 5-nitroaniline was replaced with 2-nitroaniline to obtain (2- Nitrophenyl) carbamic acid tert-butyl ester (44%): 1 H NMR (300 MHz, CDC13) 5 9.64 (s, 1H), 8.53 (dd, J = 8.5, 1.2 Hz, 1H), 8 · 16 (dd, J = 8.5, 1.8 Hz, 1H), 7.62 - 7.54 (m, 1H), 7.06 (td, J = 8.5, 1 · 2 Hz, 1H), 1.52 (s, 9H). B· ( Synthesis of 2-aminophenyl)carbamic acid tert-butyl ester according to the procedure as described in Preparation 1B, and insignificantly changing, using (2-nitrophenyl)aminocarboxylic acid tert-butyl Ester replacement of N_(4-methoxy-phenyl-wall-benzamide to give (2-aminophenyl)carbamic acid tert-butyl ester (87%): NMR (300 MHz, CDC13) δ 7 . 30-7.20 (m, 1H), 7.02-6.93 (m, 1H), 6.83-6.69 (m, 2H), 6.28 (bi*, 1H), 3.46 (br, 2H), 1.49 (s, 9H) · The synthesis of C·(2-{[(2.nitrophenyl))]amino}phenyl)aminocarbamic acid tert-butyl ester according to the procedure as described in Preparation 1A, and the implementation is irrelevant Alternatively, the p-methoxyaniline is replaced with a (3-aminophenyl)carbamic acid tert-butyl ester to obtain (2-{[(2-nitrophenyl)wei)]amino}phenyl) Amino decanoic acid third _ 酉 酉 (82%): 1H NMR (300 MHz, CDC13) 5 8.66 (s? 1H)? 8.06 (d3 J = 8.2 Hz, 128409 • 143-200836743 1Η), 7.71-7.54 ( M5 4H), 7.37-7.28 (m, 2H), 7.22-7.14 (m, 2H), 6.86 (s, 1H), 1.43 (s, 9H). D. (2-{[(2_Aminophenyl) Synthesis of carbonyl]amino}phenyl)aminocarbamic acid tert-butyl ester according to the procedure as described in Preparation 1B, and irrelevant changes were made using (2-{[(2-nitrophenyl)) Replacement of N-(4-methoxy-phenyl)-2-nitrobenzamide with a carbonyl]amino}phenyl)aminocarbamic acid tert-butyl ester to give (2-{[(2-amino) Phenyl) carbonyl]amino}phenyl)aminocarboxylic acid third - Ester (94%) ·· 4 NMR (300 MHz, CDC13) 8.84 (s, 1H), 7.64 (dd, J = 7.6, 1.8 Hz, 1H), 7.55 (dd, J = 8.2, 1.2 Hz, 1H), 7.30-7.10 (m,4H),6·77 (s,1H),6.71-6.61 (m,2H),5·69 (s, 2H), 1.48 (s,9H). Preparation 17 (5-{[ Synthesis of (2-aminophenyl)carbonyl]amino}pyridin-2-yl)carbamic acid tert-butyl ester A. (5-fluorenyl p-biti-2-yl) amino decanoic acid - Synthesis of vinegar

按照如製備4A中所述之程序，且施行無關緊要之改變， 使用5-确基咐咬-2-胺置換5-硝基4丨嗓琳’獲得（5-确基π比σ定_2_ 基）胺基甲酸第三-丁醋（46%) : 1H NMR (300 MHz，CDC13) δ 9.51 (s，1H)，6·21 (d，J = 2·9 Hz，1H)，8·26 (dd，J = 9·4, 2.6 Hz，1H)，8·22 (d，J =9·4 Hz，1H), 1_58 (s，9H). B. (5-胺基吡啶-2-基）胺基甲酸第三-丁酯之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用（5-硝基吡啶-2-基）胺基甲酸第三-丁酯置換N-(4-甲氧基_ 苯基）-2-硝基苯甲醯胺，獲得（5-胺基吡啶-2-基）胺基曱酸第三 128409 -144- 200836743 -丁酯（89%): 1H NMR (300 MHz, CDC13) (5 8·41 (s，1Η)，7·80 (d，J = 2.9 Hz，1H)，7.73 (d，J = 8.8 Hz，1H)，7.02 (dd，J = 8.8, 2·9 Hz，1H)，3.46 (s， 2H)，1·50 (s，9H). C· (5-{[(2_硝基苯基）幾基]胺基p比啶-2-基）胺基甲酸第三-丁 酯之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用（5-胺基吡啶-2-基）胺基甲酸第三-丁酯置換對-甲氧基苯 胺，獲得（5-{[(2-硝基苯基）魏基]胺基}吡啶-2-基）胺基甲酸第 三-丁酯（89%) ·· 4 NMR (300 MHz，CDC13) ά 8.42 (s，1H)，8.14-8.08 (m，1Η)，8.01-7.91 (m，2Η)，7.76-7.68 (m，2Η)，7.66-7.57 (m，3Η)，1·57 (s， 9H). D· (5-{[(2-胺基苯基）羰基】胺基}吡啶_2_基）胺基甲酸第三·丁 酯之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用（5-{[(2-硝基苯基）幾基]胺基㈣啶-2-基）胺基曱酸第三-丁 酯置換N-(4-甲氧基-苯基）-2-頌基苯曱醯胺，獲得（5-{[(2_胺基 苯基）羰基]胺基}吡啶-2-基）胺基甲酸第三-丁酯（95%): 1H NMR (300 MHz，CDC13) (5 8.44-8.39 (m，1Η)，7.94 (d，J = 1.5 Ηζ，1Η)，7·78 (d， J = 10·8 Hz，2H)，7·48-7·41 (m，1H)，7.24 (td，J = 7.9, 1·5 Hz，1H)， 6.73-6.65 (m，2H)，1.51 (s，9H). 製備18 (4-{[(2-胺基苯基）幾基]胺基}苄基）胺基甲酸第三-丁 g旨之合成 Α· (4·{[(2·硝基苯基）羰基】胺基}爷基）胺基甲酸第三-丁酯之 合成 128409 -145- 200836743 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用（4-胺基苄基）胺基曱酸第三-丁酯置換對-甲氧基苯胺， 獲得（4-{[(2-硝基苯基）幾基]胺基}宇基）胺基甲酸第三-丁酯 (47%) : 1H NMR (300 MHz，CDC13) 5 8.11 (d，J = 8·2 Ηζ，1Η)，7.76-7.68 (m，1Η)，7.66-7.49 (m，5H)，7.31-7.24 (m，2H)，4_84 (br，1H)，4·27 (d，J = 5.5 Hz，2H)，1.44 (s，9H). B· (4-{[(2_胺基苯基）幾基】胺基}爷基）胺基甲酸第三_丁酯之 合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用（4_{[(2-硝基苯基）幾基]胺基}爷基）胺基甲酸第三叮酯置 換N-(4-甲氧基-苯基）-2_硝基-苯甲醯胺，獲得（4-{[(2_胺基苯基） 羰基]胺基}苄基）胺基甲酸第三-丁酯（68%) : 1 H NMR (3〇〇 MHz， CDC13) (5 7.74 (s，1H)，7.55-7.41 (m，3H)，7·31-7·20 (m，3H)，6.75-6.65 (m，2H)，5.48 (br，2H)，4.82 (br，1H)，4.27 (d，J = 5·8 Hz，2H)，1·44 (s，9H). 製備19 [4-{[(2-胺基苯基）魏基]胺基卜2-(三氟甲基）苯基]胺基甲酸第 三丁 S旨之合成 A· [4-破基-2_(三氣甲基）苯基】胺基曱酸第三_丁醋之合成 按照如製備4A中所述之程序，且施行無關緊要之改變， 使用4-確基-2-(三氟甲基）苯胺置換5_硝基吲哚啉，獲得[4_頌 基_2_(三氟甲基）苯基]胺基甲酸第三·丁酯（27%):丨Η （3〇〇 MHz? CDC13) 5 8.53 (d5 J = 9.3 Hz? 1H)? 8.43 (d? J = 2.3 Hz5 1H)? 8.38 (dd，J = 9.1，2,3 Hz，1H)，7.34 (s，1H)，1.54 (s，9H). B· [4-胺基_2-(三氟甲基）苯基】胺基f酸第三旨之合成 128409 -146- 200836743 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用[4_硝基冬(三氟甲基）苯基]胺基甲酸第三_丁酯置換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，獲得[4-胺基-2-(三氟甲基）苯 基]胺基甲酸第三-丁酯（84%) : 1H NMR (300 MHz，CDC13)占 7.64 (d，J = 8.2 Hz，1H)，6.91-6.78 (m，2H)，6.39 (s，1H)，1.48 (s，9H). c· [4_{[(2-硝基苯基）幾基】胺基}-2_(三氟甲基）苯基]胺基甲酸 第三-丁酿之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用[4-胺基-2-(三氟甲基）苯基]胺基甲酸第三-丁酯置換對· 甲氧基苯胺，獲得[4-{[(2-硝基苯基）羰基]胺基}-2-(三氟甲基） 苯基]胺基甲酸第三丁酯（75%) : 4 NMR (300 MHz，CDC13) 5 8·57 (s，1H)，8·01 (d，J = 8·2 Hz，1H)，7.77-7.60 (m，3H)，7.57-7.40 (m， 3H)，6·66 (s，1H)，1.42 (s，9H)· D· [4-{[(2-胺基苯基）羰基]胺基}_2-(三氟甲基）苯基]胺基甲酸 第三-丁醋之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用[4-{[(2-硝基苯基）幾基]胺基}-2-(三氟甲基）苯基]胺基甲 酸第三-丁酯置換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，獲得 [4-{[(2-胺基苯基）羰基]胺基}-2-(三氟甲基）苯基]胺基甲酸第 三-丁酯（79%) : MS (ES+) m/z 396.3 (M + 1). 製備20 [4-{[(2-胺基苯基）魏基]胺基}-3-(三氟甲基）苯基]胺基甲酸第 三-丁酯之合成 A.【4-硝基-3-(三氟甲基）苯基]胺基甲酸第三-丁酯之合成 128409 -147- 200836743 按照如製備4A中所述之程序，且施行無關緊要之改變， 使用4-硝基-3-(三氟甲基）苯胺置換5_硝基啕哚啉，獲得屮硝 基_3-(三氟甲基）苯基]胺基甲酸第三-丁酯（81%) : i H NMR (3〇〇 MHz，CDC13) 5 7·95 (d，J = 9.1 Hz，1H)，7.84 (d，J = 2·3 Hz，1H)，7·70 (dd，J = 9.1，2,3 Hz，1H)，6·89 (s，1H)，1·52 (s, 9H). B· [4·胺基各(三氟甲基）苯基】胺基甲酸第三-丁醋之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用[4-硝基-3-(三氟甲基）苯基]胺基甲酸第三_丁酯置換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，獲得[4_胺基_3_(三氟甲基）苯 基]胺基甲酸第三-丁酯（66%) : 1H NMR (300 MHz，CDC13) 5 7Λ2 (s，1H)，7.35-7.24 (m，1H)，6·76_6·64 (m，1H)，6.29 (br，1H)，1.49 (s，9H). C· [4-{[(2-硝基苯基）羰基】胺基卜3_(三氟甲基）苯基】胺基甲酸 第三-丁醋之合成 按照如製備1A中所述之程序，且施行無關緊要之改變， 使用[4-胺基_3-(三氟甲基）苯基]胺基甲酸第三·丁酯置換對_ 甲氧基苯胺，獲得[4-{[(2,基苯基）羰基]胺基}-3-(三氟甲基） 苯基]胺基甲酸第三-丁酯（16%) : 1 H NMR (300 MHz，CDC13) 5 8·13 (d，J = 7.9 Hz，1H)，7.98 (d，J = 8·8 Hz，1H)，7.85 (s，1H)，7.78-7.69 (m，1H)，7.68-7.56 (m，3H)，7.40 (dd，J = 8.5，1.8 Hz，1H)，6.79 (s，1H)， 1.49 (s, 9H). D· [4·{[(2_胺基苯基）羰基】胺基}_3_(三氟甲基）苯基】胺基甲酸 第三-丁 S旨之合成 按照如製備1B中所述之程序，且施行無關緊要之改變， 使用[4-{[(2-硝基苯基）魏基]胺基}-3_(三氟甲基）苯基]胺基甲 128409 -148- 200836743 酸第三-丁酯置換N-(4-甲氧基-苯基）-2-硝基苯曱醯胺，獲得 [4-{[(2-胺基苯基）幾基]胺基卜3-(三氟甲基）苯基]胺基甲酸第 三-丁酯（72%): 1H NMR (300 MHz, CDC13) 6 8.09 (d，J = 8.8 Hz，1H)， 7·98 (s，1H)，7.82 (d，J = 2.0 Hz，1H)，7.46-7.38 (m，2H)，7.30-7.21 (m， 1H)，6.76-6.62 (m，3H)，1.51 (s，9H). 製備21 (4-{[(2-胺基苯基）幾基]胺基}環己基)胺基甲酸第三-丁 g旨之合成 Α· 0H[(2_硝基苯基）幾棊]胺基}環己基）胺基甲酸第三_丁酯 之合成 於氯化2-硝基苯甲醯（0.38克，2.05毫莫耳）在二氯甲烷（5 毫升）中之溶液内，在環境溫度下，慢慢添加4_胺基環己基 胺基甲酸第三-丁酯（0.43克，2.00毫莫耳）與三乙胺（〇·31毫升， 2.20毫莫耳）。將混合物於環境溫度下攪拌十六小時，接著 添加二氣甲烷（100毫升）。將混合物以1Μ檸檬酸溶液、飽和 碳酸鈉溶液及鹽水洗滌，以無水硫酸鈉脫水乾燥，及過濾。 在真空中濃縮濾液’獲得（4-{[(2-硝基苯基）幾基]胺基}環己 基）胺基甲酸第二-丁酯（0.30克，41%)，為白色固體：娜（ES+) m/z 364.2 (Μ + 1). Β· 0Η[(2-胺基苯基）幾基]胺基}環己基）胺基甲酸第三·丁醋 之合成 使(4-{[(2-梢基苯基）羰基]胺基}環己基）胺基甲酸第三-丁酯 (0.300克，0.826毫莫耳）在甲醇（20毫升）中之溶液，於i大氣 壓下，使用1〇%Pd/C(〇.1〇〇克）作為觸媒，在環境溫度下接受 氫化作用十六小時。經過矽藻土過濾混合物，並使濾液蒸 128409 •149· 200836743 發至乾酒。使殘留物接受管柱層析（在己烷中之50%醋酸乙 醋）’獲得（4-{[(2-胺基苯基）幾基]胺基}環己基）胺基甲酸第三 -丁酯（0.100 克，36%)，為無色固體：MS (ES+) m/z 334·2 (M + 1)· 製備22 2-丁基-4Η-嘧吩并[3,2-d][l，3]呤畊-4-酮之合成 A· 3_(戊醯基胺基）p塞吩_2_羧酸甲酯之合成 於3-胺基嘧吩-2-羧酸甲酯（3.93克，25毫莫耳）在二氯甲烷 (20毫升）中之溶液内，在〇艺下逐滴添加二異丙基乙胺（5 23 毫升，30毫莫耳）與氣化戊醯（3 03毫升，25·5毫莫耳）。將反 應混合物於環境溫度下攪拌十六小時，並添加二氯甲烧 (100毫升）。藉由1Ν鹽酸溶液、飽和碳酸氫鈉及鹽水洗滌混 合物。使有機層以無水硫酸鈉脫水乾燥，及過濾。使濾液 在真空中濃縮至乾涸，獲得3-(戊酸基胺基）ρ塞吩_2_魏酸甲酯 (6.00 克，99%)，為黃色油性產物：1 η NMR (300 MHz，CDC13) 5 8.12 (d，J = 5·7 Hz，1H)，7·44 (d，J = 5.4 Hz，1H)，3.86 (s，3H)，2.43 (t， J = 7.5 Hz，2H)，1.75-1.65 (m，2H)，1.45-1.30 (m，2H)，0.92 (t，J = 7.5 Hz， 3H) ； MS (ES+) m/z 242.1 (M + 1). B· 3-(戊醯基胺基）噻吩：羧酸之合成 於3-(戊醯基胺基）p塞吩-2-羧酸甲酯（6.00克，25毫莫耳）在甲 醇（50毫升）中之溶液内，添加氫氧化鈉溶液（2N，ΐ2·5毫升， 25毫莫耳）。將反應混合物於環境溫度下攪拌16小時。使混 合物在真空中濃縮至乾涸。使殘留物溶於水中，並添加濃 鹽酸，直到pH &lt; 2為止。以醋酸乙酯（3 X 50毫升）萃取混合 物。？辰合併之有機層’獲得3-(戊酿基胺基）p塞吩幾酸（5 65 128409 -150- 200836743According to the procedure as described in Preparation 4A, and the insignificant change is made, 5-quinone-2-amine is substituted for 5-nitro-4-indolyl (5-determined π ratio σ定_2_ Amino carboxylic acid, third-butyl vinegar (46%): 1H NMR (300 MHz, CDC13) δ 9.51 (s, 1H), 6·21 (d, J = 2·9 Hz, 1H), 8.26 (dd, J = 9·4, 2.6 Hz, 1H), 8·22 (d, J = 9·4 Hz, 1H), 1_58 (s, 9H). B. (5-Aminopyridin-2-yl) Synthesis of tert-butyl carbamic acid according to the procedure as described in Preparation 1B, and irrelevant changes were made using a (3-nitropyridin-2-yl)carbamic acid tert-butyl ester in place of N -(4-methoxy-phenyl)-2-nitrobenzamide to give (5-aminopyridin-2-yl)amine decanoic acid #128409-144-200836743-butyl ester (89% ): 1H NMR (300 MHz, CDC13) (5 8·41 (s, 1Η), 7·80 (d, J = 2.9 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.02 (dd , J = 8.8, 2·9 Hz, 1H), 3.46 (s, 2H), 1·50 (s, 9H). C·(5-{[(2_Nitrophenyl))amino]p Synthesis of the pyridyl-2-yl)carbamic acid tert-butyl ester according to the procedure as described in Preparation 1A, and Insignificant change, using p-methoxyaniline with (3-aminopyridin-2-yl)carbamic acid tert-butyl ester to obtain (5-{[(2-nitrophenyl)weil] Amino-pyridin-2-yl)carbamic acid tert-butyl ester (89%) ·· 4 NMR (300 MHz, CDC13) ά 8.42 (s, 1H), 8.14-8.08 (m, 1 Η), 8.01 7.91 (m, 2Η), 7.76-7.68 (m, 2Η), 7.66-7.57 (m, 3Η), 1.57 (s, 9H). D· (5-{[(2-Aminophenyl)carbonyl) Synthesis of Amino}pyridine-2-yl)carbamic acid tert-butyl ester according to the procedure as described in Preparation 1B, and irrelevant changes were made using (5-{[(2-nitrophenyl) Amino-(tetra)pyridin-2-yl)amino decanoic acid tert-butyl ester is substituted for N-(4-methoxy-phenyl)-2-mercaptobenzamine to obtain (5-{ [(2-aminophenyl)carbonyl]amino}pyridin-2-yl)carbamic acid tert-butyl ester (95%): 1H NMR (300 MHz, CDC13) (5 8.44-8.39 (m, 1 Η ), 7.94 (d, J = 1.5 Ηζ, 1 Η), 7·78 (d, J = 10·8 Hz, 2H), 7·48-7·41 (m, 1H), 7.24 (td, J = 7.9) , 1·5 Hz, 1H), 6.73-6.65 (m, 2H), 1.51 (s, 9H). Preparation 18 (4-{[(2-aminophenyl) Amino]benzyl}benzyl)aminocarboxylic acid, the third-butyr, the synthesis of ruthenium (4·{[(2.nitrophenyl)carbonyl]amino] aryl) aminocarboxylic acid third - Synthesis of Butyl Ester 128409 -145- 200836743 Displacement of p-methoxy with (4-aminobenzyl)amine decanoic acid tert-butyl ester according to the procedure described in Preparation 1A, and with irrelevant changes Aniline, (4-{[(2-nitrophenyl)methyl]amino}ylidene) carboxylic acid tert-butyl ester (47%) : 1H NMR (300 MHz, CDC13) 5 8.11 (d , J = 8·2 Ηζ, 1Η), 7.76-7.68 (m, 1Η), 7.66-7.49 (m, 5H), 7.31-7.24 (m, 2H), 4_84 (br, 1H), 4·27 (d , J = 5.5 Hz, 2H), 1.44 (s, 9H). B·(4-{[(2_Aminophenyl))ylamino]amino}yl)carbamic acid III-butyl ester synthesis Substituting (4_{[(2-nitrophenyl)methyl]amino} yl) carbamic acid tert- phthalate for N-(in accordance with the procedure as described in Preparation 1B, and carrying out irrelevant changes) 4-methoxy-phenyl)-2-nitro-benzamide, obtaining (4-{[(2-aminophenyl)carbonyl]amino}benzyl)carbamic acid tert-butyl ester (68%) : 1 H NMR (3〇 〇MHz, CDC13) (5 7.74 (s, 1H), 7.55-7.41 (m, 3H), 7·31-7·20 (m, 3H), 6.75-6.65 (m, 2H), 5.48 (br, 2H) ), 4.82 (br, 1H), 4.27 (d, J = 5·8 Hz, 2H), 1·44 (s, 9H). Preparation 19 [4-{[(2-Aminophenyl)]] Aminobutyr 2-(trifluoromethyl)phenyl]aminocarbamic acid tert-butyl S-synthesis A·[4-基基-2_(trimethylmethyl)phenyl]amino decanoic acid Synthesis of vinegar According to the procedure as described in Preparation 4A, and irrelevant changes were made, and 5-nitrophenyl porphyrin was replaced with 4-decyl-2-(trifluoromethyl)aniline to obtain [4_fluorenyl). _2_(Trifluoromethyl)phenyl]carbamic acid tert-butyl ester (27%): 丨Η (3〇〇MHz? CDC13) 5 8.53 (d5 J = 9.3 Hz? 1H)? 8.43 (d? J = 2.3 Hz5 1H)? 8.38 (dd, J = 9.1, 2, 3 Hz, 1H), 7.34 (s, 1H), 1.54 (s, 9H). B· [4-Amino-2-(trifluoro Methyl)phenyl]aminol acid The synthesis of the third purpose 128409-146-200836743 According to the procedure as described in Preparation 1B, and with irrelevant changes, [4_nitro-m-(trifluoromethyl) Phenyl]aminocarboxylic acid tert-butyl ester replaces N-(4-methoxy-phenyl)-2-nitrate Benzoylamine afforded [4-amino-2-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester (84%): 1H NMR (300 MHz, CDC13). 7.64 (d, J = 8.2 Hz, 1H), 6.91-6.78 (m, 2H), 6.39 (s, 1H), 1.48 (s, 9H). c. [4_{[(2-Nitrophenyl))amino] Synthesis of -2_(trifluoromethyl)phenyl]carbamic acid as a third-butanization procedure according to the procedure as described in Preparation 1A, and with irrelevant changes, using [4-amino-2-(trifluoro) Methyl)phenyl]carbamic acid tert-butyl ester substituted p-methoxyaniline to give [4-{[(2-nitrophenyl)carbonyl]amino}-2-(trifluoromethyl) Phenyl] carbamic acid tert-butyl ester (75%): 4 NMR (300 MHz, CDC13) 5 8·57 (s, 1H), 8·01 (d, J = 8·2 Hz, 1H), 7.77 -7.60 (m,3H), 7.57-7.40 (m, 3H),6·66 (s,1H), 1.42 (s,9H)·D· [4-{[(2-Aminophenyl)carbonyl] Synthesis of amino}_2-(trifluoromethyl)phenyl]carbamic acid tert-butyl vinegar According to the procedure as described in Preparation 1B, and irrelevant changes were made using [4-{[(2- Nitrophenyl)methyl]amino}-2-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester Replacing N-(4-methoxy-phenyl)-2-nitrobenzamide to give [4-{[(2-aminophenyl)carbonyl]amino}-2-(trifluoromethyl) Phenyl] carbamic acid tert-butyl ester (79%): MS (ES+) m/z 396.3 (M + 1). Preparation 20 [4-{[(2-aminophenyl)] Synthesis of tert-butyl ester of -3-(trifluoromethyl)phenyl]carbamic acid A. [4-nitro-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl Synthesis of the ester 128409 -147- 200836743 According to the procedure as described in Preparation 4A, and subject to irrelevant changes, 5-nitro-3-(trifluoromethyl)aniline was substituted for 5-nitroporphyrin.第三Nitro-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester (81%) : i H NMR (3 〇〇 MHz, CDC13) 5 7·95 (d, J = 9.1 Hz ,1H),7.84 (d,J = 2·3 Hz,1H),7·70 (dd,J = 9.1,2,3 Hz,1H),6·89 (s,1H),1·52 (s , 9H). B. [4. Amino-(trifluoromethyl)phenyl]-aminocarboxylic acid, the third-butyl vinegar is synthesized according to the procedure as described in Preparation 1B, and the irrelevant changes are used, [ 4-nitro-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester replaces N-(4-methoxy -Phenyl)-2-nitrobenzamide to give [4-amino]-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester (66%): 1H NMR (300 MHz, CDC13) 5 7Λ2 (s,1H),7.35-7.24 (m,1H),6·76_6·64 (m,1H), 6.29 (br,1H),1.49 (s,9H). C· [4-{ Synthesis of [(2-nitrophenyl)carbonyl]aminodibu 3_(trifluoromethyl)phenyl]aminocarbamic acid tert-butyl vinegar according to the procedure as described in Preparation 1A, and irrelevant changes were performed Substituting [4-amino-3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester for p-methoxyaniline to obtain [4-{[(2,ylphenyl)carbonyl] Amino--3-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester (16%): 1 H NMR (300 MHz, CDC13) 5 8·13 (d, J = 7.9 Hz, 1H ), 7.98 (d, J = 8·8 Hz, 1H), 7.85 (s, 1H), 7.78-7.69 (m, 1H), 7.68-7.56 (m, 3H), 7.40 (dd, J = 8.5, 1.8) Hz,1H),6.79 (s,1H), 1.49 (s, 9H). D· [4·{[(2-aminophenyl)carbonyl]amino}_3_(trifluoromethyl)phenyl]amine The synthesis of the carboxylic acid third-butane S is carried out according to the procedure as described in Preparation 1B, and the irrelevant modification is carried out. , using [4-{[(2-nitrophenyl)wei)]amino}-3-(trifluoromethyl)phenyl]aminomethyl 128409-148-200836743 acid tert-butyl ester replacement N-( 4-methoxy-phenyl)-2-nitrobenzamine to give [4-{[(2-aminophenyl))amino) 3-(trifluoromethyl)phenyl] Tert-butyl carbamic acid (72%): 1H NMR (300 MHz, CDC13) 6 8.09 (d, J = 8.8 Hz, 1H), 7·98 (s, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.46-7.38 (m, 2H), 7.30-7.21 (m, 1H), 6.76-6.62 (m, 3H), 1.51 (s, 9H). Preparation 21 (4-{[(2-amine) Alkyl phenyl) benzyl]amino}cyclohexyl) carbamic acid tert-butyl ketone Α·0H[(2-nitrophenyl) oxime]amino}cyclohexyl) carbamic acid Synthesis of butyl ester in a solution of 2-nitrobenzhydrazide chloride (0.38 g, 2.05 mmol) in dichloromethane (5 ml), slowly adding 4_amino ring at ambient temperature Tri-butyl hexylaminocarbamate (0.43 g, 2.00 mmol) and triethylamine (〇·31 mL, 2.20 mmol). The mixture was stirred at ambient temperature for sixteen hours then di-methane (100 mL) was added. The mixture was washed with 1 citric acid solution, saturated sodium carbonate solution and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give (4-{[(2-nitrophenyl)-yl]amino}cyclohexyl)carbamic acid as the second-butyl ester (0.30 g, 41%) as white solid: Na (ES+) m/z 364.2 (Μ + 1). Β·0Η[(2-Aminophenyl)alkyl]amino}cyclohexyl)carbamic acid III·butyl vinegar synthesis (4-{[ (2-Phenylphenyl)carbonyl]amino}cyclohexyl)carbamic acid tert-butyl ester (0.300 g, 0.826 mmol) in methanol (20 mL), i at atmospheric pressure, using 1 〇%Pd/C (〇.1 gram) was used as a catalyst to accept hydrogenation at ambient temperature for sixteen hours. The mixture was filtered through celite and the filtrate was evaporated to dryness. The residue was subjected to column chromatography (50% ethyl acetate in hexane) to obtain (4-{[(2-aminophenyl))]amino}cyclohexyl) carbamic acid - Butyl ester (0.100 g, 36%) as colorless solid: MS (ES+) m/z 334·2 (M + 1) · Preparation 22 2-butyl-4-indole-[5,2-d][ l,3] Synthesis of sorghum-4-ketone A·3_(pentamethyleneamino)p-cephene-2-carboxylic acid methyl ester synthesized in methyl 3-aminopyridin-2-carboxylate (3.93 Gram, 25 mM) diisopropylethylamine (5 23 ml, 30 mmol) and gasified amylose (3 ml) in a solution of dichloromethane (20 ml) 03 ml, 25. 5 millimoles). The reaction mixture was stirred at ambient temperature for sixteen hours and dichloromethane (100 mL) was added. The mixture was washed with a 1 HCl solution, saturated sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo to give &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&&&& ) 5 8.12 (d, J = 5·7 Hz, 1H), 7·44 (d, J = 5.4 Hz, 1H), 3.86 (s, 3H), 2.43 (t, J = 7.5 Hz, 2H), 1.75 -1.65 (m, 2H), 1.45-1.30 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H); MS (ES+) m/z 242.1 (M + 1). B· 3-( Alkyl)thiophene: a carboxylic acid synthesized in a solution of methyl 3-(pentamethyleneamino)p-cephen-2-carboxylate (6.00 g, 25 mmol) in methanol (50 mL) Add sodium hydroxide solution (2N, ΐ2·5 ml, 25 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The mixture was concentrated to dryness in vacuo. The residue was dissolved in water and concentrated hydrochloric acid was added until pH &lt; The mixture was extracted with ethyl acetate (3 X 50 mL). ? The organic layer of the combination was obtained to obtain 3-(pentylamino)p-secenoic acid (5 65 128409 -150- 200836743

克，99%)，為淡黃色固體：1 η NMR (300 MHz，CDC13) 610.02 (s， 1H)，8·17 (d，J = 8.4 Hz，1H)，7.56 (d，J = 8·4 Hz，1H)，2.45 (t，J = 7.5 Hz， 2H)，1.65-1.77 (m，2H)，1.44-1.36 (m，2H)，0.95 (t，J = 7.5 Hz, 3H) ; MS (ES-) m/z 226.0 (M-l). C· 2-丁基_4H_嘍吩并[3,2-d][l，3]嘮畊-4-酮之合成 使3-(戊醯基胺基 &gt;塞吩冬羧酸（5.65克，24·8毫莫耳）與醋酸 酐（20宅升）之混合物回流2小時。使反應混合物在真空中濃 縮至乾涸，獲得2-丁基-4H-嘧吩并[3,2-d][l，3]哼畔冰_ (5.20克， 99%)，為淡黃色油：MS (ES+) m/z 210.1 (M + 1). 製備23 2-丁基_4H-嘧吩并[2,3-d][l，3]哼畊-4-酮之合成 A· 2-(戊醯基胺基）p塞吩-3-羧酸甲酯之合成 按照如製備22A中所述之程序，且施行無關緊要之改變， 使用2_胺基遠吩-3-魏酸甲酯置換3_胺基喧吩-2-魏酸酯，獲得 2-(戊醯基胺基）噻吩-3-羧酸甲酯（90%)，為淡黃色液體·· MS (ES+) m/z 242.1 (Μ + 1). Β· 2_(戊醯基胺基）〃塞吩_3·叛酸之合成 按照如製備22Β中所述之程序，且施行無關緊要之改變， 使用2-(戊醯基胺基）雀吩-3·羧酸甲酯置換3-(戊醯基胺基）遠 吩-2-羧酸甲酯，獲得2-(戊醯基胺基）嘧吩-3-羧酸（90%)，為淡 褐色固體·· 4 NMR (300 MHz，CDC13) 5 10.76 (s，1Η)，7.24 (d，J = 8.7 Hz，1H)，6.75 (d，J = 8·7 Hz，1H)，2.51 (t，J = 7·5 Hz，2H)，1·8(Μ·67 (m，2H)，1.49-1.37 (m，2H)，0.95 (t，J = 7.5 Hz，3H) ; MS (ES-) m/z 226.1 (M-l). 128409 -151 - 200836743 C· 2-丁基_411-〃塞吩并[2,3-(1】[1，3】崎〃井-4-酮之合成 私:&amp;如製備22C中所述之程序’且施行無關緊要之改變， 使用2-(戊醯基胺基）遠吩_3_羧酸置換3_(戊醯基胺基）遠吩冬 羧酸，獲得2-丁基-4H-嘧吩并p，3-d][l，3]喝畊冰酮（75%)，為淡 褐色液體：MS (ES+) m/z 210.1 (M + 1). 製備24 2-丁基-7-甲基-4H-嘧吩并[3,2-d][l，3]呤畊斗酮之合成 A. ‘甲基-3-(戊醯基胺基）p塞吩_2_叛酸甲酯之合成 私：知、如製備22A中所述之程序’且施行無關緊要之改變， 使用3_胺基冰甲基嘧吩冬羧酸甲酯置換3_胺基嘧吩冬竣酸 酯’獲得4-甲基-3·(戊醯基胺基 &gt;塞吩_2_羧酸甲酯（8〇〇/〇)，為淡 黃色液體：MS (ES+) m/z 256.1 (M + 1). Β· 4-甲基-3-(戊醯基胺基）〃塞吩_2_叛酸之合成 按知、如製備22Β中所述之程序，且施行無關緊要之改變， 使用4-甲基-3-(戊醯基胺基）遠吩_2_羧酸甲酯置換3_(戊醯基胺 基）遽吩-2-羧酸甲酯，獲得4_甲基-3-(戊醯基胺基 &gt;塞吩丨羧酸 (65%)，為淡黃色固體：iHNMR (300 MHz，CDC13) δ 8.62 (s，1H) 2.43 (t，J = 7·5 Ηζ，2Η)，2.19 (s，3Η)，1_77，1·65 (m，2Η)，1_49-1·34 (m，2Η)， 0·95 (t，J = 7.5 Ηζ5 3Η) ; MS (ES-) m/z 240.1 (M-l)· C· 2-丁基_7_甲基_411〜塞吩并[3,2-(1][1，3】十井-4-酮之合成 按照如製備22C中所述之程序，且施行無關緊要之改變， 使用4-甲基-3-(戊醯基胺基 &gt;塞吩丨羧酸置換3_(戊醯基胺基） 嘧吩-2·羧酸，獲得2-丁基-7-甲基-4H-噻吩并[3,2-d][l，3]噚畊斗 酮（99%)，為淡黃色液體：Ms (ES+) ▲ 224 1 + ^· 128409 -152· 200836743 製備25 4-{[(2-胺基苯基機基]胺基}六氫吨n定-μ魏酸第三-丁酉旨之合成 A· 4-{[(2_石肖基苯基）幾基】胺基}六氫p比咬小叛酸第三-丁醋 之合成 按照如製備21A中所述之程序，且施行無關緊要之改變， 使用4-胺基六氫吡啶-1-羧酸第三-丁酯置換4_胺基環己基胺 基甲酸第三-丁酯，獲得4_{[(2-硝基苯基）魏基]胺基}六氫吡啶 -1·羧酸第三丁酯（93%)，為淡黃色液體：1h NMR (300 MHz， CDC13) 5 8·05 (d，J = 8.1 Hz，1H)，7.70-7.45 (m，3H)，5.88-5.70 (m，1H)， 4.18-3.97 (m? 3H)? 2.95-2.83 (m? 2H), 2.10-1.98 (m, 2H)? 1.45-1.39 (m, 11H) ； MS (ES+) m/z 350.1 (M + 1). B· 4-{[(2·胺基苯基）幾基]胺基}六氫？比咬小叛酸第三-丁酯 之合成 按照如製備21B中所述之程序，且施行無關緊要之改變， 使用4-{[(2-硝基苯基）幾基]胺基}六氫吡唆小羧酸第三-丁酯 置換（4-{[(2-確基苯基）幾基]胺基}環己基）胺基甲酸第三-丁 酯，獲得4-{[(2-胺基苯基）幾基]胺基}六氫吡啶羧酸第三_ 丁酯（94%)，為淡黃色固體：MS (ES+) m/z 320.2 (Μ + 1). 製備26 3-(4-嗎福琳-4-基苯基）-2_苯基_2,3-二氫4唑琳-4(1Η)-_之合成 Α· N-(4-嗎福啉-4-基苯基）-2-硝基苯甲醯胺之合成 按照如製備21A中所述之程序，且施行無關緊要之改變， 使用4-嗎福啉基苯胺置換4-胺基環己基胺基甲酸第三叮酯， 獲得N-(4-嗎福啉-4-基苯基)-2-石肖基苯甲醯胺（47%)，為無色固 128409 -153- 200836743 體：1H NMR (300 MHz，丙酮啕）占 9 51 (s，1H)，8 〇6 ⑽，j = 7 8, 〇 6Gram, 99%), as pale yellow solid: 1 η NMR (300 MHz, CDC13) 610.02 (s, 1H), 8·17 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8·4 Hz, 1H), 2.45 (t, J = 7.5 Hz, 2H), 1.65-1.77 (m, 2H), 1.44-1.36 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H); MS (ES -) m/z 226.0 (Ml). C· 2-Butyl-4H_喽[3,2-d][l,3]唠耕-4-ketone Synthesis 3-(pentamidineamine A mixture of cetyl carboxylic acid (5.65 g, 24.8 mmol) and acetic anhydride (20 liters) was refluxed for 2 hours. The reaction mixture was concentrated in vacuo to dryness to afford 2-butyl-4H. -Mimido[3,2-d][l,3] 哼 冰 _ (5.20 g, 99%), as pale yellow oil: MS (ES+) m/z 210.1 (M + 1). Preparation 23 2 Synthesis of butyl-4H-sulfonio[2,3-d][l,3]indole-4-one A·2-(pentamethyleneamino)p-cephen-3-carboxylic acid methyl ester The synthesis was carried out according to the procedure as described in Preparation 22A, and the insignificant change was carried out, and the 2-aminophene-2-carboxylate was replaced with 2-amino- farophen-3-methyl acid methyl ester to obtain 2- (Pentylmethylamino)thiophene-3-carboxylic acid methyl ester (90%) as a pale yellow liquid · MS (ES+) m/z 242.1 (Μ + 1). Synthesis of 2_(pentamethylene amino) thiophene _3· tacrotic acid According to the procedure described in Preparation 22, and irrelevant changes were made, 2-(pentamethylene amide) stilbene-3 was used. Methyl carboxylate was substituted for methyl 3-(pentamethyleneamino) far phen-2-carboxylate to give 2-(pentenylamino)pyrimen-3-carboxylic acid (90%) as a light brown solid ·· 4 NMR (300 MHz, CDC13) 5 10.76 (s, 1Η), 7.24 (d, J = 8.7 Hz, 1H), 6.75 (d, J = 8·7 Hz, 1H), 2.51 (t, J = 7·5 Hz, 2H), 1·8 (Μ·67 (m, 2H), 1.49-1.37 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H); MS (ES-) m/z 226.1 (Ml). 128409 -151 - 200836743 C· 2-Butyl-411-〃 吩 并 [2,3-(1][1,3] The synthesis of the ketone-4-ketone: & Prepare the procedure described in 22C and perform an insignificant change by replacing 2-(pentenylamino) far-tertiary carboxylic acid with 2-(pentamethyleneamino) far-fibrate-3-carboxylic acid to obtain 2- Butyl-4H-sulfono-p,3-d][l,3] icy ketone (75%), light brown liquid: MS (ES+) m/z 210.1 (M + 1). Preparation 24 2 Synthesis of butyl-7-methyl-4H-sulfeno[3,2-d][l,3]indole ketone A. 'Methyl-3-( Synthesis of pentamidine-based p-phene-2-a-t-acid methyl ester: Knowing, as described in Preparation 22A' and performing irrelevant changes, using 3-amino-amylmethylsulfonamide Methyl ester substitution of 3_amino sulfonium phthalate 'obtained 4-methyl-3·(pentamethoxyamino)&gt;cephene-2-carboxylic acid methyl ester (8〇〇/〇), light Yellow liquid: MS (ES+) m/z 256.1 (M + 1). Β· 4-methyl-3-(pentamethylene amide) 〃 吩 _2 _ _ _ _ _ _ _ _ _ _ _ 叛 叛The procedure described, and insignificantly changing, replacing 3-(pentenylamino) porphin-2- with 4-methyl-3-(pentamethyleneamino) far phen-2-carboxylic acid methyl ester Methyl carboxylate to give 4-methyl-3-(pentamethyleneamine)&gt; cetin carboxylic acid (65%) as pale yellow solid: iHNMR (300 MHz, CDC13) δ 8.62 (s, 1H) 2.43 (t, J = 7·5 Ηζ, 2Η), 2.19 (s, 3Η), 1_77, 1·65 (m, 2Η), 1_49-1·34 (m, 2Η), 0·95 (t, J = 7.5 Ηζ5 3Η) ; MS (ES-) m/z 240.1 (Ml)· C· 2-butyl_7_methyl_411~seno[3,2-(1][1,3]10 Synthesis of well-4-ketone according to the procedure as described in Preparation 22C, and the implementation is irrelevant To be changed, 4-(3-pentenylamino)&gt; thiophene carboxylic acid was substituted for 3-(pentenylamino) sulfenophene-2-carboxylic acid to obtain 2-butyl-7- Methyl-4H-thieno[3,2-d][l,3]indole (99%), pale yellow liquid: Ms (ES+) ▲ 224 1 + ^· 128409 -152· 200836743 Preparation 25 4-{[(2-Aminophenyl)]amino}hexahydro ton n-di-weilic acid third-butyl hydrazine synthesis A· 4-{[(2_石肖基phenyl) ylamine Synthesis of hexahydro-p-small-small-stoichiic acid-small vinegar according to the procedure as described in Preparation 21A, and irrelevant changes were made using 4-aminopiperidine-1-carboxylic acid third- Butyl ester was substituted for the third-butyl ester of 4-aminocyclohexylaminocarbamate to obtain 4_{[(2-nitrophenyl)weil]amino}hexahydropyridine-1·carboxylic acid tert-butyl ester (93) %), in pale yellow liquid: 1h NMR (300 MHz, CDC13) 5 8·05 (d, J = 8.1 Hz, 1H), 7.70-7.45 (m, 3H), 5.88-5.70 (m, 1H), 4.18 -3.97 (m? 3H)? 2.95-2.83 (m? 2H), 2.10-1.98 (m, 2H)? 1.45-1.39 (m, 11H) ; MS (ES+) m/z 350.1 (M + 1). B · 4-{[(2·Aminophenyl)alkyl]amino}hexahydro? Synthesis of the third-butyl ester of the small acid-repellent acid according to the procedure as described in Preparation 21B, and the inconsequential change was carried out, using 4-{[(2-nitrophenyl)methyl]amino}hexahydro Dissociation of (3-{[(2-decylphenyl))]amino}cyclohexyl)carbamic acid tert-butyl ester with pyridinium carboxylic acid tert-butyl ester to give 4-{[(2- Aminophenyl) benzyl]amino}hexahydropyridinecarboxylic acid tert-butyl ester (94%) as a pale yellow solid: MS (ES+) m/z 320.2 ( Μ + 1). Preparation 26 3-( Synthesis of 4-norfosyl-4-ylphenyl)-2-phenylene-2,3-dihydrotetrazolium-4(1Η)--Α·N-(4-morpholin-4-yl Synthesis of Phenyl)-2-nitrobenzimidamide According to the procedure as described in Preparation 21A, and irrelevant changes were made, and 4-aminocyclohexylaminocarbamic acid was replaced with 4-morpholinoaniline. Triterpene ester, N-(4-morpholine-4-ylphenyl)-2-stone benzyl carbamide (47%) was obtained as colorless solid 128409-153-200836743 体:1H NMR (300 MHz, acetone啕) accounted for 9 51 (s, 1H), 8 〇 6 (10), j = 7 8, 〇 6

Hz，1H)，7.84-7.67 (m，3H)，7.61 (d，J =： 9·0 Hz，2H)，6.94 (d，J = 9·0 Hz， 2H)，3.76 (t，J = 4.8 Hz，4H)，3.09 (t，J = 4.8 Hz，4H); MS (ES+) m/z 328.3 (M + 1). B· 2_胺基·Ν-(4-嗎福琳-4-基苯基）苯曱醯胺之合成 按照製備21B中所述之程序，且施行無關緊要之改變，使 用N-(4-嗎福啉-4-基苯基&gt;2-硝基苯曱醯胺置換（4_{[(2_硝基苯 基）獄基]胺基}環己基）胺基甲酸第三_丁酯，獲得2-胺基-N-(4_ 嗎福琳-4-基苯基）苯甲酸胺（59%)，為灰色固體：1 η NMR (300 MHz，CD3OD) (5 9·77 (s，1Η)，7.57-7.49 (m，3Η)，7.14 (ddd，J = 7.8, 7.8, 1·2 Hz，1H)，3.88 (d, J = 9.0 Hz，2H)，6.70 (dd，J = 9.1，0·9 Hz，1H)，6.53 (ddd，J = 7.8, 7.8, 1.2 Hz，1H)，3.70 (t，J = 4·5 Hz，4H)，3.02 (t，J = 4.5 Hz， 4H) ； MS (ES+) m/z 320.2 (M + 23). C· 3-(4-嗎福琳_4-基苯基）·2_苯基_2,3-二氫〃奎唑淋_4(1H)_酮之 合成 於2-胺基-Ν·(4-嗎福啉-4-基苯基）苯甲醯胺（〇·2〇克，0.67毫莫 耳）在甲苯（5毫升）中之溶液内，添加苯甲醛（75毫升，0.74 毫莫耳）。將所形成之混合物加熱至回流，歷經十八小時。 在冷卻至環境溫度後，添加己烷，以產生沉澱作用。過濾 混合物’而得3-(4-嗎福ρ林-4-基苯基）-2-苯基-2,3-二氮ρ奎。坐淋 -4(1Η)-酮（0.16 克，63%)，為灰色固體；1H NMR (300 MHz，CDC13) 7·99 (dd，J = 7.8, 1.2 Hz，1H)，7.51-7.41 (m，1H)，7.34-7.29 (m，2H)， 7.28-7.28 (m，2H)，7.09-7.04 (m，2H)，6·88-6·78 (m，3H)，6.73-6.65 (m， 1H)，6.60 (d，J = 7·8 Hz，1H)，6.03 (s，1H)，3.83 (t，J = 4.5 Hz，4H)，3.10 (t， 128409 -154- 200836743 J = 4·5 Hz，4H). 製備27 2-(4-溴苯基）-3-丁基_2,3-二氳喹唑啉_4(1Η)·酮之合成 Α· Ν-丁基-2-确基苯曱醯胺之合成 將氯化2-硝基-苯甲醯（2.88克，14〇毫莫耳）在二氯甲烷（5 毫升）中之溶液慢慢添加至丁胺（2·77毫升，28 0毫莫耳）、三 乙胺（2.95毫升，21.0毫莫耳）及二氯甲烷（8〇毫升）之冰冷攪 拌混合物中。將混合物於(TC下攪拌一小時，然後倒入水（3〇〇 毫升）中。以二氯曱烷（3x50毫升）萃取所形成之懸浮液。將 合併之有機層以飽和碳酸鈉溶液與水洗滌，以無水硫酸鈉 脫水乾燥，及過濾。在真空中濃縮濾液，獲得怵丁基冬硝 基笨甲醯胺（3.1克’ 100%)，為蠟狀固體：1 η nmR (3〇〇 ΜΗζ， CDC13) δ 8.03 (dd，J = 8.0, 0_9 Ηζ，1Η)，7.64 (td，J = 7.4, 1·2 Ηζ，1Η)， 7.58-7.46 (m，2Η)，5·87-5_74 (s br，1Η)，3.49-3.39 (m，2Η)，1.67-L53 (m， 2H)5 1.48-1.33 (m5 2H)5 0.95 (t9 J = 7.3 Hz5 3H). B· 2-胺基-N-丁基苯曱醯胺之合成 N-丁基-2-硝基苯甲醯胺（3.1克，14·0毫莫耳）在甲醇（1〇〇毫 升）中之懸浮液係經由使氣起泡經過一小時而被脫氣，然後 添加Pd/C (10%，0·74克，1·4毫莫耳）。接著連接氫氣瓶，並 將反應混合物於環境溫度下攪拌十六小時。經過石夕藻土墊 過濾混合物’使濾液在真空中濃縮至乾涸，獲得胺基 丁基苯甲醯胺（2.6 克，100%) : 1H NMR (300 MHz，CDC13) 5 7.28 (dd，J = 7.8，1·9 Hz，1H)，7.23-7.15 (m，1H)，6.74-6.61 (m，2H)，6.11-5.93 (s br，1H)，3.44-3.34 (m，2H)，1.63-1.53 (m，2H)，1.47-1.31 (m，2H)，0.94 (t， 128409 -155- 200836743 J — 7.3 Hz, 3H). C· 2_(4·、/臭本基）-3-丁基-2,3-二氫p奎嗤琳_4(ijj)-酮之合成 於2-胺基-N-丁基苯甲醯胺（〇·2〇克，1〇毫莫耳）在乙醇（18 毫升）中之經攪拌溶液内，添加氫氧化鈉溶液（1〇%，3〇毫 升），接著添加4-溴基苯甲醛。使混合物回流一小時。添加 水（50毫升）。以醋酸乙酯（3 χ 30毫升）萃取混合物。將合併 之有機層以無水硫酸鈉脫水乾燥，及過濾。在真空中濃縮 濾液。使殘留物接受管柱層析（醋酸乙酯/己烷，1/5)，獲得 2-(4_溴苯基)_3·•丁基-2,3-二氫 ρ奎 ϋ坐卩林·4(ιη)_酮（0.22 克，62%): 1 Η NMR (300 MHz，CDC13) 5 7.93 (dd，J = 7.6, 1·5 Ηζ，1Η)，7.48-7.41 (m， 2H)，7·26_7·17 (m，2H)，6.84 (td，J = 8·2, 1·2 Hz，1H)，6.53-6.47 (m，1Η)， 5.86 (s，1H)，4.04-3.91 (m，1H)，2.78-2.65 (m，1H)，1.61-1.47 (m，2H)， 1.37-1.20 (m，2H)，0.87 (t，J = 7.0 Hz, 3H) ; MS (ES+) m/z 359.0 (M + 1)， 357.1 (M-l). 實例1 2-丁基-3-(4-甲氧苯基）峻唆琳-4(3H)-Sli之合成Hz,1H),7.84-7.67 (m,3H), 7.61 (d,J =: 9·0 Hz, 2H), 6.94 (d, J = 9·0 Hz, 2H), 3.76 (t, J = 4.8 Hz, 4H), 3.09 (t, J = 4.8 Hz, 4H); MS (ES+) m/z 328.3 (M + 1). B· 2_Amino·Ν-(4-Fallin-4-yl) Synthesis of Phenyl)benzamine Along with the procedure described in Preparation 21B, and with irrelevant changes, N-(4-morpholin-4-ylphenyl) 2-nitrophenylguanamine was used. Displacement of (3_{[(2_nitrophenyl))]amino}cyclohexyl)carbamic acid tert-butyl ester to give 2-amino-N-(4_wufolin-4-ylphenyl) Benzoic acid amine (59%) as a grey solid: 1 η NMR (300 MHz, CD3OD) (5 9·77 (s, 1 Η), 7.57-7.49 (m, 3 Η), 7.14 (ddd, J = 7.8, 7.8, 1·2 Hz, 1H), 3.88 (d, J = 9.0 Hz, 2H), 6.70 (dd, J = 9.1, 0·9 Hz, 1H), 6.53 (ddd, J = 7.8, 7.8, 1.2 Hz , 1H), 3.70 (t, J = 4·5 Hz, 4H), 3.02 (t, J = 4.5 Hz, 4H); MS (ES+) m/z 320.2 (M + 23). C· 3-(4 Synthesis of 4-amino-indole- 4-(i-hoproline) of phenanthrene _4-ylphenyl)·2_phenyl-2,3-dihydroquinazolidin _4(1H)-one -4-ylphenyl)benzamide ( • 2 g, 0.67 mmol; in toluene (5 ml), benzaldehyde (75 mL, 0.74 mmol) was added. The resulting mixture was heated to reflux for 18 hours. After the ambient temperature, hexane was added to effect precipitation. The mixture was filtered to give 3-(4-fosfosin-4-ylphenyl)-2-phenyl-2,3-diaza ρ. Sodium-4(1Η)-one (0.16 g, 63%) as a gray solid; 1H NMR (300 MHz, CDC13) 7·99 (dd, J = 7.8, 1.2 Hz, 1H), 7.51-7.41 (m ,1H),7.34-7.29 (m,2H), 7.28-7.28 (m,2H),7.09-7.04 (m,2H),6·88-6·78 (m,3H),6.73-6.65 (m, 1H), 6.60 (d, J = 7·8 Hz, 1H), 6.03 (s, 1H), 3.83 (t, J = 4.5 Hz, 4H), 3.10 (t, 128409 -154- 200836743 J = 4·5 Hz,4H). Preparation 27 2-(4-Bromophenyl)-3-butyl-2,3-dioxaquinazoline-4(1Η)·one ketone synthesis Α·Ν-butyl-2- Synthesis of benzoguanamine A solution of 2-nitro-benzamide (2.88 g, 14 mmol) in dichloromethane (5 mL) was slowly added to butylamine (2·77 mL) , 28 0 millimolar), triethylamine 2.95 ml, 21.0 mmol) and dichloromethane (8〇 mL) of ice-cold stirred mixture. The mixture was stirred at (TC) for one hour and then poured into water (3 mL). The resulting suspension was extracted with dichloromethane (3×50 mL). Washed, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo to give succinyl butyl nitro succinamine (3.1 g '100%) as a waxy solid: 1 η nmR (3 〇〇ΜΗζ , CDC13) δ 8.03 (dd, J = 8.0, 0_9 Ηζ, 1Η), 7.64 (td, J = 7.4, 1·2 Ηζ, 1Η), 7.58-7.46 (m, 2Η), 5·87-5_74 (s Br,1Η), 3.49-3.39 (m,2Η),1.67-L53 (m, 2H)5 1.48-1.33 (m5 2H)5 0.95 (t9 J = 7.3 Hz5 3H). B· 2-Amino-N- Synthesis of Butylbenzamine A suspension of N-butyl-2-nitrobenzamide (3.1 g, 14.0 mmol) in methanol (1 mL) was bubbled through air After one hour of degassing, Pd/C (10%, 0. 74 g, 1.4 mmol) was added. The hydrogen cylinder was then connected and the reaction mixture was stirred at ambient temperature for 16 hours.夕藻土垫过滤混合物's the filtrate in a vacuum Reduce to dryness to give aminobutyl benzyl carbamide (2.6 g, 100%): 1H NMR (300 MHz, CDC13) 5 7.28 (dd, J = 7.8,1·9 Hz, 1H), 7.23-7.15 ( m,1H),6.74-6.61 (m,2H),6.11-5.93 (s br,1H),3.44-3.34 (m,2H),1.63-1.53 (m,2H),1.47-1.31 (m,2H) , 0.94 (t, 128409 -155- 200836743 J — 7.3 Hz, 3H). C· 2_(4·,/臭臭基)-3-butyl-2,3-dihydrop-quineline_4(ijj The synthesis of the ketone is carried out in a stirred solution of 2-amino-N-butylbenzamide (〇·2 gram, 1 〇 mmol) in ethanol (18 ml). (1 〇%, 3 〇 ml), followed by the addition of 4-bromobenzaldehyde. The mixture was refluxed for one hour. Water (50 mL) was added. The mixture was extracted with ethyl acetate (3 30 mL). It was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated in vacuo. The residue was applied to column chromatography (ethyl acetate /hexane, 1/5) to give 2-(4-bromophenyl). Butyl-2,3-dihydro-ρ ϋ ϋ · 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 7.6, 1·5 Ηζ,1Η), 7.48-7.41 (m, 2H), 7·26_7·17 (m, 2H), 6.84 (td, J = 8·2, 1·2 Hz, 1H), 6.53 6.47 (m,1Η), 5.86 (s,1H),4.04-3.91 (m,1H),2.78-2.65 (m,1H),1.61-1.47 (m,2H), 1.37-1.20 (m,2H), 0.87 (t, J = 7.0 Hz, 3H); MS (ES+) m/z 359.0 (M + 1), 357.1 (Ml). Example 1 2-butyl-3-(4-methoxyphenyl) Synthesis of Lin-4(3H)-Sli

於2-胺基-N-(4-甲氧苯基）苯甲醯胺（ΐ·〇〇克，4.10毫莫耳）在 N，N-二甲基甲醯胺（35毫升）中之溶液内，在環境溫度下，添 加原戊酸三甲酯（5.7毫升，過量）與醋酸（8.0毫升，過量）。 將反應混合物於85°C下攪拌十六小時，並倒入水（300毫升） 中。以醋酸乙酯（3 χ 70毫升）萃取此懸浮液。將合併之有機 -156- 128409 200836743 層以飽和碳酸鈉溶液與水洗滌，以無水硫酸鈉脫水乾燥， 及過濾。使濾、液在真空中濃縮至乾酒。使殘留物接受管柱 層析（醋酸乙酯/己烷，1/5)，獲得2-丁基-3-(4-甲氧苯基）峻唑 啉-4(3H)-酮（1.11克，88%)，為無色固體：熔點1〇7-1〇9它；1 η NMR (300 MHz，CDC13) 5 8.24 (d5 J = 7·9 Ηζ，1Η)，7.76-7.66 (m，2Η)，7·42 (t， J = 7.4 Ηζ，1Η)，7.17-7.12 (m，2Η)，7.05-7.00 (m，2Η)，3.86 (s，3Η)，2.43 (t， J = 7.6 Hz，2H)，1.69-1.59 (m，2H)，1.30-1.18 (m，2H)，0.80 (t，J = 7.3, 3H) ; 13C NMR (75 MHz，CDC13) 5 162.7, 159.8, 157.6, 147.5, 134.3, 129.8，129.2，127.0，126.9，126.4，120.7，115.0，55.5，35.5，29.2，22.3, 13.6 ； MS (ES+) m/z 309.2 (M + 1). 實例2 3-(3-胺基苯基）-2-丁基p奎吐淋-4(3H)-gig之合成a solution of 2-amino-N-(4-methoxyphenyl)benzamide (ΐ·〇〇克, 4.10 mmol) in N,N-dimethylformamide (35 ml) Within the ambient temperature, trimethyl ortho-valerate (5.7 ml, excess) was added with acetic acid (8.0 mL, excess). The reaction mixture was stirred at 85 ° C for 16 hours and poured into water (300 mL). The suspension was extracted with ethyl acetate (3 χ 70 mL). The combined organic-156-128409 200836743 layers were washed with saturated sodium carbonate solution and water, dried over anhydrous sodium sulfate and filtered. The filtrate and liquid were concentrated in a vacuum to dry wine. The residue was subjected to column chromatography (ethyl acetate / hexanes, 1/5) to give 2-butyl-3-(4-methoxyphenyl) thiazolin-4(3H)-one (1.11 g) , 88%), as colorless solid: melting point 1 〇 7-1 〇 9 it; 1 η NMR (300 MHz, CDC13) 5 8.24 (d5 J = 7·9 Ηζ, 1 Η), 7.76-7.66 (m, 2 Η) ,7·42 (t, J = 7.4 Ηζ, 1Η), 7.17-7.12 (m, 2Η), 7.05-7.00 (m, 2Η), 3.86 (s, 3Η), 2.43 (t, J = 7.6 Hz, 2H ), 1.69-1.59 (m, 2H), 1.30-1.18 (m, 2H), 0.80 (t, J = 7.3, 3H); 13C NMR (75 MHz, CDC13) 5 162.7, 159.8, 157.6, 147.5, 134.3, 129.8, 129.2, 127.0, 126.9, 126.4, 120.7, 115.0, 55.5, 35.5, 29.2, 22.3, 13.6; MS (ES+) m/z 309.2 (M + 1). Example 2 3-(3-Aminophenyl) Synthesis of -2-butyl p-quinone-4(3H)-gig

使 2·丁基-4H-3，1-苯并号 _ _4-g同（0.50 克，2·46 毫莫耳）、1，3-苯二胺（0.28克’ 2.58毫莫耳）在p比咬（5·〇毫升）中之混合物於 ll〇°C下回流六小時。在真空中移除吡啶。使殘留物接受管 柱層析（醋酸乙酯/己烷，1/2)，獲得3-(3-胺基苯基）-2-丁基喳 吐啉·4(3Η)_酮（0.21克，28%)，為無色固體：熔點i5i_i53°C ; lU NMR (300 MHz5 CDC13) 5 8.25 (d? J = 7.9 Hz, 1H)? 7.77-7.64 (m? 2H)，7.42 (td，J = 1.5, 8.2 Hz, 1H)，7.27 (t，J = 7.9 Hz，1H)，6.78-6.72 (m， 1H)，6.61-6.55 (m，1H)，6.53-6.49 (m，1H)，4.05-3.61 (br，2H)，2·47 (t，J = 128409 -157- 200836743 7·6 Hz，2H)，1.74-1.61 (m，2H)，1.33-1 _ 18 (m，2H)，0·81 (t，J = 7.3 Hz， 3H) ; 13C NMR (75 MHz，CDC13) 6 162.8, 157.8, 148.4, 147.9, 138.6, 134.8, 130.9, 127.4, 127.3, 126.8, 121.1，118.2, 116.2, 114.9, 35.6, 29.8, 22.7, 14.1 ; MS (ES+) m/z 294.1 (M + 1)· 實例3 2-丁基-3-(4-羥苯基）喹唑啉-4(3H)-酮之合成2 butyl-4H-3,1-benzox _ _4-g with (0.50 g, 2.46 mmol), 1,3-phenylenediamine (0.28 g ' 2.58 mmol) in p The mixture in the bite (5 ml) was refluxed at ll ° C for six hours. The pyridine was removed in vacuo. The residue was subjected to column chromatography (ethyl acetate / hexane, 1/2) to give 3-(3-aminophenyl)-2-butylpyrazine·4(3Η)-one (0.21 g) , 28%), as colorless solid: melting point i5i_i53°C; lU NMR (300 MHz5 CDC13) 5 8.25 (d? J = 7.9 Hz, 1H)? 7.77-7.64 (m? 2H), 7.42 (td, J = 1.5 , 8.2 Hz, 1H), 7.27 (t, J = 7.9 Hz, 1H), 6.78-6.72 (m, 1H), 6.61-6.55 (m, 1H), 6.53-6.49 (m, 1H), 4.05-3.61 ( Br, 2H), 2·47 (t, J = 128409 -157- 200836743 7·6 Hz, 2H), 1.74-1.61 (m, 2H), 1.33-1 _ 18 (m, 2H), 0·81 ( t, J = 7.3 Hz, 3H) ; 13C NMR (75 MHz, CDC13) 6 162.8, 157.8, 148.4, 147.9, 138.6, 134.8, 130.9, 127.4, 127.3, 126.8, 121.1, 118.2, 116.2, 114.9, 35.6, 29.8 , 22.7, 14.1 ; MS (ES+) m/z 294.1 (M + 1) · Example 3 Synthesis of 2-butyl-3-(4-hydroxyphenyl)quinazoline-4(3H)-one

按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-N-(4-羥基-苯基）-苯甲醯胺置換2-胺基-N-(4-甲氧 基-苯基）-苯甲醯胺，獲得2-丁基-3-(4-羥苯基 &gt;奎唑啉-4(3H)-酮 (79%)，為無色固體：熔點 162_163°C ; iHNMRpOOMHz’CDCU) 5 8·29 (d，J = 7.9 Hz，1H)，7·78 (t，J = 7.0 Hz，1H)，7.72 (s，1H)，7.71-7.69 (m，1H)，7.48 (t，J = 7.9 Hz，1H)，6.99-6.94 (m，2H)，6.77-6.74 (m，2H)， 2.46 (t，J = 7.3 Hz，2H)，1.69-1.59 (m，2H)，1.29細1.17 (m，2H)，0.78 (t，J = 7.3, 3H); 13 C NMR (75 MHz，CDC13) 5 164.1，158.3, 157.7, 148.0, 135.2, 129.2, 128·9, 127.38, 127.35, 127.1，120.7, 117.7, 35.8, 29.7, 22.7, 14.0 ; MS (ES+) m/z 295.1 (M + 1). 實例4 4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯甲醯胺之合成Displacement of 2-amino-N-(4-A with 2-amino-N-(4-hydroxy-phenyl)-benzimidamide according to the procedure as described in Example 1 and with irrelevant changes Oxy-phenyl)-benzamide to give 2-butyl-3-(4-hydroxyphenyl) quinazoline-4(3H)-one (79%) as colorless solid: mp 162. C ; iHNMRpOOMHz 'CDCU) 5 8·29 (d, J = 7.9 Hz, 1H), 7·78 (t, J = 7.0 Hz, 1H), 7.72 (s, 1H), 7.71-7.69 (m, 1H) , 7.48 (t, J = 7.9 Hz, 1H), 6.99-6.94 (m, 2H), 6.77-6.74 (m, 2H), 2.46 (t, J = 7.3 Hz, 2H), 1.69-1.59 (m, 2H) ), 1.29 fine 1.17 (m, 2H), 0.78 (t, J = 7.3, 3H); 13 C NMR (75 MHz, CDC13) 5 164.1, 158.3, 157.7, 148.0, 135.2, 129.2, 128·9, 127.38, 127.35, 127.1, 120.7, 117.7, 35.8, 29.7, 22.7, 14.0; MS (ES+) m/z 295.1 (M + 1). Example 4 4-(2-butyl-4-ketoquinazoline-3 ( Synthesis of 4H)-yl)benzamide

128409 -158- 200836743 按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-N-(4-胺甲醯基苯基）苯甲醯胺置換2-胺基-N-(4-甲 氧基-苯基）-苯甲醯胺，獲得4-(2-丁基-4-酮基喳唑啉-3(4H&gt;基） 苯甲醯胺（53%)，為無色固體：熔點215-217°C ;七NMR (300 MHz，CDC13) 5 8.24 (d，J = 7·9 Hz，1H)，7·98 (d，J = 8·2 Hz，2H)， 7.79-7.69 (m，2H)，7.46 (t，J = 7·9 Hz，1H)，7.34 (d，J = 8.2 Hz，2H)， 6.40-5.50 (br，2H)，2.39 (t，J = 7.6 Hz，2H)，1.69-1.58 (m，2H)，1.29-1.17 (m，2H)，0.79 (t，J = 7.3, 3H) ; 13c NMR (75 MHz，CDC13) (M68.6, 162.8, 156.8, 147.8, 141.0, 135.2, 134.8, 129.4, 129.3, 127.5, 127.3, 127.2, 120.9, 35.9, 29.5, 22·7, 14.1，MS (ES+) m/z 322.1 (M + 1)· 實例5 三氟甲烷磺酸4-(2-丁基-4-酮基喳唑啉)苯酯之合成128409 -158- 200836743 Following the procedure as described in Example 1, and performing an insignificant change, the 2-amino-N-(4-amine-mercaptophenyl)benzamide was used to replace the 2-amino group- N-(4-methoxy-phenyl)-benzamide, 4-(2-butyl-4-ketooxazoline-3(4H&gt;yl)benzamide (53%), Colorless solid: mp 215-217 ° C; NMR (300 MHz, CDC 13) 5 8.24 (d, J = 7·9 Hz, 1H), 7·98 (d, J = 8·2 Hz, 2H), 7.79-7.69 (m, 2H), 7.46 (t, J = 7·9 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 6.40-5.50 (br, 2H), 2.39 (t, J = 7.6 Hz, 2H), 1.69-1.58 (m, 2H), 1.29-1.17 (m, 2H), 0.79 (t, J = 7.3, 3H); 13c NMR (75 MHz, CDC13) (M68.6, 162.8, 156.8, 147.8, 141.0, 135.2, 134.8, 129.4, 129.3, 127.5, 127.3, 127.2, 120.9, 35.9, 29.5, 22·7, 14.1, MS (ES+) m/z 322.1 (M + 1)· Example 5 Trifluoro Synthesis of 4-(2-butyl-4-ketooxazoline) phenyl methanesulfonate

於2-丁基-3_(4-羥苯基 &gt;奎唑啉-4(3H), (〇16克，〇·54毫莫耳）To 2-butyl-3_(4-hydroxyphenyl &gt; quinazoline-4(3H), (〇16 g, 〇·54 mmol)

128409 -159- 200836743 CDC13) 5 8.21 (d，J = 7·9 Ηζ，1Η)，7·79-7·65 (m，2H)，7.49-7.41 (m，3H)， 7.36 (d，J = 9.0 Hz，2H)，2.37 (t，J = 7.9 Hz，2H)，1·69-1·56 (m，2H)， L30-1.17 (m，2H)，0.77 (t，J = 7·3, 3H) ; 13C NMR (75 MHz，CDC13) 5 162.7，156.5，149.9，147.7，137.7，135.2，131.0，127.5，127.3，127.2, 123.2, 120.8, 35.9, 29.4, 22.6, 13.9 ; MS (ES+) m/z 427.0 (M + 1). 實例6 2-丁基-3-{4-[(二苯亞曱基）胺基]苯基}喹唑啉-4(3H)-酮之合成128409 -159- 200836743 CDC13) 5 8.21 (d, J = 7·9 Ηζ, 1Η), 7·79-7·65 (m, 2H), 7.49-7.41 (m, 3H), 7.36 (d, J = 9.0 Hz, 2H), 2.37 (t, J = 7.9 Hz, 2H), 1·69-1·56 (m, 2H), L30-1.17 (m, 2H), 0.77 (t, J = 7.3, 3H) ; 13C NMR (75 MHz, CDC13) 5 162.7, 156.5, 149.9, 147.7, 137.7, 135.2, 131.0, 127.5, 127.3, 127.2, 123.2, 120.8, 35.9, 29.4, 22.6, 13.9; MS (ES+) m/ z 427.0 (M + 1). Example 6 Synthesis of 2-butyl-3-{4-[(diphenylhydrazinyl)amino]phenyl}quinazoline-4(3H)-one

使三氟甲烷磺酸4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯酯（1〇〇 毫克，0.23毫莫耳）、二苯甲酮亞胺（79.6微升，0.46毫莫耳） 在甲苯（10毫升）中之混合物以氮起泡一小時，接著添加醋 酸鈀（5.2毫克，0.023毫莫耳）與碳酸鉋（151毫克，0.46毫莫 耳）。使混合物以氮再起泡二十分鐘，並於ll〇°C下攪拌二 十小時。添加水，以使反應淬滅。以醋酸乙酯（3 X 30毫升） 、 萃取混合物。將合併之有機層以無水硫酸鈉脫水乾燥，及 過濾。在真空中濃縮濾液。使殘留物接受管柱層析（醋酸乙 酯/己烧’ 1八〇) ’獲得2-丁基-3-{4-[(二苯亞甲基）胺基]苯基} 4 唑琳-4(3H)-酮（98 毫克，93%)，為無色固體：1H NMR (300 MHz， CDC13) δ 8.23 (dd5 J = 7.9? 1.2 Hz5 1H)5 7.80-7.63 (m5 4H)? 7.52-7.38 (m? 4H)，7.32-7.25 (m，3H)，7.18-7.11 (m，2H)，7.03_6.97 (m，2H)，6.89-6.82 (m，2H)，2.32 (t，J = 7·9 Hz，2H)，1.69-1.56 (m，2H)，1.30-1.17 (m，2H)， 0.81 (t，J = 7.3 Hz，3H). 128409 -160- 200836743 實例7 3-(4-胺基苯基）_2_丁基喳唑啉-4(3H)•酮之合成4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl trifluoromethanesulfonate (1 mg, 0.23 mmol), benzophenone imine ( 79.6 μl, 0.46 mmol; mixture in toluene (10 mL) was bubbled with nitrogen for one hour, then palladium acetate (5.2 mg, 0.023 mmol) and carbonated (151 mg, 0.46 mmol). . The mixture was again bubbled with nitrogen for twenty minutes and stirred at ll ° C for twenty hours. Water is added to quench the reaction. The mixture was extracted with ethyl acetate (3 X 30 mL). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate / hexane - 1 octa). - Obtained 2-butyl-3-{4-[(diphenylmethylene)amino]phenyl} 4 azole - 4(3H)-one (98 mg, 93%) as colorless solid: 1H NMR (300 MHz, CDC13) δ 8.23 (dd5 J = 7.9? 1.2 Hz5 1H)5 7.80-7.63 (m5 4H)? 7.52-7.38 (m? 4H), 7.32-7.25 (m, 3H), 7.18-7.11 (m, 2H), 7.03_6.97 (m, 2H), 6.89-6.82 (m, 2H), 2.32 (t, J = 7 · 9 Hz, 2H), 1.69-1.56 (m, 2H), 1.30-1.17 (m, 2H), 0.81 (t, J = 7.3 Hz, 3H). 128409 -160- 200836743 Example 7 3-(4-amine Synthesis of phenyl) 2-1-butyloxazoline-4(3H)• ketone

於2-丁基各{4-[(二苯亞甲基）胺基]苯基}喹唑啉-4(3H), (77 毫克，0.17笔莫耳）在四氫呋喃（15毫升）中之經攪拌溶液内， 在環境溫度下慢慢添加鹽酸（2N，5毫升）。將混合物於環境 溫度下授拌兩小時，並倒入鹽酸（1N，60毫升）中。以己院/ 醋酸乙酯之混合溶劑（20/1，20毫升）萃取混合物。分離水層， 且藉由緩慢添加固態碳酸氫鈉中和，直到pH值約7為止。 以醋酸乙酯（3 X 30毫升）萃取混合物。使合併之有機層以無 水硫酸納脫水乾燥，及過濾。在真空中濃縮濾液。使殘留 物接受管柱層析（醋酸乙S旨/己烧，1/1〇)，獲得3-(4-胺基苯 基）-2-丁基π奎吐淋-4(3H)-酮（34毫克，68%)，為無色固體：溶 點 130-132°C ; 1 H NMR (300 MHz，CDC13) 5 8.24 (d，J = 8.2 Hz，1H)， 7.76-7.64 (m，2H)，7.41 (t, J = 8·2 Hz，1H)，6.97 (d，J = 8·2 Hz，2H)，6.76 (d，J = 8·2 Hz，2H)，4.17-3.55 (br，2H)，2.46 (t，J = 7·8 Hz，2H)，1.70-1.57 (m，2H)，1.31-1.16 (m，2H)，0.80 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz， CDC13) 5 163.3，158.5，147.9, 147.5，134.7，129.3，127.9，127.4, 127.2, 126.7, 121.1，116.1，36.0, 29.8, 22.8, 14.1 ; MS (ES+) m/z 294.2 (M + 1). 實例8 5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-2,3-二氫-1H-蜊哚-1-羧酸第 三-丁酯之合成 128409 -161 - 200836743By 2-butyl each {4-[(diphenylmethylene)amino]phenyl}quinazoline-4(3H), (77 mg, 0.17 mol) in tetrahydrofuran (15 mL) Hydrochloric acid (2N, 5 ml) was slowly added to the solution at ambient temperature. The mixture was stirred at ambient temperature for two hours and poured into hydrochloric acid (1N, 60 mL). The mixture was extracted with a mixture of hexanes / ethyl acetate (20/1, 20 ml). The aqueous layer was separated and neutralized by slowly adding solid sodium bicarbonate until the pH was about 7. The mixture was extracted with ethyl acetate (3 X 30 mL). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (acetic acid ethyl acetate / hexane, 1/1 〇) to give 3-(4-aminophenyl)-2-butyl π ketoxi-4(3H)-one. (34 mg, 68%) as colorless solid: melting point 130-132 ° C; 1 H NMR (300 MHz, CDC13) 5 8.24 (d, J = 8.2 Hz, 1H), 7.76-7.64 (m, 2H) , 7.41 (t, J = 8·2 Hz, 1H), 6.97 (d, J = 8·2 Hz, 2H), 6.76 (d, J = 8·2 Hz, 2H), 4.17-3.55 (br, 2H) ), 2.46 (t, J = 7·8 Hz, 2H), 1.70-1.57 (m, 2H), 1.31-1.16 (m, 2H), 0.80 (t, J = 7·3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 163.3, 158.5, 147.9, 147.5, 134.7, 129.3, 127.9, 127.4, 127.2, 126.7, 121.1, 116.1, 36.0, 29.8, 22.8, 14.1; MS (ES+) m/z 294.2 (M + 1). Example 8 5-(2-butyl-4-ketoquinazolin-3(4H)-yl)-2,3-dihydro-1H-indole-1-carboxylic acid tert-butyl Synthesis of esters 128409 -161 - 200836743

按照如實例1中所述之程序，且施行無關緊要之改變， 使用5-{[(2-胺基苯基）羰基]胺基}-2,3-二氫-1H-啕哚-1-羧酸第 三-丁酯置換2-胺基-N-(4-甲氧基-苯基）-苯甲醯胺，獲得5-(2-丁基-4-酮基喳唑琳-3(4H)-基）-2,3-二氫-1H-吲哚-1-羧酸第三-丁 酯（82%)，為無色固體：1H NMR (300 MHz，CDC13) (5 8.21 (dd，J = 1.2, 8·2 Hz，1H)，8.06-7.83 (br，1Η)，7.73-7.63 (m，2H)，7.39 (ddd，J = 1·5, 8.2, 8.2 Hz，1H)，7·01-6·95 (m，2H)，4.02 (t，J = 8.8 Hz，2H)，3·12 (t，J = 8.8 Hz，2H)，2.43 (t，J = 7·6 Hz，2H)，1.71-1.50 (m，11H)，1.30-U7 (m， 2H)，0.80 (t，J = 7.3, 3H) ; 13C NMR (75 MHz，CDC13) (M63.1，157.9, 152.7, 147.8, 134.7, 131.4, 127.6, 127.3, 127.2, 126.7, 120.9, 115.6, 48.2, 35.8, 29.6, 28.7, 22.6, 14.1 ; MS (ES+) m/z 420.1 (M + 1). 實例9 2叮基各(2,3_二氫-1H-吲哚-5_基）喳唑啉-4(3H)_顯I之合成5-{[(2-Aminophenyl)carbonyl]amino}-2,3-dihydro-1H-indole-1- was used according to the procedure as described in Example 1 and insignificantly changed. Displacement of 2-amino-N-(4-methoxy-phenyl)-benzamide with a carboxylic acid tert-butyl ester to give 5-(2-butyl-4-ketoindole-3) 4H)-yl)-2,3-dihydro-1H-indole-1-carboxylic acid tert-butyl ester (82%) as colorless solid: 1H NMR (300 MHz, CDC13) (5 8.21 (dd, J = 1.2, 8·2 Hz, 1H), 8.06-7.83 (br, 1Η), 7.73-7.63 (m, 2H), 7.39 (ddd, J = 1. 5, 8.2, 8.2 Hz, 1H), 7· 01-6·95 (m, 2H), 4.02 (t, J = 8.8 Hz, 2H), 3·12 (t, J = 8.8 Hz, 2H), 2.43 (t, J = 7·6 Hz, 2H) , 1.71-1.50 (m, 11H), 1.30-U7 (m, 2H), 0.80 (t, J = 7.3, 3H); 13C NMR (75 MHz, CDC13) (M63.1, 157.9, 152.7, 147.8, 134.7 , 131.4, 127.6, 127.3, 127.2, 126.7, 120.9, 115.6, 48.2, 35.8, 29.6, 28.7, 22.6, 14.1; MS (ES+) m/z 420.1 (M + 1). Example 9 2 thiol (2, Synthesis of 3_dihydro-1H-indol-5-yl)oxazoline-4(3H)_display I

於5-(2-丁基冰_基喳唑啉_3(4H)•基）_2,3·二氫]沁吲哚+羧 酸第三-丁酯（80毫克，〇19毫莫耳）在二氣甲烷（7 〇毫升）中之 經攪拌溶液内，在環境溫度下添加三氟醋酸（L5毫升，過 量）。將混合物於環境溫度下授拌十六小時。使混合物在真 工中》辰細至乾涸，使殘留物溶於醋酸乙酯（50毫升）中。將 128409 -162- 200836743 混合物以飽和碳酸鈉溶液與水洗滌，以無水硫酸鈉脫水乾 燥，及過濾。在真空中濃縮濾液。使殘留物接受管柱層析（醋 酸乙酯/己烷，1/2)，獲得2-丁基-3-(2,3-二氫-1H-啕哚-5-基）喳 唑琳-4(3H)·酮（45毫克，74%)，為無色固體：熔點i69-170°C ; 4 NMR (300 MHz，CDC13) δ 8.23 (dd，J = 1.2, 8·2 Hz，1H)，7.75-7.63 (m，2H)，7·40 (ddd，J = 1·5, 8.2, 8·2 Hz，1H)，6.89 (s，1H)，6·80 (dd，J = 2.0, 7.9 Hz, 1H)，6.66 (d，J = 8·2 Hz，1H)，4.38-3.24 (br，1H)，3·61 (t，J = 8.2 Hz，2H)，3.31 (t，J = 8·5 Hz，2H)，2.46 (t，J = 7.6 Hz，2H)，1.71-1.59 (m, 2H)，1.31-1.18 (m，2H)，0.80 (t，J = 7.3, 3H); 13 C NMR (75 MHz, CDC13) ά 163.4, 158.7，152.6，147.9, 134.6, 131.1，127.9, 127.4, 127.2, 126.6, 124.6, 121.1，109.71，109.70, 47.9, 35.9, 29.9, 29.7, 22.7, 14.1 ; MS (ES+) m/z 320.2 (M + 1). 實例10 4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯磺醯胺之合成5-(2-butyl ice-yloxazoline_3(4H)•yl)_2,3·dihydro]indole+carboxylic acid tert-butyl ester (80 mg, 〇19 mmol) Trifluoroacetic acid (L5 mL, excess) was added to the stirred solution in di-methane (7 mL) at ambient temperature. The mixture was stirred at ambient temperature for sixteen hours. The mixture was allowed to dry to dryness and the residue was dissolved in ethyl acetate (50 ml). The mixture of 128409 - 162 - 200836743 was washed with saturated sodium carbonate solution and water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/2) to give 2-butyl-3-(2,3-dihydro-1H-indol-5-yl)indazole- 4(3H)·one (45 mg, 74%) as a colorless solid: m.p., m.sup.ssssssssssssssssssssssssssssssssssssssssssssss 7.75-7.63 (m, 2H), 7·40 (ddd, J = 1·5, 8.2, 8·2 Hz, 1H), 6.89 (s, 1H), 6·80 (dd, J = 2.0, 7.9 Hz , 1H), 6.66 (d, J = 8·2 Hz, 1H), 4.38-3.24 (br, 1H), 3·61 (t, J = 8.2 Hz, 2H), 3.31 (t, J = 8·5 Hz, 2H), 2.46 (t, J = 7.6 Hz, 2H), 1.71-1.59 (m, 2H), 1.31-1.18 (m, 2H), 0.80 (t, J = 7.3, 3H); 13 C NMR ( 75 MHz, CDC13) ά 163.4, 158.7, 152.6, 147.9, 134.6, 131.1, 127.9, 127.4, 127.2, 126.6, 124.6, 121.1, 109.71, 109.70, 47.9, 35.9, 29.9, 29.7, 22.7, 14.1 ; MS (ES+) m/z 320.2 (M + 1). Example 10 Synthesis of 4-(2-butyl-4-ketooxazoline-3(4H)-yl)benzenesulfonamide

按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-N-(4-胺磺醯基苯基）苯甲醯胺置換2-胺基-N-(4-甲 氧基-苯基）-苯甲醯胺，獲得4-(2-丁基基峻嗤琳-3(4H)-基） 苯磺醯胺（72%)，為無色固體：熔點211-213°C ; 1H NMR (300 MHz，CDC13) 5 8.14 (d5 J = 7·9 Ηζ，1Η)，8·03 (d，J = 8·5 Ηζ，2Η)，7.90 (t， J = 7.9 Hz，1H)，7.76-7.70 (m，3H)，7.63-7.53 (m，3H)，2.36 (t，J = 7.6 Hz， 2H)，1.72-1.60 (m，2H)，1.32-1.18 (m，2H)，0.81 (t，J = 7.3, 3H); 13 C NMR 128409 -163 - 200836743 (75 MHz, CDC13) 5 162.4, 157.1，148.1，145.5, 141.2, 135.7, 130.6, 127.9, 127.87, 127.6, 127.2, 121.3, 35.7, 28.9, 22.5, 14.6; MS (ES+) m/z 358.1 (M + !)· 實例11 4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯甲酸甲酯之合成Displacement of 2-amino-N-(4-) with 2-amino-N-(4-amine sulfonylphenyl)benzamide according to the procedure as described in Example 1 and subject to insignificant changes Methoxy-phenyl)-benzamide, 4-(2-butyl quinone-3(4H)-yl) benzenesulfonamide (72%) as colorless solid: m.p. °C ; 1H NMR (300 MHz, CDC13) 5 8.14 (d5 J = 7·9 Ηζ, 1Η), 8·03 (d, J = 8·5 Ηζ, 2Η), 7.90 (t, J = 7.9 Hz, 1H), 7.76-7.70 (m, 3H), 7.63-7.53 (m, 3H), 2.36 (t, J = 7.6 Hz, 2H), 1.72-1.60 (m, 2H), 1.32-1.18 (m, 2H) , 0.81 (t, J = 7.3, 3H); 13 C NMR 128409 -163 - 200836743 (75 MHz, CDC13) 5 162.4, 157.1, 148.1, 145.5, 141.2, 135.7, 130.6, 127.9, 127.87, 127.6, 127.2, 121.3 , 35.7, 28.9, 22.5, 14.6; MS (ES+) m/z 358.1 (M + !) · Example 11 4-(2-butyl-4-ketoquinazolin-3(4H)-yl)benzoic acid Synthesis of methyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用4-{[(2-胺基苯基）幾基]胺基}苯甲酸甲酯置換2-胺基-N-(4-甲氧基-苯基）-苯甲醯胺，獲得4-(2•丁基-4-酮基喹唑啉-3(4H)-基）苯甲酸甲酯（68%)，為無色固體：熔點200-20 Γ(： ; 1H NMR (300 MHz，CDC13) 5 8.20-8.13 (m，3Η)，7.73-7.60 (m，2Η)，7.42-7.28 (m， 3H)，3·89 (s，3H)，2.33 (t，J = 7·8 Hz，2H)，1.66-1.54 (m，2H)，1.25-1.11 (m， 2H)，0.74 (t，J = 7.3 Hz，3H); 13 C NMR (75 MHz, CDC13) (5 166.2, 162.4, 156.4, 147.6, 141.7, 134.8, 131.3, 131·2, 128.9, 127.3, 127.1，126.9, 120.7, 52.6, 35.7, 29.3, 22.4, 13.9 » MS (ES+) m/z 337.0 (M + 1). 實例12 5-(2丁基-4-酮基p奎唾琳_3(4H)_基卜朵小羧酸第三-丁醋之 合成Displacement of 2-amino-N-(4) with methyl 4-{[(2-aminophenyl)alkyl]amino}benzoate according to the procedure as described in Example 1 and subject to insignificant changes -Methoxy-phenyl)-benzamide to give methyl 4-(2 -butyl-4-ketoquinazolin-3(4H)-yl)benzoate (68%) as a colourless solid : melting point 200-20 Γ (: ; 1H NMR (300 MHz, CDC13) 5 8.20-8.13 (m, 3 Η), 7.73-7.60 (m, 2 Η), 7.42-7.28 (m, 3H), 3·89 (s , 3H), 2.33 (t, J = 7·8 Hz, 2H), 1.66-1.54 (m, 2H), 1.25-1.11 (m, 2H), 0.74 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) (5 166.2, 162.4, 156.4, 147.6, 141.7, 134.8, 131.3, 131·2, 128.9, 127.3, 127.1, 126.9, 120.7, 52.6, 35.7, 29.3, 22.4, 13.9 » MS (ES+ m/z 337.0 (M + 1). Example 12 Synthesis of 5-(2-butyl-4-keto-p-quineline_3(4H)_kibdoricarboxylic acid third-butyl vinegar

按照如實例1中所述之程序，且施行無關緊要之改變 128409 -164- 200836743 使用5-{[(2-胺基苯基）幾基]胺基}_1H-吲哚-i_羧酸第三_丁酯置 換2_胺基-N-(4-甲氧基-苯基）-苯甲醯胺，獲得5-(2-丁基-4-酮基 喹唑啉-3(4H)-基）-1Η-啕哚小羧酸第三-丁酯（85%)，為無色固 體：4 NMR (300 MHz，CDC13) 5 8.27 (dd，J = 8.2, 8·2 Hz，2H)， 7.78-7.64 (m，3H)，7,47-7.39 (m，2H)，7.14 (dd，J = 8.8, 2·0 Hz，1H)，6·60 (d，J = 3.8 Hz，1H)，2.43 (t，J = 7.6 Hz，2H)，1·71-1·50 (m，11H)，1.30-U7 (m，2H)，0·77 (t，J = 7.3, 3H). 實例13 丁基丨嗓_5·基）峻。坐琳-4(3H)-S同之合成Following the procedure as described in Example 1, and performing an insignificant change 128409-164-200836743 using 5-{[(2-aminophenyl)alkyl]amine}_1H-吲哚-i-carboxylic acid Tri-butyl ester replaces 2-amino-N-(4-methoxy-phenyl)-benzamide to give 5-(2-butyl-4-ketoquinazolin-3(4H)- Base)-1Η-啕哚 small carboxylic acid tert-butyl ester (85%) as colorless solid: 4 NMR (300 MHz, CDC13) 5 8.27 (dd, J = 8.2, 8·2 Hz, 2H), 7.78 -7.64 (m,3H),7,47-7.39 (m,2H),7.14 (dd,J = 8.8, 2·0 Hz,1H),6·60 (d,J = 3.8 Hz,1H),2.43 (t, J = 7.6 Hz, 2H), 1·71-1·50 (m, 11H), 1.30-U7 (m, 2H), 0·77 (t, J = 7.3, 3H). Example 13 Butyl丨嗓_5·基) Jun. Sitting Lin-4(3H)-S with the synthesis

按照如實例9中所述之程序，且施行無關緊要之改變， 使用5-(2-丁基-4-酮基喳唑啉·3(4Η)_基哚-1-羧酸第三-丁 酯置換5-(2-丁基冰酮基喳唑啉-3(4H)-基）-2,3-二氫-1H-W哚小 羧酸第三-丁酯，獲得2-丁基-3-(1Η-吲哚-5-基 &gt;奎唑啉·4(3Η)_酮 (88%)，為無色固體：熔點 205-207°C ; 1H NMR (300 MHz，CDC13) 5 8.63 (s，1H)，8.29 (d，J = 7.3 Hz，1H)，7.78-7.68 (m，2H)，7.48-7.41 (m， 2H)，7.35 (d，J = 7·9 Hz，1H)，7.21 (d，J = 3.0 Hz，1H)，6.93 (dd，J = 2.0, 8·4 Hz，1H)，6.56-6.52 (m，1H)，2.45 (t，J = 7·8 Hz，2H)，1.72-1.58 (m，2H)， 1.25-1.12 (m，2H)，0.75 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) δ 163.3，158.4，147.7，135.7，134.4，129.3，128.5，127.1，126.9，126.4, 125.9, 121.4, 120.9, 120.1，112.3, 103·1，35.6, 29.4, 22.3, 13.7 ; MS (ES+) m/z 318.1 (M + 1). 128409 -165- 200836743 實例14 [4-(2-丁基-4-酮基喹唑啉·3(4Η)_基）苯基]胺基甲酸第三_丁酯之 合成5-(2-butyl-4-ketooxazoline·3(4Η)_ylindole-1-carboxylic acid third-butyl was used according to the procedure as described in Example 9, and the insignificant change was carried out. Ester replacement of 5-(2-butylrhosyloxazoline-3(4H)-yl)-2,3-dihydro-1H-W-indole carboxylic acid tert-butyl ester to give 2-butyl- 3-(1Η-吲哚-5-yl)&gt; quinazoline·4(3Η)-one (88%) as colorless solid: mp 205-207°C; 1H NMR (300 MHz, CDC13) 5 8.63 ( s,1H), 8.29 (d, J = 7.3 Hz, 1H), 7.78-7.68 (m, 2H), 7.48-7.41 (m, 2H), 7.35 (d, J = 7·9 Hz, 1H), 7.21. (d, J = 3.0 Hz, 1H), 6.93 (dd, J = 2.0, 8·4 Hz, 1H), 6.56-6.52 (m, 1H), 2.45 (t, J = 7·8 Hz, 2H), 1.72-1.58 (m, 2H), 1.25-1.12 (m, 2H), 0.75 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) δ 163.3, 158.4, 147.7, 135.7, 134.4, 129.3, 128.5, 127.1, 126.9, 126.4, 125.9, 121.4, 120.9, 120.1, 112.3, 103·1, 35.6, 29.4, 22.3, 13.7; MS (ES+) m/z 318.1 (M + 1). 128409 -165- 200836743 Example 14 [4-(2-Butyl-4-ketoquinazoline·3(4Η)-yl)phenyl]carbamic acid tert-butyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用（4-{[(2-胺基苯基）幾基]胺基}苯基）胺基甲酸第三·丁酯置 換2-胺基-Ν-(4-甲氧基-苯基苯甲醯胺，獲得[4_(2_丁基冬酮基 喹唾啉_3(4Η)-基）苯基]胺基曱酸第三-丁酯（77〇/〇)，為無色固 體：1H NMR (300 MHz，CDC13) 5 8.28-8.22 (m，1Η)，7.78-7.65 (m，2Η)， 7·52 (d，J = 8·5 Hz，1H)，7.47-7.39 (m，1H)，7.18-7_10 (m，2H)，6.84-6.72 (m，1H)，7.78-7.68 (m，2H)，2.42 (t，J = 7·8 Hz，2H)，1.73-1.55 (m，2H)， 1·50 (s，9H)，1.31-1.16 (m，2H)，0.80 (t，J = 7.3 Hz，3H). 實例15 [4-(4-i同基-2-丙基喹唑啉-3(4H)_基）苯基]胺基甲酸第三·丁酯之 合成Following the procedure as described in Example 1, and performing an insignificant change, using (4-{[(2-aminophenyl))amino}phenyl}amino) carboxylic acid tert-butyl ester 2 -Amino-indole-(4-methoxy-phenylbenzamide), obtaining [4_(2-butylbutanylquinoxalin-3(4Η)-yl)phenyl]amino decanoic acid Tri-butyl ester (77 〇 / 〇), a colorless solid: 1H NMR (300 MHz, CDC13) 5 8.28-8.22 (m, 1 Η), 7.78-7.65 (m, 2 Η), 7·52 (d, J = 8·5 Hz, 1H), 7.47-7.39 (m, 1H), 7.18-7_10 (m, 2H), 6.84-6.72 (m, 1H), 7.78-7.68 (m, 2H), 2.42 (t, J = 7·8 Hz, 2H), 1.73-1.55 (m, 2H), 1·50 (s, 9H), 1.31-1.16 (m, 2H), 0.80 (t, J = 7.3 Hz, 3H). Example 15 [ Synthesis of 4-(4-i-yl-2-ylquinazolin-3(4H)-yl)phenyl]aminocarboxylic acid tert-butyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用（4·{[(2-胺基苯基）羰基]胺基}苯基）胺基甲酸第三_丁酯置 換2-胺基-Ν-(4-甲氧基-苯基）-苯甲醯胺，及原丁酸三甲酯置換 原戊酸三曱酯，獲得[4-(4-酮基_2_丙基喹唑啉-3(4Η)-基）苯基] 128409 -166- 200836743 胺基甲酸第三-丁酯（94%)，為無色固體：1 η NMR (300 MHz， CDC13) 5 8.28-8.22 (m，1H)，7.78-7.65 (m，2H)，7.54-7.47 (m，2H)， 7-36-7.29 (m，1H)，7.15-7.07 (m，2H)，6.95 (s，1H)，2.39 (t，J = 7.8 Hz，2H)， 1·77-1·61 (m，2H)，1.48 (s，9H)，0.85 (t，J = 7·3 Hz，3H). 實例16 3-(4-胺基苯基）-2-丙基p奎ϋ坐淋_4(3H)-g同之合成Displacement of (4·{[(2-aminophenyl)carbonyl]amino}phenyl)aminocarbamic acid tert-butyl ester according to the procedure as described in Example 1 and subject to irrelevant changes Amino-indole-(4-methoxy-phenyl)-benzamide, and trimethyl orthobutyrate to replace tridecyl ortho-valerate to obtain [4-(4-keto-2-propyl) Quinazoline-3(4Η)-yl)phenyl] 128409-166- 200836743 Tert-butyl carbamic acid ester (94%) as colorless solid: 1 η NMR (300 MHz, CDC13) 5 8.28-8.22 ( m,1H), 7.78-7.65 (m,2H),7.54-7.47 (m,2H), 7-36-7.29 (m,1H),7.15-7.07 (m,2H),6.95 (s,1H), 2.39 (t, J = 7.8 Hz, 2H), 1·77-1·61 (m, 2H), 1.48 (s, 9H), 0.85 (t, J = 7·3 Hz, 3H). Example 16 3- (4-Aminophenyl)-2-propyl p-quinone sitting _4(3H)-g

按照如實例9中所述之程序，且施行無關緊要之改變， 使用[4-(4-酮基-2-丙基峻唑淋-3(4H)-基）苯基]胺基甲酸第三-丁 酉旨置換5-(2-丁基-4-酮基峻。坐琳_3(4H)-基）-2,3-二氫-1H-4卜朵-1· 竣酸弟二-丁酷’獲得3-(4-胺基苯基）-2-丙基峻σ坐琳-4(3H)-嗣 (68%)，為無色固體·· 1 H NMR (300 MHz，CDC13) 5 8.24 (dd，J = 1.2, 8·2 Hz，1H)，7.76-7.65 (m，2H)，7.42 (dt，J = 1.2, 8·2 Hz，1H)，7.00-6.94 (m，2H)，6.80-6.73 (m，2H)，4.39-3.21 (br，2H)，2.43 (t，J = 7·6 Hz，2H)， 1.76-1.62 (m，2H)，0.86 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) δ 163.2，158.3，147.8，147.5，134.7，129.3，127.9，127.4，127.2，126.7, 121.1，116·1，38.0, 21.0, 14·2 ; MS (ES+) m/z 280·1 (M + 1)· 實例17 [4-(2-乙基-4-酮基喳唑啉-3(4H)-基）苯基]胺基甲酸第三-丁酯之 合成Following the procedure as described in Example 9, and applying an insignificant change, [4-(4-keto-2-propylrimazole--3(4H)-yl)phenyl]carbamic acid was used as the third - Dingzhi is intended to replace 5-(2-butyl-4-keto-Jun. Selin _3(4H)-yl)-2,3-dihydro-1H-4bido-1· citrate di-butyl Cool's 3-(4-Aminophenyl)-2-propyl sulphate-4(3H)-indole (68%) as a colorless solid.··············· (dd, J = 1.2, 8·2 Hz, 1H), 7.76-7.65 (m, 2H), 7.42 (dt, J = 1.2, 8·2 Hz, 1H), 7.00-6.94 (m, 2H), 6.80 -6.73 (m, 2H), 4.39-3.21 (br, 2H), 2.43 (t, J = 7·6 Hz, 2H), 1.76-1.62 (m, 2H), 0.86 (t, J = 7.3 Hz) , 3H); 13 C NMR (75 MHz, CDC13) δ 163.2, 158.3, 147.8, 147.5, 134.7, 129.3, 127.9, 127.4, 127.2, 126.7, 121.1, 116·1, 38.0, 21.0, 14·2; MS ( ES+) m/z 280·1 (M + 1)· Example 17 [4-(2-ethyl-4-ketooxazoline-3(4H)-yl)phenyl]carbamic acid tert-butyl Ester synthesis

128409 -167- 200836743 按照如實例1中所述之程序，且施行無關緊要之改變， 使用（4-{[(2-胺基苯基）羰基]胺基}苯基）胺基甲酸第三_丁酯置 換2-胺基-N-(4-甲氧基-苯基）-苯甲醯胺，及原丙酸三乙酯置換 原戊酸三甲酯，獲得[4-(2-乙基-4-酮基喹唑啉-3(4H&gt;基）苯基] 胺基甲酸第三-丁酯（94%)，為無色固體：1H NMR (300 MHz， CDC13) 5 8.28-8.22 (m，1H)，7.78-7.65 (m，2H)，7·52-7.39 (m，3H)，7·16 (s，1H)，7.13-7.06 (m，2H)，2.44 (q，J = 7.8 Hz，2H)，1.46 (s，9H)，1·18 (t，J =7.3 Hz，3H). 實例18 3-(4-胺基苯基）-2-乙基喹唑啉-4(3H)-酮之合成128409-167-200836743 According to the procedure as described in Example 1, and irrelevant changes were made, using (4-{[(2-aminophenyl)carbonyl]amino}phenyl)aminocarboxylic acid third_ Butyl ester replaces 2-amino-N-(4-methoxy-phenyl)-benzamide, and triethyl orthopropionate replaces trimethyl ortho-valerate to obtain [4-(2-ethyl) 4-ketoquinazoline-3(4H&gt;yl)phenyl] carbamic acid tert-butyl ester (94%) as colorless solid: 1H NMR (300 MHz, CDC13) 5 8.28-8.22 (m, 1H), 7.78-7.65 (m, 2H), 7·52-7.39 (m, 3H), 7·16 (s, 1H), 7.13-7.06 (m, 2H), 2.44 (q, J = 7.8 Hz, 2H), 1.46 (s, 9H), 1·18 (t, J = 7.3 Hz, 3H). Example 18 3-(4-Aminophenyl)-2-ethylquinazoline-4(3H)- Ketone synthesis

使用[4-(2-乙基-4-酮基喹唑啉-3(4H)-基）苯基]胺基甲酸第三-丁 酯置換5-(2-丁基-4-酮基喳唑啉-3(4H)-基）-2,3-二氫-1H-蜊哚小 羧酸第三-丁酯，獲得3-(4-胺基苯基）-2_乙基喳唑啉-4(3H)-酮 (79%)，為無色固體：旧 NMR (300 MHz，CD3OD) 5 8.17 (dd，J = 1.2, 8·2 Hz，1H)，7.82 (dt，J = 1.2, 8.2 Hz，1H)，7.73-7.68 (m，1H)，7.50 (dt， J = 1.2, 8·2 Hz，1H)，7.04-6.98 (m，2H)，6.87-6.81 (m，2H)，2.52 (q，J = 7·3 Hz，2H)，1.19 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz，CD3 OD) (5 165.4, 162.0, 151.1，149·6, 136.6, 130.7, 128.5, 128.4, 128.4, 128.3, 122.4, 117.3, 30.95 1 2.6 ； MS (ES+) m/z 266.2 (M + 1). 128409 -168- 200836743 實例19 3-(4-溴苯基）-2-丁基喹唑啉-4(3H)-酮之合成Displacement of 5-(2-butyl-4-ketoindole) with [4-(2-ethyl-4-ketoquinazolin-3(4H)-yl)phenyl]carbamic acid tert-butyl ester 3-(butyl)-(4H)-yl)-2,3-dihydro-1H-indole small carboxylic acid to give 3-(4-aminophenyl)-2-ethyloxazoline -4(3H)-one (79%) as colorless solid: old NMR (300 MHz, CD3OD) 5 8.17 (dd, J = 1.2, 8·2 Hz, 1H), 7.82 (dt, J = 1.2, 8.2 Hz,1H), 7.73-7.68 (m,1H), 7.50 (dt, J = 1.2, 8·2 Hz, 1H), 7.04-6.98 (m, 2H), 6.87-6.81 (m, 2H), 2.52 ( q, J = 7·3 Hz, 2H), 1.19 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CD3 OD) (5 165.4, 162.0, 151.1, 149·6, 136.6, 130.7, 128.5, 128.4, 128.4, 128.3, 122.4, 117.3, 30.95 1 2.6 ; MS (ES+) m/z 266.2 (M + 1). 128409 -168- 200836743 Example 19 3-(4-bromophenyl)-2-butene Synthesis of quinazolin-4(3H)-one

按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-N-(4-溴苯基）苯甲醯胺置換2-胺基-N-(4-甲氧基-苯 基）-苯甲醯胺，獲得3-(4-溴苯基）-2-丁基喳唑啉-4(3H)-酮（79%)， 為無色固體：熔點110-111°(：;111&gt;^11(300]\«^，€〇(：13)(58.23- 8.18 (m，1H)，7.76-7.63 (m，4H)，7.46-7.39 (m，1H)，7.15-7.09 (m，2H)， 2.39 (t，J = 7.8 Hz，2H)，1.70-1.59 (m，2H)，1.32-1.18 (m，2H)，0·80 (t，J = 7.3 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.1，156.3, 147.3, 136.2, 134.4, 132.9, 130.0, 126.9, 126.8, 126.5, 123.2, 120.4, 35.4, 28.9, 22·1， 13.6 ； MS (ES+) m/z 357.1 (M + 1). 實例20 2-丁基-3-(2-硫基-1H-苯并味峻-5-基）p奎嗤琳-4(3H)-_之合成The 2-amino-N-(4-methoxyl group was replaced with 2-amino-N-(4-bromophenyl)benzamide using the procedures described in Example 1 and with irrelevant changes. -Phenyl)-benzamide to give 3-(4-bromophenyl)-2-butyloxazolyl-4(3H)-one (79%) as a colourless solid: mp. :;111&gt;^11(300]\«^,€〇(:13)(58.23- 8.18 (m,1H),7.76-7.63 (m,4H),7.46-7.39 (m,1H),7.15-7.09 (m, 2H), 2.39 (t, J = 7.8 Hz, 2H), 1.70-1.59 (m, 2H), 1.32-1.18 (m, 2H), 0·80 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.1, 156.3, 147.3, 136.2, 134.4, 132.9, 130.0, 126.9, 126.8, 126.5, 123.2, 120.4, 35.4, 28.9, 22·1, 13.6 ; MS (ES+) m/z 357.1 (M + 1). Example 20 Synthesis of 2-butyl-3-(2-thio-1H-benzoxanth-5-yl)p-quineline-4(3H)-_

Η 按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-Ν-(2-硫基-1Η-苯并味吐-5_基）苯甲驢胺置換2—胺基 -Ν-(4-甲氧基-苯基）-苯甲醯胺，獲得2-丁基-3-(2-硫基_1Η_苯并 味π坐-5-基）峻σ坐淋-4(3Η)-晒（26%) ’為無色固體：溶點&gt;23〇。〇; 1H NMR (300 MHz，DMSO-d6) 5 12.76 (s，2Η)，8.13 (dd，J = 1.2, 7·9 Ηζ， 128409 -169- 200836743 1Η)，7·87 (dt，J = 1.4, 8·0 Ηζ，1Η)，7.71 (d，J = 7.6 Hz，1H)，7.55 (dt，J = 1.1，8.0 Hz，1H)，7.33導7.28 (m，2H)，7.23-7.16 (m，1H)，2.37 (t，J = 7.8 Hz， 2H)，1.71-1.59 (m，2H)，1.30-1.16 (m，2H)，0.78 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz，DMSO-d6) 5 170.4，162.7，158.3，148.1，135.4，133.7, 133.3, 132.8, 127.7, 127.3, 127.2, 123.8, 121.5, 111.0, 110.7, 35.6, 29·2, 22.5，14·6 ; MS (ES+) m/z 351.1 (M + 1). 實例21 2-丁基-3-(2-酮基-2,3-二氫-1，3-苯并p号。坐-6-基 &gt;奎唾琳-4(3H)-酮 之合成Η In accordance with the procedure as described in Example 1, and performing an insignificant change, 2-amino-indole-(2-thiol-indole-benzopyrene-5-yl)benzamide was used to replace 2- Amino-indole-(4-methoxy-phenyl)-benzamide, obtaining 2-butyl-3-(2-thiol-indene-benzoic π-spin-5-yl)淋-4(3Η)-Sun (26%) 'is a colorless solid: melting point> 23〇. 〇; 1H NMR (300 MHz, DMSO-d6) 5 12.76 (s, 2 Η), 8.13 (dd, J = 1.2, 7·9 Ηζ, 128409 -169- 200836743 1Η), 7·87 (dt, J = 1.4 , 8·0 Ηζ,1Η), 7.71 (d, J = 7.6 Hz, 1H), 7.55 (dt, J = 1.1, 8.0 Hz, 1H), 7.33, 7.28 (m, 2H), 7.23-7.16 (m, 1H), 2.37 (t, J = 7.8 Hz, 2H), 1.71-1.59 (m, 2H), 1.30-1.16 (m, 2H), 0.78 (t, J = 7·3 Hz, 3H); 13C NMR ( 75 MHz, DMSO-d6) 5 170.4, 162.7, 158.3, 148.1, 135.4, 133.7, 133.3, 132.8, 127.7, 127.3, 127.2, 123.8, 121.5, 111.0, 110.7, 35.6, 29·2, 22.5, 14·6; MS (ES+) m/z 351.1 (M + 1). Example 21 2-butyl-3-(2-keto-2,3-dihydro-1,3-benzop. &gt;Synthesis of quetia-4 (3H)-ketone

按照如實例1中所述之程序，且施行無關緊要之改變， 使用2-胺基-N-(2-酮基-2,3-二氫-1,3-苯并p号唾-6-基）苯甲醯胺置 換2-胺基_N-(4-甲氧基-苯基）-苯甲醯胺，獲得2-丁基-3-(2-酮基 -2,3-二氫-1，3-苯并吟唑-6_基）邊唑啉_4(3H)_酮（73%)，為無色固 體：熔點 223-225°C ; 1H NMR (300 MHz，CDC13) 611.97 (s，1H)，8.14 (dd，J = 1.2, 7·9 Hz，1H)，7.88 (dt，J = 1·4, 8·0 Hz，1H)，7.72 (d，J = 7·6 Hz， 1H)，7.59-7.51 (m，2H)，7.32-7.24 (m，2H)，2.39 (t，J = 7.8 Hz，2H)， 1.72-1.60 (m，2H)，1.32-1.18 (m，2H)，0.81 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.6, 158.1，155.4, 148.1，144.4, 135.5, 132.2, 131.7, 127.8, 127.4, 127.2, 125.3, 121.4, 111.5, 110.9, 35.6, 29.1，22.5, 14.6 ; MS (ES+) m/z 336.1 (M + 1). 128409 -170· 200836743 實例22 3-(1Η-苯并三唑-5-基）-2-丁基喹唑啉-4(3H&gt;酮之合成2-Amino-N-(2-keto-2,3-dihydro-1,3-benzop-sal-6- was used according to the procedure as described in Example 1, and irrelevant changes were applied. Replacement of 2-amino-N-(4-methoxy-phenyl)-benzamide with 2-benzamide to give 2-butyl-3-(2-keto-2,3-dihydro - 1,3-benzoxazol-6-yl)-oxazoline-4(3H)-one (73%) as colorless solid: mp 223- 225 ° C; 1H NMR (300 MHz, CDC13) 611.97 ( s, 1H), 8.14 (dd, J = 1.2, 7·9 Hz, 1H), 7.88 (dt, J = 1·4, 8·0 Hz, 1H), 7.72 (d, J = 7·6 Hz, 1H), 7.59-7.51 (m, 2H), 7.32-7.24 (m, 2H), 2.39 (t, J = 7.8 Hz, 2H), 1.72-1.60 (m, 2H), 1.32-1.18 (m, 2H) , 0.81 (t, J = 7·3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.6, 158.1, 155.4, 148.1, 144.4, 135.5, 132.2, 131.7, 127.8, 127.4, 127.2, 125.3, 121.4, 111.5, 110.9, 35.6, 29.1, 22.5, 14.6; MS (ES+) m/z 336.1 (M + 1). 128409 -170 · 200836743 Example 22 3-(1Η-benzotriazol-5-yl)-2- Synthesis of butylquinazoline-4 (3H&gt; ketone

按照如貝例1中所述之程序，且施行無關緊要之改變， 使用5-{[(2-胺基苯基）幾基]胺基卜iH-苯并三峻小羧酸第三-丁 酯置換2-胺基-N-(4-甲氧基-苯基）_苯甲醯胺，獲得3-(1H_苯并 三。坐-5-基）-2-丁基喹唑啉-4(3H)-酮（76%)，為無色固體：熔點 230-232°C ； NMR (300 MHz, CD3OD) 5 8.23 (dd? J = 1.25 7.9 Hz? 1H)，8.14-8.02 (br，2H)，7.98 (dt，J = 1·5, 8·2 Hz，1H)，7.77 (d，J = 7_9 Hz， lH)，7.60-7.47 (m，2H)，2_51(t，J = 7.6Hz，lH)，1.77-1.65 (m，2H)，1.32-1·18 (m，2H)，0.78 (t，J = 7.3 Hz，3H) ; 13C NMR (75 MHz，CD3OD) 5 165.3, 159.9, 149.6, 137.0, 128.9, 128.7, 128.5, 122.5, 37.3, 31.1，24.1， 14.8 ； MS (ES+) m/z 320.0 (M + 1). 實例23 5-(2-丁基_4-酮基4唾。林_3(4H)-基）-1Η-4卜坐-1-緩酸第三-丁酯之 合成According to the procedure as described in Example 1, and the insignificant change was carried out, 5-{[(2-aminophenyl)methylamino]amino-iH-benzotrisuccinic acid was used. Ester replacement of 2-amino-N-(4-methoxy-phenyl)-benzamide to give 3-(1H-benzotris.sodium-5-yl)-2-butylquinazoline- 4(3H)-one (76%) as colorless solid: mp. 230-232 ° C; NMR (300 MHz, CD3OD) 5 8.23 (dd? J = 1.25 7.9 Hz? 1H), 8.14-8.02 (br, 2H) ), 7.98 (dt, J = 1·5, 8·2 Hz, 1H), 7.77 (d, J = 7_9 Hz, lH), 7.60-7.47 (m, 2H), 2_51 (t, J = 7.6Hz, lH), 1.77-1.65 (m, 2H), 1.32-1·18 (m, 2H), 0.78 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CD3OD) 5 165.3, 159.9, 149.6, 137.0, 128.9, 128.7, 128.5, 122.5, 37.3, 31.1, 24.1, 14.8; MS (ES+) m/z 320.0 (M + 1). Example 23 5-(2-butyl-4-keto-4-sodium. Synthesis of _3(4H)-yl)-1Η-4Bus-1-related acid third-butyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用5-{[(2-胺基苯基）羧基]胺基卜1H-吲唑-1-羧酸第三_丁酿置 換2-胺基-N-(4-甲氧基-苯基）-苯曱醯胺，獲得5-(2-丁基-4-酮基 128409 -171 - 200836743 喳唑啉-3(4H)-基）-1Η-啕唑小羧酸第三-丁酯（71%)，為無色固 體：4 NMR (300 MHz，CDC13) ά 8.33 (d，J = 8·8 Hz，1H)，8.24-8.16 (m，2H)，7.76-7.61 (m，3H)，7.45-7.33 (m，2H)，2.37 (t，J = 7.8 Hz，2H)， 1.73-1.57 (m，11H)，1.25-1.10 (m，2H)，0.73 (t，J = 7·3 Hz，3H); 13C NMR (75 MHz，CDC13) 5 162.6, 156.8, 148.7, 147.3, 139.3, 139.1，134.4, 132.8, 128.9, 126.9, 126.8, 126.5, 126.3, 120.9, 120.4, 115.9, 85.4, 35.5, 28.9, 28.0, 22.1, 13.5 ； MS (ES+) m/z 419.0 (M + 1). 實例24 2_丁基-3_(1Η·Ή卜坐·5_基）p奎α坐淋_4(3H)·酮之合成Following the procedure as described in Example 1, and performing an insignificant change, using 5-{[(2-aminophenyl)carboxy]aminopyr 1H-carbazole-1-carboxylic acid 2-Amino-N-(4-methoxy-phenyl)-benzoguanamine afforded 5-(2-butyl-4-keto128409-171 - 200836743 oxazoline-3(4H)- Base -1 - oxazole carboxylic acid tert-butyl ester (71%) as colorless solid: 4 NMR (300 MHz, CDC13) ά 8.33 (d, J = 8 · 8 Hz, 1H), 8.24 - 8.16 (m, 2H), 7.76-7.61 (m, 3H), 7.45-7.33 (m, 2H), 2.37 (t, J = 7.8 Hz, 2H), 1.73-1.57 (m, 11H), 1.25-1.10 (m , 2H), 0.73 (t, J = 7·3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.6, 156.8, 148.7, 147.3, 139.3, 139.1, 134.4, 132.8, 128.9, 126.9, 126.8, 126.5 , 126.3, 120.9, 120.4, 115.9, 85.4, 35.5, 28.9, 28.0, 22.1, 13.5 ; MS (ES+) m/z 419.0 (M + 1). Example 24 2_butyl-3_(1Η·Ή卜坐· 5_base) p-quinone α sitting _4 (3H)·ketone synthesis

按照如實例9中所述之程序，且施行無關緊要之改變， 使用5-(2-丁基-4-酮基p奎唾琳-3(4H)·基）-1Η-4卜坐-1-羧酸第三-丁 酯置換5-(2-丁基-4-酮基喹唑啉_3(4H)_基）-2,3-二氫-1H-啕哚小 羧酸第三-丁 S旨，獲得2-丁基-3-(1Η，唑-5·基）邊唑啉-4(3H)-酮 (97%)，為無色固體：iHNMR (300 MHz，CDC13) δ 11.91-11.22 (br， 1H)，8.32 (d，J = 8·2 Hz，1H)，7.98 (s，1H)，7.82-7.71 (m，2H)，7.55 (d，J = 8.2 Hz，1H)，7.48 (dt，J = 1.5, 8·2 Hz，1H)，7·25 (dd，J = 2·0, 8·2 Hz，1H)， 7.03 (dd，J = 2.0, 8·2 Hz，1H)，2.47-2.37 (m，2H)，1.71-1.57 (m，2H)， 1.25-1.10 (m，2H)，0.72 (t5 J = 7·3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) ά 163.9，157.9，147.9，140.0，135.1，130.2，127.4，127.4，127.1，126.3, 123.6, 120.9, 120.8, 112·1，35.9, 29.6, 22.6, 14.0 ; MS (ES+) m/z 319.0 (M + 1)· 128409 -172- 200836743 實例25 [4-(2-丁基斗酮基喹唑啉-3(4H&gt;基）苯基]脲之合成According to the procedure as described in Example 9, and performing an insignificant change, 5-(2-butyl-4-keto-p-quineline-3(4H)·yl)-1Η-4 -carboxylic acid tert-butyl ester replacement of 5-(2-butyl-4-ketoquinazoline-3(4H)-yl)-2,3-dihydro-1H-indole small carboxylic acid - </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; 11.22 (br, 1H), 8.32 (d, J = 8·2 Hz, 1H), 7.98 (s, 1H), 7.82-7.71 (m, 2H), 7.55 (d, J = 8.2 Hz, 1H), 7.48 (dt, J = 1.5, 8·2 Hz, 1H), 7·25 (dd, J = 2·0, 8·2 Hz, 1H), 7.03 (dd, J = 2.0, 8·2 Hz, 1H) , 2.47-2.37 (m, 2H), 1.71-1.57 (m, 2H), 1.25-1.10 (m, 2H), 0.72 (t5 J = 7·3 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) ά 163.9, 157.9, 147.9, 140.0, 135.1, 130.2, 127.4, 127.4, 127.1, 126.3, 123.6, 120.9, 120.8, 112·1, 35.9, 29.6, 22.6, 14.0; MS (ES+) m/z 319.0 (M + 1)· 128409 -172- 200836743 Example 25 Synthesis of [4-(2-butylbuxenylquinazoline-3(4H&gt;yl)phenyl]urea

將3-(4-胺基苯基）-2-丁基喹唑啉-4(3Η&gt;_ (112毫克，〇·34毫莫 耳）與氰酸鉀（83宅克，1.02亳莫耳）在水/醋酸(2/1 ν/ν) (15 〇毫 升）中之混合物於35。〇下攪拌十六小時，並倒入水（5〇毫升） 中。將碳酸氫鈉溶液慢慢添加至混合物中，直到鹼性為止。 以醋酸乙酯萃取混合物。將有機層以水洗滌，以硫酸鎂脫 水乾燥，及過濾。使濾液在真空中濃縮至乾涸。使殘留物 接受管柱層析，獲得1-[4-(2-丁基-4-酮基喳唑啉-3(4Η&gt;基）苯基] 脲（50毫克’ 44%)，為無色固體：熔點218-221。(： ； WNMRpOO MHz，CDC13) (5 8·24 (dd，J = 1.2, 8.2 Hz，1H)，7.85-7.67 (m，3H)，7·50 (dt，J = 1·2, 8·2 Hz，1H)，7.32 (d，J = 8·8 Hz，2H)，7.07 (d，J = 8·8 Hz，2H)， 4.96 (s，2H)，2.45 (t，J = 7·6 Hz，2H)，1.72-1.59 (m，2H)，1.31-1.17 (m，2H)， 0.80 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz, CDC13) 5 164.1，157.4, 156.1，147.8, 140.4, 135.1，130.6, 127.9, 127.4, 126.9, 126.5, 121.1，120.1， 35.5, 29.1，22.2, 13.7 ; MS (ES+) m/z 337.1 (M + 1)· 實例26 3-(6-胺基吡啶-3-基）-2-丁基喹唑啉-4(3H&gt;酮之合成3-(4-Aminophenyl)-2-butylquinazoline-4 (3Η&gt;_ (112 mg, 〇·34 mmol) with potassium cyanate (83 克, 1.02 亳 Mo) The mixture in water/acetic acid (2/1 ν/ν) (15 mL) was stirred at 35 ° C. for 16 hours and poured into water (5 mL). The sodium bicarbonate solution was slowly added to The mixture was extracted with an ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate, and filtered, and the filtrate was concentrated to dryness in vacuo. 1-[4-(2-Butyl-4-ketooxazoline-3(4Η&gt;yl)phenyl]urea (50 mg '44%) as colorless solid: m.p. 218-221. MHz, CDC13) (5 8·24 (dd, J = 1.2, 8.2 Hz, 1H), 7.85-7.67 (m, 3H), 7·50 (dt, J = 1·2, 8·2 Hz, 1H) , 7.32 (d, J = 8·8 Hz, 2H), 7.07 (d, J = 8·8 Hz, 2H), 4.96 (s, 2H), 2.45 (t, J = 7·6 Hz, 2H), 1.72-1.59 (m, 2H), 1.31-1.17 (m, 2H), 0.80 (t, J = 7·3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 164.1, 157.4, 156.1, 147.8, 140.4 , 135.1 130.6, 127.9, 127.4, 126.9, 126.5, 121.1, 120.1, 35.5, 29.1, 22.2, 13.7; MS (ES+) m/z 337.1 (M + 1) · Example 26 3-(6-Aminopyridin-3-yl Synthesis of 2-butylquinazoline-4 (3H&gt; ketone

-173- 128409 200836743-173- 128409 200836743

使2-丁基-4H-3，1-苯并噚畊斗酮（0.2克，0·99毫莫耳）、2,5-二 胺基外b唆（0.15克，1.29毫莫耳）及峨咬（5毫升）之混合物於11〇 °C下回流6小時。在真空中移除吡啶，並使殘留物接受管柱 層析’而得3-(6-胺基p比咬-3-基）-2-丁基ρ奎唾琳-4(3H)__ (65毫 克，17%)，為無色固體：溶點 162-164°C ; 4 NMR (300 MHz， CDC13) δ 8·23 (dd，J = 1.2, 8·2 Hz，1H)，7.94 (d，J = 2.6 Hz，1H)， 7.78-7.65 (m，2H)，7.43 (dt，J = 1.2, 8·2 Hz，1H)，7·30 (dd，J = 2.6, 8.8 Hz， 1H)，6·62 (d，J = 8·5 Hz，1H)，4.94-4.58 (br，2H)，2.50-2.42 (m，2H)， 1.72-1.59 (m，2H)，1.34-1.20 (m5 2H)，0.82 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz? CDC13) 5 162.8, 158.5, 157.5, 147.4, 147.3, 137.7, 134.6, 127.0, 127.0, 126.6, 124.7, 120.5, 109.0, 35.7, 29.1，22.3, 13.7 ; MS (ES+) m/z 295.0 (M + 1). 實例27 [4-(2-丁基冰酮基喹唑啉_3(4H)_基）苯基]甲基胺基曱酸第三·丁 酯之合成2-butyl-4H-3,1-benzopyrene (0.2 g, 0.99 mmol), 2,5-diamino external b (0.15 g, 1.29 mmol) and A mixture of bites (5 ml) was refluxed at 11 ° C for 6 hours. The pyridine is removed in vacuo and the residue is subjected to column chromatography to give 3-(6-amino-p-buty-3-yl)-2-butyl-p-quinegrin-4(3H)__ ( 65 mg, 17%), as a colorless solid: melting point 162-164 ° C; 4 NMR (300 MHz, CDC13) δ 8·23 (dd, J = 1.2, 8·2 Hz, 1H), 7.94 (d, J = 2.6 Hz, 1H), 7.78-7.65 (m, 2H), 7.43 (dt, J = 1.2, 8·2 Hz, 1H), 7·30 (dd, J = 2.6, 8.8 Hz, 1H), 6 ·62 (d, J = 8·5 Hz, 1H), 4.94-4.58 (br, 2H), 2.50-2.42 (m, 2H), 1.72-1.59 (m, 2H), 1.34-1.20 (m5 2H), 0.82 (t, J = 7·3 Hz, 3H); 13 C NMR (75 MHz? CDC13) 5 162.8, 158.5, 157.5, 147.4, 147.3, 137.7, 134.6, 127.0, 127.0, 126.6, 124.7, 120.5, 109.0, 35.7, 29.1, 22.3, 13.7; MS (ES+) m/z 295.0 (M + 1). Example 27 [4-(2-butyl- </RTI> </RTI> <RTI ID=0.0> Synthesis of aryl butyl citrate

於[4_(2_丁基-4-酮基喹唑啉_3(4H)_基）苯基]胺基曱酸第三·丁 酉曰（100聋:克’ 〇·25宅莫耳）在四氫咬喃（1〇毫升）中之溶液内， 添加氫化鈉（30毫克，〇·75毫莫耳）。將混合物於下攪拌 二十分鐘，接著添加碘甲烷（16微升，〇·25毫莫耳）。將溶液 在裱境溫度下攪拌十六小時，以醋酸乙酯（5〇毫升）稀釋， 以水洗滌，以硫酸鎂脫水乾燥，及過濾。於真空中濃縮濾 128409 -174- 200836743 液。使殘留物接受管柱層析，而得[4-(2-丁基-4-酮基喳唑啉 -3(4H)-基）苯基]甲基胺基甲酸第三-丁酯（8〇毫克，79%)，為無 色固體：4 NMR (300 MHz，CDC13) 5 8.26-8.19 (m，1H)，7.77-7.63 (m，2H)，7·46-7·36 (m，3H)，7.22-7.14 (m，2H)，3.29 (s，3H)，2.42 (t，J = 7·8 Hz，2H)，1.70-1.57 (m，2H)，1.45 (s，9H)，1.31-1.16 (m，2H)，0.80 (t，J = 7.3[4_(2_Butyl-4-ketoquinazolin-3-3(4H)-yl)phenyl]amino decanoic acid · · · 酉曰 (100 聋: 克 ' 〇 · 25 house Moer) Sodium hydride (30 mg, 〇·75 mmol) was added to the solution in tetrahydrogenate (1 mL). The mixture was stirred for twenty minutes, followed by the addition of methyl iodide (16 μL, 〇 25 mmol). The solution was stirred at ambient temperature for 16 hours, diluted with ethyl acetate (5 mL), washed with water, dried over magnesium sulfate and filtered. The solution 128409-174-200836743 was concentrated in vacuo. The residue was subjected to column chromatography to give [4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]methylcarbamic acid tert-butyl ester (8 〇mg, 79%), as a colorless solid: 4 NMR (300 MHz, CDC13) 5 8.26-8.19 (m,1H), 7.77-7.63 (m,2H),7·46-7·36 (m,3H) , 7.22-7.14 (m, 2H), 3.29 (s, 3H), 2.42 (t, J = 7·8 Hz, 2H), 1.70-1.57 (m, 2H), 1.45 (s, 9H), 1.31-1.16 (m, 2H), 0.80 (t, J = 7.3

Hz，3H). 實例28Hz, 3H). Example 28

2-丁基-3-[4_(甲胺基）苯基]4。坐琳-4(3H)__之合成 按照如實例9中所述之程序，且施行無關緊要之改變， 使用[4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]甲基胺基甲酸第 三-丁酯置換5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-2,3-二氫-1H-啕 口木-1-竣酸苐二-丁自曰’獲得2-丁基-3-[4-(甲胺基）苯基]p奎峻p林 -4(3H)·酮（99%)，為無色固體：熔點 121-122。(： ； iHNMR (300 MHz， CDC13) δ 8.25 (dd5 J = 1.2? 8.2 Hz5 1H)3 7.76-7.64 (m? 2H)? 7.41 (dt5 J = 1.2, 8.2 Hz，1H)，7.03-6.97 (m，2H)，6.72-6.65 (m，2H)，4.06-3.89 (br，1H)， 2.87 (s，3H)，2.47 (t，J = 7·6 Hz，2H)，1.7M.59 (m，2H)，1.32-1.18 (m，2H)， 0.80 (t，J = 7.3 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 163.4, 158.7, 150.0, 148.0, 134.6, 129.2, 127.4, 127.2, 126.7, 126.6, 121.2, 113.2, 36.0, 31.0, 29.8, 22.8, 14.1 ; MS (ES+) m/z 308.1 (M + 1). 實例29 3·(4-胺基苯基）-2-甲基p奎峻淋-4(3H)-酮之合成 128409 -175- 2008367432-butyl-3-[4-(methylamino)phenyl]4. Synthesis of sitin-4(3H)__ according to the procedure as described in Example 9, and performing irrelevant changes, using [4-(2-butyl-4-ketoquinazolin-3(4H)) -Phenyl]methyl]methylcarbamic acid tert-butyl ester in place of 5-(2-butyl-4-ketoquinazolin-3(4H)-yl)-2,3-dihydro-1H- Obtaining 2-butyl-3-[4-(methylamino)phenyl]p-kulin p-lin-4(3H)·one (99%) from 啕口木-1-竣酸苐二-丁自曰' , a colorless solid: melting point 121-122. (: ; iHNMR (300 MHz, CDC13) δ 8.25 (dd5 J = 1.2? 8.2 Hz5 1H)3 7.76-7.64 (m? 2H)? 7.41 (dt5 J = 1.2, 8.2 Hz, 1H), 7.03-6.97 (m , 2H), 6.72-6.65 (m, 2H), 4.06-3.89 (br, 1H), 2.87 (s, 3H), 2.47 (t, J = 7·6 Hz, 2H), 1.7M.59 (m, 2H), 1.32-1.18 (m, 2H), 0.80 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 163.4, 158.7, 150.0, 148.0, 134.6, 129.2, 127.4, 127.2, 126.7 , 126.6, 121.2, 113.2, 36.0, 31.0, 29.8, 22.8, 14.1; MS (ES+) m/z 308.1 (M + 1). Example 29 3·(4-Aminophenyl)-2-methylp Synthesis of Junlin-4(3H)-ketone 128409 -175- 200836743

甲基喹唑啉-4(3H)-酮（16%)，為無色固體：熔點216_22〇t： ; i HMethylquinazoline-4(3H)-one (16%) as colorless solid: mp.

7.01-6.95 (m，2H)，6.80-6.74 (m，2H)，4.05-3.70 (br，2H)，2·25 (s，3H); 13 C NMR (75 MHz，CDC13) 6 163.0, 155.6, 147.8, 147.6, 134.8, 129.0, 128-4, 127.4, 127.0, 126.8, 121.2, 116.2, 24.8 ; MS (ES+) m/z 252.0 (M + 1). 實例30 3-(3-胺基苯基&gt;2-甲基喹唑啉_4(3Η)·酮之合成7.01-6.95 (m, 2H), 6.80-6.74 (m, 2H), 4.05-3.70 (br, 2H), 2·25 (s, 3H); 13 C NMR (75 MHz, CDC13) 6 163.0, 155.6, 147.8, 147.6, 134.8, 129.0, 128-4, 127.4, 127.0, 126.8, 121.2, 116.2, 24.8; MS (ES+) m/z 252.0 (M + 1). Example 30 3-(3-Aminophenyl) Synthesis of 2-methylquinazoline-4(3Η)·ketone

按照如實例2中所述之程序，且施行無關緊要之改變， 使用2-甲基-4H-3，1-苯并啰畊冰酮置換2-丁基-4H-3，1-苯并呤畊 -4-酮，獲得3-(3-胺基苯基）-2-甲基喳唑啉_4(3H)_酮（27%)，為無 色固體：熔點 201-203°C ; 1H NMR (300 MHz，CDC13) 5 8.24 (dd，J =1.2, 8·2 Hz，1H)，7.73 (dt，J = 1.2, 8·2 Hz，1H)，7_64 (d，J = 8·2 Hz, 1H)， 7.43 (dt，J = 1.2, 8·2 Hz，1H)，7·26 (t，J = 7·9 Hz，1H)，6.77-6.71 (m，1H)， 6.60-6.55 (m，1H)，6.50 (t，J = 2.0 Hz，1H)，3.99-3.70 (br，2H)，2.27 (s， 3H) ; 13C NMR (75 MHz, CDC13) 5 162.6, 154·8, 148.6, 147.8, 139.0, 134.8, 131.0, 127.4, 127.0, 126.9, 121.1，117.7, 116.2, 114.5, 24·5 ; MS 128409 -176- 200836743 (ES+) m/z 252.0 (Μ + 1). 實例31Displacement of 2-butyl-4H-3,1-benzoxanthene with 2-methyl-4H-3,1-benzoxanthine according to the procedure as described in Example 2 and subject to insignificant changes Tr. 4-ketone to give 3-(3-aminophenyl)-2-methyloxazoline-4(3H)-one (27%) as colorless solid: m.p.: 201-203 ° C; 1H NMR (300 MHz, CDC13) 5 8.24 (dd, J = 1.2, 8·2 Hz, 1H), 7.73 (dt, J = 1.2, 8·2 Hz, 1H), 7_64 (d, J = 8·2 Hz, 1H), 7.43 (dt, J = 1.2, 8·2 Hz, 1H), 7·26 (t, J = 7·9 Hz, 1H), 6.77-6.71 (m, 1H), 6.60-6.55 (m, 1H), 6.50 (t, J = 2.0 Hz, 1H), 3.99-3.70 (br, 2H), 2.27 (s, 3H); 13C NMR (75 MHz, CDC13) 5 162.6, 154·8, 148.6, 147.8, 139.0, 134.8, 131.0, 127.4, 127.0, 126.9, 121.1, 117.7, 116.2, 114.5, 24·5 ; MS 128409 -176- 200836743 (ES+) m/z 252.0 (Μ + 1). Example 31

3-(4-胺基苯基&gt;2_戊基喳唑啉4(3H&gt;_之合成 按照如實例2中所述之程序，且施行無關緊要之改變，Synthesis of 3-(4-aminophenyl)-2-pentyloxazoline 4 (3H&gt;_ according to the procedure as described in Example 2, and irrelevant changes were performed,

使用2-戊基-4H-3，1-苯并嘮畊冰酮置換2-丁基-4H-3，1-苯并崎畊 斗酮，及1，4-苯二胺置換苯二胺，獲得3·…胺基苯基）_2_ 戊基峻唆琳-4(3H)-酮（50%)，為無色固體：熔點178-18(rc ; 1 H NMR (300 MHz，CDC13) (5 8.24 (dd，J = 1.2, 8·2 Hz，1H)，7.76-7.65 (m， 2H)，7.42 (dt，J = 1.2, 8·2 Hz，1H)，7.00-6.94 (m，2H)，6.80-6.73 (m，2H)， 4.07-3.70 (br，1H)，2.45 (t，J = 7·6 Hz，2H)，1.73-1.59 (m，2H)，1.27-1.14 (m，4H)，0.81 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 3 163.2, 158·6, 147.5, 134.7, 129.3, 127.9, 127.4, 127.2, 126.7, 121.1，116.1，36.2, 31.8, 27.3，22.6，14.2 ; MS (ES+) m/z 308.0 (M + 1)· 實例32 [2-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]胺基甲酸第三-丁酯之 合成Replacement of 2-butyl-4H-3,1-benzoxanone with 2-pentyl-4H-3,1-benzopyrene, and phenylenediamine with 1,4-phenylenediamine, Obtained 3·...aminophenyl)_2_pentyl junyl-4(3H)-one (50%) as colorless solid: m.p. 178-18 (rc; 1 H NMR (300 MHz, CDC13) (5 8.24 (dd, J = 1.2, 8·2 Hz, 1H), 7.76-7.65 (m, 2H), 7.42 (dt, J = 1.2, 8·2 Hz, 1H), 7.00-6.94 (m, 2H), 6.80 -6.73 (m, 2H), 4.07-3.70 (br, 1H), 2.45 (t, J = 7·6 Hz, 2H), 1.73-1.59 (m, 2H), 1.27-1.14 (m, 4H), 0.81 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 3 163.2, 158·6, 147.5, 134.7, 129.3, 127.9, 127.4, 127.2, 126.7, 121.1, 116.1, 36.2, 31.8, 27.3 , 22.6, 14.2; MS (ES+) m/z 308.0 (M + 1) · Example 32 [2-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]amino Synthesis of tert-butyl formate

128409 -177- 200836743 按照如實例1中所述之程序，且施行無關緊要之改變， 使用（2-{[(2-胺基苯基）幾基]胺基}苯基）胺基甲酸第三_丁酯置 換2-胺基-N-(4-甲氧基_苯基苯甲醯胺，獲得[2-(2-丁基-4-酮基 喳唑啉-3(4H)-基）苯基]胺基甲酸第三—丁酯（97%)，為無色固 體：4 NMR (300 MHz，CDC13) 5 8.23 (dd，J = 8.2, 1.2 Hz，1H)，8.05 (d，J = 8·2 Hz，1H)，7.80-7.67 (m，2H)，7.50-7.42 (m，2H)，7·20 (td，J = 7.9, 1·5 Hz，1H)，7.08 (dd，J = 7·9, 1.5 Hz，1H)，6.34 (s，1H)，2.38 (t，J = 7.6 Hz，2H)，1.66-1.51 (m，2H)，1.39 (s，9H)，1.29-1.13 (m，2H)，0.77 (t，J = 7.3, 3H)· 實例33 3-(2-胺基苯基）-2-丁基π奎唾琳-4(3H)-_之合成128409-177-200836743 According to the procedure as described in Example 1, and irrelevant changes were made, using (2-{[(2-aminophenyl))amino]phenyl}amino)carboxylic acid _Butyl ester replaces 2-amino-N-(4-methoxy-phenylbenzamide to give [2-(2-butyl-4-ketooxazoline-3(4H)-yl) Phenyl] carbamic acid tert-butyl ester (97%) as colorless solid: 4 NMR (300 MHz, CDC13) 5 8.23 (dd, J = 8.2, 1.2 Hz, 1H), 8.05 (d, J = 8 · 2 Hz, 1H), 7.80-7.67 (m, 2H), 7.50-7.42 (m, 2H), 7·20 (td, J = 7.9, 1·5 Hz, 1H), 7.08 (dd, J = 7 · 9, 1.5 Hz, 1H), 6.34 (s, 1H), 2.38 (t, J = 7.6 Hz, 2H), 1.66-1.51 (m, 2H), 1.39 (s, 9H), 1.29-1.13 (m, 2H), 0.77 (t, J = 7.3, 3H) · Example 33 Synthesis of 3-(2-aminophenyl)-2-butyl π quinidine-4(3H)-_

按照如實例9中所述之程序，且施行無關緊要之改變， 使用[2-(2-丁基-4-_基夺唾淋-3(4H)-基）苯基]胺基甲酸第三-丁 酯置換5-(2-丁基-4-酮基喳唑啉-3(4H)-基）-2,3-二氫-1H-吲哚-1-羧酸第三丁酯，獲得3-(2-胺基苯基）-2-丁基喳唑啉-4(3H)-S同 (68%)，為無色固體：1H NMR (300 MHz，CDC13) 5 8.26 (dd，J = 1.2, 8.2 Hz，1H)，7.79-7.68 (m，2H)，7.44 (dt，J = 1.2, 8·2 Hz，1H)，7.27 (dt，J = 1.2, 8.2 Hz，1H)，7.01 (dd，J = 1·5，8·2 Hz，1H)，6.92-6.85 (m，2H)， 3.72-3.57 (br*，2H)，2.50-2.41 (m，2H)，1.73-1.61 (m，2H)，1.32-U8 (m， 2H)，0.79 (t，J = 7.3 Hz, 3H); 13 C NMR (75 MHz，CDC13) 5 161.9, 158.2, 147.6, 142.8, 134.6, 130.4, 128.9, 127.1，127.0, 126.6, 123.2, 120.6, 119.5, 128409 -178- 200836743 117.2, 34.9, 28.8, 22.3, 13·7 ; MS (ES+) m/z 294.0 (Μ + 1). 實例34 [5-(2-丁基-4-酮基喹唑啉·3(4Η)_基）吡啶-2-基]胺基甲酸第三-丁 酯之合成According to the procedure as described in Example 9, and performing an insignificant change, [2-(2-butyl-4-yl-pyloryl-3(4H)-yl)phenyl]carbamic acid was used as the third -butyl butyrate to replace tert-butyl 5-(2-butyl-4-ketooxazoline-3(4H)-yl)-2,3-dihydro-1H-indole-1-carboxylate 3-(2-Aminophenyl)-2-butyloxazoline-4(3H)-S, (68%), as a colorless solid: 1H NMR (300 MHz, CDC13) 5 8.26 (dd,J = 1.2, 8.2 Hz, 1H), 7.79-7.68 (m, 2H), 7.44 (dt, J = 1.2, 8·2 Hz, 1H), 7.27 (dt, J = 1.2, 8.2 Hz, 1H), 7.01 (dd , J = 1·5,8·2 Hz, 1H), 6.92-6.85 (m, 2H), 3.72-3.57 (br*, 2H), 2.50-2.41 (m, 2H), 1.73-1.61 (m, 2H ), 1.32-U8 (m, 2H), 0.79 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 161.9, 158.2, 147.6, 142.8, 134.6, 130.4, 128.9, 127.1, 127.0 , 126.6, 123.2, 120.6, 119.5, 128409 -178- 200836743 117.2, 34.9, 28.8, 22.3, 13·7 ; MS (ES+) m/z 294.0 (Μ + 1). Example 34 [5-(2-butyl Synthesis of -4-ketoquinazoline·3(4Η)-yl)pyridin-2-yl]carbamic acid tert-butyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用（5-{[(2-胺基苯基）羰基]胺基}吡啶-2-基）胺基甲酸第三-丁 酯置換2-胺基-Ν-(4-甲氧基-苯基）-苯甲醯胺，獲得[5-(2-丁基冰 酮基喹唑啉-3(4印-基 &gt;比啶-2-基]胺基甲酸第三-丁醋（77%)，為 無色固體：4 NMR (300 MHz，CDC13) (5 8.54 (s，1H)，8.27-8.14 (m， 3H)，7.79-7.66 (m，2H)，7.57 (dd，J = 8.8, 2·6 Hz，1H)，7.45 (td，J = 8.2, 1·5 Hz，1H)，2.43 (t，J = 7.6 Hz，2H)，1.71-1.50 (m，11H)，1.50 (s，9H)， 1.30-1.17 (m，2H)，0.82 (t，J = 7.3, 3H). 實例35 [(第二-丁氧幾基）胺基]{[4_(2_丁基冰酮基邊σ坐琳_3(册)_基）苯 基]胺基}亞甲基]胺基甲酸第三丁酯之合成Using a procedure as described in Example 1 and applying an insignificant change, the use of (5-{[(2-aminophenyl)carbonyl]amino}pyridin-2-yl)carbamic acid tert-butyl ester Displacement of 2-amino-indole-(4-methoxy-phenyl)-benzamide to give [5-(2-butylrhosylquinazoline-3) (4-im-yl) 2-yl]aminocarbamic acid tert-butyl vinegar (77%) as colorless solid: 4 NMR (300 MHz, CDC13) (5 8.54 (s, 1H), 8.27-8.14 (m, 3H), 7.79- 7.66 (m, 2H), 7.57 (dd, J = 8.8, 2·6 Hz, 1H), 7.45 (td, J = 8.2, 1·5 Hz, 1H), 2.43 (t, J = 7.6 Hz, 2H) , 1.71-1.50 (m, 11H), 1.50 (s, 9H), 1.30-1.17 (m, 2H), 0.82 (t, J = 7.3, 3H). Example 35 [(2nd-butoxy)amine Synthesis of the base [{4_(2_butyl ketone ketone side σ sitting _3 (book) _ yl) phenyl] amino} methylene] carbamic acid tert-butyl ester

於3-(4_胺基-苯基）_2_丁基-3Hw奎唾4 -4-1同（120毫克，0.41毫 莫耳）、二醯亞胺基硫基三碳酸0,0-二-第三_丁酯（113毫克， 0.41耄莫耳）及吡啶（〇12毫升，143毫莫耳）在N，N_二甲基甲 添加氣化汞（0.33毫 酷胺（2毫升）中之混合物内，在〇°C下， 128409 -179- 200836743 克，〇·49毫莫耳），並擾拌。將所形成之混合物在〇°C下攪拌 20分鐘，以醋酸乙酯稀釋，及過濾。將濾液以水洗滌，以 石瓜S文鈉脫水乾燥，且過濾。在真空中濃縮濾液。使殘留物 接文官柱層析’而得K第三-丁氧羰基）胺基]{[4_(2-丁基_4•酮基 心坐p林_3(4H)-基）苯基]胺基}亞甲基]胺基甲酸第三_丁酯（138 毫克，63%)，為無色固體：iHNMR (3〇〇 MHz，CDCy 5 8·22 ㈣， J = 8.2, 1.5 Hz，1H)，7.86-7.78 (m，2H)，7.76-7.63 (m，2H)，7·41 (td，J = 7.9, 1·5 Hz，1H)，7.21-7.13 (m，2H)，2·42 (t，J = 7.8 Hz，2H)，1.72-1.59 (m， 2H)，1.52 (s，9H)，1.49 (s，9H)，1.34-1.20 (m，2H)，0.81 (t，J = 7·3 Hz，3H). 實例36 l-[4-(2-丁基-4-酮基喹唑啉·3(4Η&gt;基）苯基]胍之合成3-(4-Amino-phenyl)_2-butyl-3Hw quinavirin-4-4-1 with (120 mg, 0.41 mmol), diindolimidothiotricarbonate 0,0-di - a third butyl ester (113 mg, 0.41 Torr) and pyridine (〇 12 ml, 143 mmol) added with vaporized mercury (0.33 milamine (2 mL) in N,N-dimethyl In the mixture, at 〇 ° C, 128409 -179 - 200836743 grams, 〇 · 49 millimoles), and disturbed. The resulting mixture was stirred at 〇 ° C for 20 min, diluted with ethyl acetate and filtered. The filtrate was washed with water, dried with a sodium sulphate and filtered. The filtrate was concentrated in vacuo. The residue is subjected to chromatography on the column to obtain K-tris-butoxycarbonyl)amino]{[4_(2-butyl-4)ketone-based p-line_3(4H)-yl)phenyl] Amino-methylene]carbamic acid tert-butyl ester (138 mg, 63%) as colorless solid: iHNMR (3 〇〇 MHz, CDCy 5 8·22 (d), J = 8.2, 1.5 Hz, 1H) , 7.86-7.78 (m, 2H), 7.76-7.63 (m, 2H), 7.41 (td, J = 7.9, 1.5 Hz, 1H), 7.21 - 7.13 (m, 2H), 2·42 ( t, J = 7.8 Hz, 2H), 1.72-1.59 (m, 2H), 1.52 (s, 9H), 1.49 (s, 9H), 1.34-1.20 (m, 2H), 0.81 (t, J = 7· 3 Hz, 3H). Example 36 Synthesis of l-[4-(2-butyl-4-ketoquinazoline·3(4Η&gt;yl)phenyl]indole

按照如實例9中所述之程序，且施行無關緊要之改變， 使用[(弟二-丁氧幾基）胺基]-{[4-(2-丁基-4-S同基ρ奎唾琳-3(4Η)_ 基）苯基]胺基}亞甲基]胺基甲酸第三-丁 g旨置換5_(2-丁基冰酮 基p奎唑p林-3(4H)-基）-2,3-二氫-1H-吲嗓-1-羧酸第三-丁酯，獲得 1-[4-(2-丁基冰酮基喳唑啉-3(4H)-基）苯基]胍（71%)，為無色固 體：熔點 208-210°C ; 1H NMR (300 MHz，CD3 OD) (5 8.27-8.22 (m，1H)， 7.90 (dt，J - 1.2, 8.2 Hz，1H)，7.79-7.75 (m，1H)，7.62-7.51 (m，5H)，2.56 (t， J = 7.9 Hz，2H)，1.80-1.69 (m，2H)，1.40-1.24 (m，2H)，0.88 (t，J = 7.3 Hz， 3H) ; 13C NMR (75 MHz，CD3OD) 6 165.4, 159.4, 159.2, 149.7, 138.5, 138.4，137.1，132.4，129.2，128.9，128.8，128.5，122.3, 37.4, 31.0, 24.1， 14.8 ； MS (ES+) m/z 335.9 (M + 1). 128409 -180- 200836743 實例37 2 丁基3 (4確基节基）峻唾p林·4(扭)__之合成According to the procedure as described in Example 9, and carrying out irrelevant changes, [(4-di-butoxy)amino]-{[4-(2-butyl-4-S-iso-p-quinone琳-3(4Η)_yl)phenyl]amino}methylene]aminocarbamic acid third-butyryl substituted 5_(2-butylrhosyl p-pyrazole p-lin-3(4H)-yl a tert-butyl ester of -2,3-dihydro-1H-indole-1-carboxylic acid to give 1-[4-(2-butylhryl oxazoline-3(4H)-yl)benzene Base 胍(71%), as colorless solid: mp 208-210 ° C; 1H NMR (300 MHz, CD3 OD) (5 8.27-8.22 (m, 1H), 7.90 (dt, J - 1.2, 8.2 Hz, 1H), 7.79-7.75 (m, 1H), 7.62-7.51 (m, 5H), 2.56 (t, J = 7.9 Hz, 2H), 1.80-1.69 (m, 2H), 1.40-1.24 (m, 2H) , 0.88 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CD3OD) 6 165.4, 159.4, 159.2, 149.7, 138.5, 138.4, 137.1, 132.4, 129.2, 128.9, 128.8, 128.5, 122.3, 37.4, 31.0, 24.1, 14.8 ; MS (ES+) m/z 335.9 (M + 1). 128409 -180- 200836743 Example 37 2 Butyl 3 (4 arginyl) 唾 唾 p · · · · 4 4 4 _ synthesis

按照如貫例2中所述之程序，且施行無關緊要之改變Follow the procedure described in Example 2 and perform irrelevant changes

基）p奎峻琳-4(3H)_酮（32〇/〇)，為黃色固體：熔點116_117。〇; iHNMR (300 MHz，CDC13) 5 8·27 (dd，J = 1·4, 7.9 Hz，1H)，8.21-8.16 (m，2H)， 7.76 (dt，J = 1·5, 8.2 Hz，1H)，7.67 (d，J = 7.6 Hz，1H)，7.47 (dt，J = 1.5, 8.2 Hz，1H)，7.36-7.30 (m，2H)，5.47 (s，2H)，2.68 (t，J = 7.3 Hz，2H), 1.82-1.71 (m，2H)，1.46-1.32 (m，2H)，0.90 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz， CDC13) 6162.4，156.5，147.4，147.3，143·6，134.7，127.2，127.0，126.8, 124.2, 120.1，46.1，35.0, 29·2, 22·4, 13.8 ; MS (ES+) m/z 338.0 (M + 1)· 實例38 3-(4-胺基苄基）-2-丁基4唑琳-4(3H)-酮之合成P) Kujunlin-4(3H)-one (32〇/〇), as a yellow solid: mp. 116_117. H; iHNMR (300 MHz, CDC13) 5 8·27 (dd, J = 1·4, 7.9 Hz, 1H), 8.21-8.16 (m, 2H), 7.76 (dt, J = 1. 5, 8.2 Hz, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.47 (dt, J = 1.5, 8.2 Hz, 1H), 7.36-7.30 (m, 2H), 5.47 (s, 2H), 2.68 (t, J = 7.3 Hz, 2H), 1.82-1.71 (m, 2H), 1.46-1.32 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 6162.4, 156.5, 147.4, 147.3, 14·6, 134.7, 127.2, 127.0, 126.8, 124.2, 120.1, 46.1, 35.0, 29·2, 22·4, 13.8; MS (ES+) m/z 338.0 (M + 1)· Example 38 Synthesis of 3-(4-Aminobenzyl)-2-butyl-4-oxalin-4(3H)-one

按照如製備IB中所述之程序’且施行無關緊要之改變， 使用2-丁基_3_(4-硝基芊基）喳唑啉·4(3Η)-酮置換N-(4-甲氧基-苯基）-2-硝基苯甲醯胺，並縮短反應時間至兩小時，於管柱 層析純化後，獲得3-(4-胺基爷基）-2-丁基4唾琳-4(3H)-酮 (81%)，為無色固體：熔點 151-154°C ; WNMRpOOMHz’CDCU) 128409 -181 - 200836743 5 8.27 (dd，J = 1.4, 7·9 Hz，1H)，7.70 (dt，J = 1.5, 7.9 Hz，1H)，7.63 (d，J =7.3 Hz，1H)，7.42 (dt，J = 1.5, 7.9 Hz，1H)，7.01-6.95 (m，2H)，6.62-6.56 (m5 2H)，5.27 (s，2H)，4.04-2.92 (br，2H)，2.76 (t，J = 7.3 Hz, 2H)，1.78-1.67 (m，2H)，1.46-1.32 (m，2H)，0.90 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz， CDC13) 5 162.6, 157.7, 147.3, 145.9, 134.2, 127.9, 127.0, 126.8, 126.3, 126.0, 120.4, 115.3, 46.1，35.0, 29.5, 22.5, 13·8 ; MS (ES+) m/z 308.0 (M + 1)· 實例39 l_[4-(2-丁基-4-酮基喳唑啉-3(4H&gt;基）苯基]-3-氰胍之合成Displacement of N-(4-methoxyl) with 2-butyl-3-(4-nitroindenyl)oxazoline·4(3Η)-one according to the procedure described in Preparation IB and performing irrelevant changes Base-phenyl)-2-nitrobenzamide, and shorten the reaction time to two hours, after column chromatography purification, to obtain 3-(4-amino-based)-2-butyl 4 salicin -4(3H)-one (81%) as a colorless solid: m.p.: 151 - 154 ° C; WNMR pOOMHz 'CDCU) 128409 -181 - 200836743 5 8.27 (dd, J = 1.4, 7·9 Hz, 1H), 7.70 (dt, J = 1.5, 7.9 Hz, 1H), 7.63 (d, J = 7.3 Hz, 1H), 7.42 (dt, J = 1.5, 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.62 6.56 (m5 2H), 5.27 (s, 2H), 4.04-2.92 (br, 2H), 2.76 (t, J = 7.3 Hz, 2H), 1.78-1.67 (m, 2H), 1.46-1.32 (m, 2H) ), 0.90 (t, J = 7·3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.6, 157.7, 147.3, 145.9, 134.2, 127.9, 127.0, 126.8, 126.3, 126.0, 120.4, 115.3, 46.1, 35.0, 29.5, 22.5, 13·8; MS (ES+) m/z 308.0 (M + 1) · Example 39 l_[4-(4-butyl-4-ketooxazoline-3 (4H&gt; Synthesis of phenyl)-3-cyanoguanidine

於3-(4-胺基-苯基）-2-丁基-3H-p奎嗤琳-4-自同（120毫克，0.41毫 莫耳）與水（5毫升）之混合物中，慢慢添加鹽酸（1〇%，2.0毫 升）’並檟:拌，直到溶液變成透明為止。於此溶液中添加納 二氰基胺（150毫克，1.76毫莫耳）在水（2.0毫升）與醋酸（3毫 升）中之溶液。將所形成之混合物於環境溫度下擾拌兩天， 且倒入水（100毫升）中。以醋酸乙酯萃取混合物，將有機層 以水洗滌，以硫酸鎂脫水乾燥，及過濾。在真空中濃縮遽 液。使殘留物自醋酸乙酯再結晶，獲得1-[4-(2-丁基-4-酮基口奎 唾淋-3(4H)-基）苯基]-3-氰脈（102毫克，69%)，為無色固體：、j：容 點 223-226°C ; 1H NMR (300 MHz，DMSO-d6 ) 5 9.25 (s，1H)，8.06 (dd， J - 1.2，7.9 Hz，1H)，7.80 (dt，J = 1.7，8.8 Hz，1H)，7.64 (d，J = 8.2 Hz， 1H)，7.54-7.44 (m，3H)，7.35-7.29 (m，2H)，7.13 (s，2H)，2.32 (t，J = 7·3 Hz， 128409 -182- 200836743 2H)，1·64·1·52 (m，2H)，1_25-1.11 (m，2H), 0·75 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz，DMSO_d6) 6 162.0, 159.8, 157.5, 147.6，139.0, 135.0, 132.7, 129.5, 127.3, 126.8, 126.7, 121.8, 120.8, 117.4, 35.2, 28.6, 22.0, 14.1 ； MS (ES+) m/z 361.0 (M + 1). 實例40In a mixture of 3-(4-amino-phenyl)-2-butyl-3H-p-quineline-4-self (120 mg, 0.41 mmol) and water (5 mL), slowly Add hydrochloric acid (1%, 2.0 ml) and mix: until the solution becomes clear. A solution of sodium dicyanamide (150 mg, 1.76 mmol) in water (2.0 ml) and acetic acid (3 ml) was added to this solution. The resulting mixture was scrambled at ambient temperature for two days and poured into water (100 mL). The mixture was extracted with ethyl acetate, the organic layer was washed with water, dried over magnesium sulfate and filtered. Concentrate the mash in a vacuum. The residue was recrystallized from ethyl acetate to give 1-[4-(2-butyl-4-keto-phenoxy-ylidene-3(4H)-yl)phenyl]-3-cyanide (102 mg, 69%), as a colorless solid: j: 223-226 ° C; 1H NMR (300 MHz, DMSO-d6) 5 9.25 (s, 1H), 8.06 (dd, J - 1.2, 7.9 Hz, 1H) , 7.80 (dt, J = 1.7, 8.8 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.54-7.44 (m, 3H), 7.35-7.29 (m, 2H), 7.13 (s, 2H) ), 2.32 (t, J = 7·3 Hz, 128409 -182- 200836743 2H), 1·64·1·52 (m, 2H), 1_25-1.11 (m, 2H), 0·75 (t, J = 7·3 Hz, 3H); 13C NMR (75 MHz, DMSO_d6) 6 162.0, 159.8, 157.5, 147.6, 139.0, 135.0, 132.7, 129.5, 127.3, 126.8, 126.7, 121.8, 120.8, 117.4, 35.2, 28.6, 22.0, 14.1 ; MS (ES+) m/z 361.0 (M + 1). Example 40

3-(4-胺基-2,5-二氯苯基）-2-丁基峻e坐琳-4(3H)-_之合成 按照如實例2中所述之程序，且施行無關緊要之改變， 使用2,5-二氯-1，4-苯二胺置換ΐ，3·苯二胺，獲得3-(4-胺基-2,5-二 氯苯基）-2-丁基喳唑啉-4(3H)-酮（13%)，為無色固體：熔點 108-110°C ； 'HNMR (300 MHz, CDC13) 5 8.25 (dd5 J = 1.7? 8.2 Hz? 1H)? 7·79-7·67 (m，2H)，7.44 (dt，J = 1.7, 8.2 Hz，1H)，7.18 (s，1H)，6.92 (s，1H)， 4.40 (s，2H)，2.45-2.36 (m，2H)，1.79-1.61 (m，2H)，1.37-1.21 (m，2H)，0.85 (t? J = 7.3 Hz? 3H) ； 13C NMR (75 MHz5 CDC13) δ 162.5, 157.5, 147.8, 145.3, 135.0, 132.0, 130.5, 127.5, 127.0, 125.0, 120.8, 118.1，116·3, 35.3, 29.0, 22.7，14.1 ; MS (ES+) m/z 362.0 (Μ + 1). 實例41Synthesis of 3-(4-Amino-2,5-dichlorophenyl)-2-butyljune-Salina-4(3H)-_ according to the procedure as described in Example 2, and with irrelevant changes, Substitution of ruthenium, 3·phenylenediamine with 2,5-dichloro-1,4-phenylenediamine to give 3-(4-amino-2,5-dichlorophenyl)-2-butyloxazoline -4(3H)-one (13%) as colorless solid: m.p. 108-110 ° C; 'HNMR (300 MHz, CDC13) 5 8.25 (dd5 J = 1.7? 8.2 Hz? 1H)? 7·79-7 · 67 (m, 2H), 7.44 (dt, J = 1.7, 8.2 Hz, 1H), 7.18 (s, 1H), 6.92 (s, 1H), 4.40 (s, 2H), 2.45-2.36 (m, 2H ), 1.79-1.61 (m, 2H), 1.37-1.21 (m, 2H), 0.85 (t? J = 7.3 Hz? 3H); 13C NMR (75 MHz5 CDC13) δ 162.5, 157.5, 147.8, 145.3, 135.0, 132.0, 130.5, 127.5, 127.0, 125.0, 120.8, 118.1, 116·3, 35.3, 29.0, 22.7, 14.1; MS (ES+) m/z 362.0 (Μ + 1). Example 41

3-(4-胺基-2,5-二甲基苯基）_2-丁基喹唑啉·4(3Η)·酮之合成 按照如實例2中所述之程序， 且施行無關緊要之改變， 128409 -183 - 200836743 使用2,5-一甲基-1，4-本一胺置換l，3-苯二胺，獲得&gt;(4-胺基_2,5-二甲基苯基）-2-丁基喹唑啉_4(3H)_酮（48%)，為無色固體：熔 點 162-165°C ; 1 H NMR (300 MHz，CDC13) 6 8.26 (d，J = 8.2 Hz，1H)， 7.77-7.65 (m，2H)，7.42 (dt，J = 1.7, 8·2 Hz，1H)，6.78 (s，1H)，6.63 (s，1H)， 3.95-3.51 (br，2H)，2.39 (t，J = 7_6 Hz，2H)，2.13 (s，3H)，1.95 (s，3H)， 1.74-1.61 (m，2H)，1.33-1.19 (m，2H)，0.81 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.7, 158.6, 148.0, 145.7, 134.6, 133.9, 129.9, 127.4, 127.2，127.0，126.6，121.4，121.1，117.3, 35.4, 29.3, 22.7，17.5，17.3, 14.1 ； MS (ES+) m/z 322.0 (M + 1). 實例42 3-(4-胺基-2,3,5,6-四甲基苯基）-2-丁基峻σ坐琳-4(3H)-酮之合成Synthesis of 3-(4-Amino-2,5-dimethylphenyl)_2-butylquinazoline·4(3Η)·one was carried out according to the procedure described in Example 2, and irrelevant changes were performed. , 128409 -183 - 200836743 Replacement of 1,3-phenylenediamine with 2,5-monomethyl-1,4-monoamine to obtain &gt;(4-amino-2,5-dimethylphenyl) 2-Butylquinazoline _4(3H)-one (48%) as colorless solid: mp 162-165 ° C; 1 H NMR (300 MHz, CDC13) 6 8.26 (d, J = 8.2 Hz, 1H), 7.77-7.65 (m, 2H), 7.42 (dt, J = 1.7, 8·2 Hz, 1H), 6.78 (s, 1H), 6.63 (s, 1H), 3.95-3.51 (br, 2H) , 2.39 (t, J = 7_6 Hz, 2H), 2.13 (s, 3H), 1.95 (s, 3H), 1.74-1.61 (m, 2H), 1.33-1.19 (m, 2H), 0.81 (t, J = 7·3 Hz, 3H) ; 13C NMR (75 MHz, CDC13) 5 162.7, 158.6, 148.0, 145.7, 134.6, 133.9, 129.9, 127.4, 127.2, 127.0, 126.6, 121.4, 121.1, 117.3, 35.4, 29.3, 22.7,17.5,17.3, 14.1; MS (ES+) m/z 322.0 (M + 1). Example 42 3-(4-Amino-2,3,5,6-tetramethylphenyl)-2-butyl Synthesis of σ sitin-4(3H)-ketone

按照如實例2中所述之程序，且施行無關緊要之改變， 使用2,3,5,6-四甲基-1，4-苯二胺置換1，3-苯二胺，獲得3-(4-胺基 -2,3,5,6-四甲基苯基）-2-丁基喹唑淋-4(3H)-酮（39%)，為無色固 體：4 NMR (300 MHz，CDC13) δ 8.27 (d，J = 7.9 Hz，1H)，7.78-7.68 (m，2H)，7.43 (dt，J = 1.2, 8.2 Hz，1H)，3.94-3.54 (br，2H)，2.26 (t，J = 7.6 Hz，2H)，2.12 (s，6H)，1.90 (s，6H)，1.72-1.60 (m，2H)，1.33-1.19 (m，2H)， 0.82 (t，J = 7·3 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.5, 158.9, 143.7, 134.6, 131.0, 127.6, 127.3, 126.9, 126.6, 121.1，119.5, 34.9, 28.8, 22.8，15.4，14.3，14.2 ; MS (ES+) m/z 350.3 (M + 1). 實例43 128409 •184- 200836743Following the procedure as described in Example 2, and carrying out irrelevant changes, the replacement of 1,3-phenylenediamine with 2,3,5,6-tetramethyl-1,4-phenylenediamine gave 3-( 4-Amino-2,3,5,6-tetramethylphenyl)-2-butylquinazolin-4(3H)-one (39%) as colorless solid: 4 NMR (300 MHz, CDC13 ) δ 8.27 (d, J = 7.9 Hz, 1H), 7.78-7.68 (m, 2H), 7.43 (dt, J = 1.2, 8.2 Hz, 1H), 3.94-3.54 (br, 2H), 2.26 (t, J = 7.6 Hz, 2H), 2.12 (s, 6H), 1.90 (s, 6H), 1.72-1.60 (m, 2H), 1.33-1.19 (m, 2H), 0.82 (t, J = 7·3 Hz , 3H); 13C NMR (75 MHz, CDC13) 5 162.5, 158.9, 143.7, 134.6, 131.0, 127.6, 127.3, 126.9, 126.6, 121.1, 119.5, 34.9, 28.8, 22.8, 15.4, 14.3, 14.2; MS (ES+ m/z 350.3 (M + 1). Example 43 128409 •184- 200836743

4-(2-丁基-4-酮基喹唑啉_3(4Η)·基）苯曱腈之合成 3-(4-溴苯基）-2-丁基喳唑啉-4(3Η)-酮（200毫克，0.56毫莫耳）、 碘化鉀（186毫克，1·12毫莫耳）、氰化鈉（137毫克，28毫莫 耳）、Ν，Ν-二甲基乙二胺（0.12毫升，112毫莫耳）及曱苯（5 〇毫 升）之混合物係經由使氮起泡二十分鐘而被脫氣，接著添加 蛾化銅（I) (107毫克，0.56毫莫耳）。使所形成之混合物回流 二十五小時。將氫氧化銨（5毫升）添加至反應混合物中，並 於環境溫度下再持續攪拌一小時，且添加水（2〇毫升）。以 醋酸乙酯萃取混合物，將有機層以水洗滌，以硫酸鎂脫水 乾燥，及過濾。在真空中濃縮濾液。使殘留物接受管柱層 析，獲得4-(2-丁基-4-酮基喳唑啉-3(4Η)·基）苯甲腈（186毫克， 44%)，為無色固體：1H NMR (300 MHz，CDC13) 5 8.23 (dd，J = 1.2, 8·2 Hz，1H)，7·89-7·83 (m，2H)，7.78 (dt，J = 1.2, 8·2 Hz，1H)，7.70 (d，J = 7.3 Hz，1H)，7·47 (dt，J = 1.2, 8·2 Hz，1H)，7.43-7.38 (m，2H)，2·36 (t，J = 7·6 Hz，2H), 1.71-1.59 (m，2H)，1.31-1.18 (m，2H)，0.80 (t，J = 7.3 Hz， 3H) ; 13C NMR (75 MHz，CDC13) 5 162.5, 155.9, 147.7, 141.9, 135.3, 134.0, 130.1，127.6，127.3，127.3，120.7，118.1，113.8, 35.9, 29.3, 22.6, 14.0 ； MS (ES+) m/z 304.3 (M + 1). 實例44 2-丁基-3-吡啶-4·基喳唑啉-4(3H)-酮之合成 128409 -185- 200836743Synthesis of 4-(2-butyl-4-ketoquinazoline-3(4Η)-yl)benzonitrile 3-(4-bromophenyl)-2-butyloxazoline-4(3Η) -ketone (200 mg, 0.56 mmol), potassium iodide (186 mg, 1.12 mmol), sodium cyanide (137 mg, 28 mmol), hydrazine, hydrazine-dimethylethylenediamine (0.12) A mixture of milliliters (112 millimoles) and toluene (5 milliliters) was degassed by bubbling nitrogen for twenty minutes, followed by the addition of molybdenum (I) (107 mg, 0.56 mmol). The resulting mixture was refluxed for twenty-five hours. Ammonium hydroxide (5 ml) was added to the reaction mixture, and stirring was continued for an additional hour at ambient temperature, and water (2 mL) was added. The mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography to give 4-(2-butyl-4-ketooxazoline-3(4Η)yl)benzonitrile (186 mg, 44%) as colorless solid: 1H NMR (300 MHz, CDC13) 5 8.23 (dd, J = 1.2, 8·2 Hz, 1H), 7·89-7·83 (m, 2H), 7.78 (dt, J = 1.2, 8·2 Hz, 1H ), 7.70 (d, J = 7.3 Hz, 1H), 7·47 (dt, J = 1.2, 8·2 Hz, 1H), 7.43-7.38 (m, 2H), 2·36 (t, J = 7 · 6 Hz, 2H), 1.71-1.59 (m, 2H), 1.31-1.18 (m, 2H), 0.80 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.5, 155.9, 147.7, 141.9, 135.3, 134.0, 130.1, 127.6, 127.3, 127.3, 120.7, 118.1, 113.8, 35.9, 29.3, 22.6, 14.0; MS (ES+) m/z 304.3 (M + 1). Example 44 2-butyl Synthesis of -3-pyridin-4·yloxazoline-4(3H)-one 128409 -185- 200836743

按照如貫例2中所述之程序，且施行無關緊要之改變， 使用4-胺基吡啶置換i，3_苯二胺，獲得2•丁基斗吡啶斗基喹唑 淋·4(3Η)_酮（22%)，為無色固體：熔點128_13(rc ; 1hnmr (獅 MHz? CDC13) 5 8.85 (br5 2H)5 8.23 (dd? J = 1.7) 8.2 Hz5 1H)5 7.81-7.67 (m, 2H)? 7.47 (dt? J =： l.2? 7.9 Hz5 1H)? 7.28-7.22 (m5 2H)? 2.38 (t5 J = 7.6According to the procedure as described in Example 2, and the insignificant change was made, the i-phenyldiamine was replaced with 4-aminopyridine to obtain 2·butylpyridinyl quinazoline·4(3Η). Ketone (22%) as a colorless solid: m.p.: </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> ) 7.47 (dt? J =: l.2? 7.9 Hz5 1H)? 7.28-7.22 (m5 2H)? 2.38 (t5 J = 7.6

Hz，2H)，1.72-1.59 (m，2H)，1.31-1.17 (m5 2H)，0.80 (t，J = 7·3 Hz，3H); C NMR (75 MHz，CDC13) 5 162.2, 155.7, 152.0, 147.6, 145.8, 135.3, 127.5, 127.3, 127.3, 124.1，120.7, 35.8, 29.4, 22.6, 14.0 ; MS (ES+) m/z 280.2 (M + 1). 實例45 2_丁基各(6-甲氧基峨σ定_3_基 &gt;奎唾琳_4(3h)__之合成Hz, 2H), 1.72-1.59 (m, 2H), 1.31-1.17 (m5 2H), 0.80 (t, J = 7·3 Hz, 3H); C NMR (75 MHz, CDC13) 5 162.2, 155.7, 152.0 , 147.6, 145.8, 135.3, 127.5, 127.3, 127.3, 124.1, 120.7, 35.8, 29.4, 22.6, 14.0; MS (ES+) m/z 280.2 (M + 1). Example 45 2_butyl each (6-A) Synthesis of oxindole _3_base&gt; quetialine _4(3h)__

按)^如實例2中所述之程序，且施行無關緊要之改變， 使用5-胺基-2-甲氧基吡啶置換ι，3-苯二胺，獲得2_丁基_3_(6_ 甲氧基外I：咬-3-基 &gt;奎唾琳-4(3H)-酮（28%)，為無色固體：溶點 100-103°C ; 1H NMR (300 MHz，CDC13) δ 8.23 (dd，J = 1.7, 8.2 Hz，1H)， 8.05 (d，J = 2.9 Hz，1H)，7.79-7.66 (m，2H)，7.48-7.41 (m，2H)，6·90 (d，J = 9.0 Hz，1H)，3.99 (s，3H)，2.47-2.38 (m，2H)，1.73-1.58 (m，2H)，1.34-U9 (m，2H)，0.81 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) (5 164.1， 128409 -186- 200836743 162.7, 157.0, 147.4, 146.1，138.6, 134.7, 127.5, 127.1，127·0, 126.7, 120.4, 111.9, 54.0, 35·6, 29.0, 22.3, 13·7 ; MS (ES+) m/z 310.2 (Μ + 1). 實例46 [4-(2-丁基-4-酮基喳唑啉-3(4Η)-基）爷基]胺基甲酸第三-丁酯之 合成According to the procedure described in Example 2, and irrelevant changes were made, replacing iota, 3-phenylenediamine with 5-amino-2-methoxypyridine to obtain 2_butyl_3_(6_A Oxyl group I: -3-yl group &gt; quetialine-4(3H)-one (28%), colorless solid: melting point 100-103 ° C; 1H NMR (300 MHz, CDC13) δ 8.23 ( Dd, J = 1.7, 8.2 Hz, 1H), 8.05 (d, J = 2.9 Hz, 1H), 7.79-7.66 (m, 2H), 7.48-7.41 (m, 2H), 6.90 (d, J = 9.0 Hz, 1H), 3.99 (s, 3H), 2.47-2.38 (m, 2H), 1.73-1.58 (m, 2H), 1.34-U9 (m, 2H), 0.81 (t, J = 7·3 Hz , 3H); 13 C NMR (75 MHz, CDC13) (5 164.1, 128409 -186-200836743 162.7, 157.0, 147.4, 146.1, 138.6, 134.7, 127.5, 127.1, 127·0, 126.7, 120.4, 111.9, 54.0, 35·6, 29.0, 22.3, 13·7 ; MS (ES+) m/z 310.2 (Μ + 1). Example 46 [4-(2-butyl-4-ketooxazoline-3(4Η)- Synthesis of tert-butyl carbamic acid

按照如實例1中所述之程序，且施行無關緊要之改變， 使用（4-{[(2-胺基苯基）羰基]胺基}芊基）胺基曱酸第三-丁酯置 換2-胺基-Ν-(4-甲氧基-苯基）-苯甲醯胺，獲得[4-(2-丁基冰酮基 喹唑啉-3(4H)-基）芊基]胺基甲酸第三-丁酯（89%)，為無色固 體：熔點 113-115°C ; iHNMRpOOMHiCDsOD) 5 8.20(dd，J=1.7, 8.2 Hz，1H)，7·87 (dt，J 二 1.7, 8.2 Hz，1H)，7.76-7.71 (m，1H)，7.58-7.51 (m，3H), 7.35 (d，J = 8·2 Hz，2H)，4.37 (s，2H)，2.49 (t，J = 7.6 Hz，2H)， 1.75-1.62 (m，2H)，1.50 (s，9H)，1.34-1.20 (m，2H)，0.83 (t，J = 7.3 Hz， 3H) ; 13 C NMR (75 MHz，CD3OD) 5 165.0, 160.1，159.3, 149.6, 143.5, 138.0, 136.8, 130.5, 130.3, 128.7, 128.5, 128.4, 122.4, 8U，45.4, 37.1， 31.1，29.5, 24.1，14·7 ; MS (ES+) m/z (%) 408.3 (M + 1). 實例47 3-[4-(胺基曱基）苯基]-2-丁基喹唑啉-4(3H)__之合成Following the procedure as described in Example 1, and performing an insignificant change, using (4-{[(2-aminophenyl)carbonyl)amino}indenyl) amide decanoic acid tert-butyl ester 2 -Amino-indole-(4-methoxy-phenyl)-benzamide, obtaining [4-(2-butylrhosylquinazolin-3(4H)-yl)indenyl]amine Third-butyl carboxylic acid ester (89%) as colorless solid: m.p.: 113-115°C; iHNMRpOOMHiCDsOD) 5 8.20 (dd, J=1.7, 8.2 Hz, 1H), 7·87 (dt, J 2 1.7, 8.2 Hz, 1H), 7.76-7.71 (m, 1H), 7.58-7.51 (m, 3H), 7.35 (d, J = 8·2 Hz, 2H), 4.37 (s, 2H), 2.49 (t, J = 7.6 Hz, 2H), 1.75-1.62 (m, 2H), 1.50 (s, 9H), 1.34-1.20 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CD3OD) 5 165.0, 160.1, 159.3, 149.6, 143.5, 138.0, 136.8, 130.5, 130.3, 128.7, 128.5, 128.4, 122.4, 8U, 45.4, 37.1, 31.1, 29.5, 24.1, 14·7 ; MS (ES+) m /z (%) 408.3 (M + 1). Example 47 Synthesis of 3-[4-(aminomercapto)phenyl]-2-butylquinazoline-4(3H)__

按照如實例9中所述之程序，且施行無關緊要之改變， 128409 -187- 200836743 使用[4-(2-丁基-4-酮基喳唑啉-ΜΗ)-基）爷基]胺基甲酸第三-丁 酉曰置換5·(2·丁基-4-g同基p奎嗤琳-3(4H)-基）-2,3-二氫-1H-吲嗓小 魏酸第三-丁酯，獲得3-[4-(胺基甲基）苯基]-2-丁基喳唑啉 -4(3H)·酮（88%)，為蠟狀固體：iHNMR (3〇〇 MHz，CD3〇D)占 8 21 (dd，J = 1.7, 8.2 Hz，1H)，7·87 (dt，J = 1.7, 8.2 Hz, 1H)，7.76-7.72 (m，1H)， 7·64·7_51 (m，3H)，7.39-7.33 (m，2H)，3.90 (s，2H)，2.50 (t，J = 7·6 Hz，2H)， 1.74-1.63 (m，2H)，1.34-1.21 (m，2H)，0.84 (t，J = 7_3 Hz，3H) ; 13C NMR (75 MHz，CD3OD) (5 164.2，159.3，148·8，145.1，137.2，136.0，129.8, 129.8, 127.9, 127.7, 127.6, 121.6, 46.2, 36.4, 30.3, 23.3, 13.9 ; MS (ES+) m/z 308.3 (M + 1). 實例48 3-(l，3-苯并二氧伍圜烯_5_基）丁基喳唑啉_4(3H)_酮之合成According to the procedure as described in Example 9, and irrelevant changes were made, 128409-187-200836743 using [4-(2-butyl-4-ketooxazoline-oxime)-yl)-ylamino Formic acid third-butyrene replacement 5·(2·butyl-4-g synthyl p-quineline-3(4H)-yl)-2,3-dihydro-1H-indole small Wei acid third- Butyl ester gave 3-[4-(aminomethyl)phenyl]-2-butyloxazoline-4(3H).one (88%) as a waxy solid: iHNMR (3 〇〇 MHz, CD3〇D) occupies 8 21 (dd, J = 1.7, 8.2 Hz, 1H), 7·87 (dt, J = 1.7, 8.2 Hz, 1H), 7.76-7.72 (m, 1H), 7·64·7_51 (m, 3H), 7.39-7.33 (m, 2H), 3.90 (s, 2H), 2.50 (t, J = 7·6 Hz, 2H), 1.74-1.63 (m, 2H), 1.34-1.21 (m , 2H), 0.84 (t, J = 7_3 Hz, 3H); 13C NMR (75 MHz, CD3OD) (5 164.2, 159.3, 148·8, 145.1, 137.2, 136.0, 129.8, 129.8, 127.9, 127.7, 127.6, 121.6, 46.2, 36.4, 30.3, 23.3, 13.9; MS (ES+) m/z 308.3 (M + 1). Example 48 3-(l,3-benzodioxanthene-5-yl)butylhydrazine Synthesis of oxazoline_4(3H)-one

按照如實例2中所述之程序，且施行無關緊要之改變， 使用苯并[d][U]二氧伍圜烯-5-胺置換1，3-苯二胺，獲得3-(1，3-苯并二氧伍圜烯-5-基&gt;2-丁基喳唑啉-4(3H)-酮（15%)，為無色 固體：熔點 125-126°C ; 4 NMR (300 MHz，CDC13) 5 8.24 (dd，J = 1.7, 8·2 Hz，1H)，7·77-7_65 (m，2H)，7.43 (dt，J = 1.7, 8·2 Hz，1H)， 6.94-6.89 (m9 1H)? 6.71-6.66 (m? 2H), 6.09 (d5 J = 1.2 Hz, 1H)? 6.04 (d? J = 1.2 Hz，1H)，2·47 (t，J = 7·6 Hz，2H)，1.74-1.62 (m，2H)，1.35-1.20 (m，2H)， 0.83 (t，J = 7.3 Hz，3H)· 13C NMR (75 MHz，CDC13) 5 163.0, 157.6, 149.0, 148.6, 147.7, 134.8, 131.1，127.4, 127.3, 126.9, 122.1，121.0, 109.5, 128409 -188- 200836743 109.2, 102·4, 35.7, 29.7, 22.7, 14·1 ; MS (ES+) m/z 323.3 (Μ + 1). 實例49 3-(5-胺基答-1-基）-2-丁基4唾p林-4(3H)-酮之合成Following the procedure as described in Example 2, and carrying out an insignificant change, 1,3-phenylenediamine was replaced with benzo[d][U]dioxolan-2-amine to give 3-(1, 3-benzodioxanthene-5-yl&gt; 2-butyloxazoline-4(3H)-one (15%) as colorless solid: m.p. 125-126°C; 4 NMR (300 MHz , CDC13) 5 8.24 (dd, J = 1.7, 8·2 Hz, 1H), 7·77-7_65 (m, 2H), 7.43 (dt, J = 1.7, 8·2 Hz, 1H), 6.94-6.89 (m9 1H)? 6.71-6.66 (m? 2H), 6.09 (d5 J = 1.2 Hz, 1H)? 6.04 (d? J = 1.2 Hz, 1H), 2·47 (t, J = 7·6 Hz, 2H), 1.74-1.62 (m, 2H), 1.35-1.20 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H) · 13C NMR (75 MHz, CDC13) 5 163.0, 157.6, 149.0, 148.6, 147.7, 134.8, 131.1, 127.4, 127.3, 126.9, 122.1, 121.0, 109.5, 128409 -188- 200836743 109.2, 102·4, 35.7, 29.7, 22.7, 14·1 ; MS (ES+) m/z 323.3 (Μ + 1). Example 49 Synthesis of 3-(5-Amino-l-yl)-2-butyl 4 salivin-4(3H)-one

按照如實例2中所述之程序，且施行無關緊要之改變， 使用莕-1,5-二胺置換1，3-苯二胺，獲得3-(5-胺基莕小基）-2-丁基 喹唑啉-4(3H)-酮（25%)，為無色固體：熔點151-152°C ; iHNMR (300 MHz，CDC13) 5 8.29 (d，J = 8.5 Hz, 1H)，7.92 (d，J = 8.5 Hz，1H)， 7.83-7.74 (m，2H)，7.55-7.43 (m，2H)，7.39 (dd，J = 0.9, 7.3 Hz，1H)，7.20 (d, J = 7.3 Hz，1H)，6.82 (d，J = 8·5 Hz，1H)，6.74 (d，J = 7.3 Hz，1H)， 4.76-3.57 (br，2H)，2_29 (t，J = 7.6 Hz，2H)，1.68-1.55 (m，2H)，U9-1.04 (m，2H)，0.68 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz, CDC13) 5 162.9, 158.3, 148.1，143.4, 134.9, 134.5, 131.4, 128.8, 127.5, 127.4, 126.9, 126.8, 125.1，124.5, 123.2, 121.1，112.5, 110.9, 35.4, 29.7, 22.5, 14.0 ; MS (ES+) m/z 344.2 (M + 1). 實例50 2-丁基-3-(6-酮基-1，6-二氫吡啶-3_基 &gt;奎唑啉·4(3Η)_酮之合成Following the procedure as described in Example 2, and carrying out irrelevant changes, 1,3-phenylenediamine was replaced with 荇-1,5-diamine to give 3-(5-aminoindolyl)-2- Butylquinazoline-4(3H)-one (25%) as colorless solid: m.p.: 151-152°C; iHNMR (300 MHz, CDC13) 5 8.29 (d, J = 8.5 Hz, 1H), 7.92 ( d, J = 8.5 Hz, 1H), 7.83-7.74 (m, 2H), 7.55-7.43 (m, 2H), 7.39 (dd, J = 0.9, 7.3 Hz, 1H), 7.20 (d, J = 7.3 Hz , 1H), 6.82 (d, J = 8·5 Hz, 1H), 6.74 (d, J = 7.3 Hz, 1H), 4.76-3.57 (br, 2H), 2_29 (t, J = 7.6 Hz, 2H) , 1.68-1.55 (m, 2H), U9-1.04 (m, 2H), 0.68 (t, J = 7·3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.9, 158.3, 148.1, 143.4 , 134.9, 134.5, 131.4, 128.8, 127.5, 127.4, 126.9, 126.8, 125.1, 124.5, 123.2, 121.1, 112.5, 110.9, 35.4, 29.7, 22.5, 14.0; MS (ES+) m/z 344.2 (M + 1) Example 50 Synthesis of 2-Butyl-3-(6-keto-1,6-dihydropyridin-3-yl) quinazoline·4(3Η)-one

於2-丁基-3-(6-甲氧基吡啶-3-基 &gt;奎唑啉-4(3Η)-酮（58毫克， 〇·19毫莫耳）在乙腈（10.0毫升）與二氯甲烷（10.0毫升）中之溶 128409 -189- 200836743 液内，在0°C下，添加蛾化鈉（57毫克，0.38毫莫耳）、氯基 三甲基矽烷（0.049毫升，〇·38毫莫耳）及水（0·001毫升）。將所 形成之混合物於65°C下攪拌五小時，接著緩慢添加亞硫酸 納溶液（5%，20毫升）。以醋酸乙酯（3 X 5〇毫升）萃取混合物。 使合併之有機層以無水硫酸鈉脫水乾燥，及過濾。在真空 中/辰細濾液。使殘留物以醋酸乙g旨再結晶，獲得2_丁基_3_(6_ 酮基-1，6-二氫吡啶-3-基 &gt;奎唑啉-4(3H)-酮（40毫克，71%)，為無 色固體· 點 &gt;260 C，1 H NMR (300 MHz，CDC13) 5 13.42-12.99 (br， 1H)，8.23 (dd，卜 1.2, 7.9 Hz，1H)，7·77 (dt，J = 1.4, 8·2 Hz，1H)，7.68 (d， J = 8.2 Hz，1H)，7.46 (dt，J = 1.2, 8.2 Hz，1H)，7.40-7.31 (m，2H)，6.73 (d， J - 9.4 Hz，1H)，2.59-2.50 (m，2H)，1.77-1.64 (m，2H)，1.42-1.28 (m，2H)， 0.89 (t? J = 7.3 Hz? 3H) ； MS (ES+) m/z 296.2 (M + 1). 實例51 2·丁基-3-(1-氧化吡啶冰基 &gt;奎唑啉，犯)·酮之合成To 2-butyl-3-(6-methoxypyridin-3-yl) quinazoline-4(3Η)-one (58 mg, 〇19 mmol) in acetonitrile (10.0 mL) with In a solution of chloromethane (10.0 ml), 128409 -189-200836743, at 0 ° C, add sodium moth (57 mg, 0.38 mmol), chlorotrimethyl decane (0.049 ml, 〇·38) Millol) and water (0.001 ml). The resulting mixture was stirred at 65 ° C for five hours, then slowly added sodium sulfite solution (5%, 20 mL). Ethyl acetate (3 X 5) The mixture was extracted with MgSO4. The combined organic layers were dried over anhydrous sodium sulfate and filtered, and then filtered and evaporated to dryness in vacuo. The residue was recrystallized from ethyl acetate to afford 2- _ _ _ _ _ _ ketone Base-1,6-dihydropyridin-3-yl&gt; quinazoline-4(3H)-one (40 mg, 71%) as a colorless solid, &lt; 260 C, 1 H NMR (300 MHz, CDC13) 5 13.42-12.99 (br, 1H), 8.23 (dd, Bu 1.2, 7.9 Hz, 1H), 7·77 (dt, J = 1.4, 8·2 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.46 (dt, J = 1.2, 8.2 Hz, 1H), 7.40-7.31 (m, 2H), 6.73 (d, J - 9.4 Hz, 1H), 2.59-2.50 (m, 2H), 1.77-1.64 (m, 2H), 1.42-1.28 (m, 2H), 0.89 (t? J = 7.3 Hz? 3H) ; MS (ES+) m /z 296.2 (M + 1). Example 51 2·Butyl-3-(1-oxidized pyridyl yl) &gt; quinazoline, s.

於2-丁基-3-(吡啶冰基）p奎唑啉-4(3H)_酮（47毫克，〇17毫莫 耳）在二氣甲烷（1〇毫升）中之溶液内，在〇。〇下，添加尿素過 氧化氫加成化合物（79毫克，〇·84毫莫耳）與三氟醋酸酐（〇12 宅升，0.84耄莫耳）。將混合物於環境溫度下攪拌四小時。 添加更多二氣曱烷（30毫升）。將此溶液以飽和碳酸氫鈉溶 液洗滌，以無水硫酸鈉脫水乾燥，及過濾。在真空中濃縮 濾液。使殘留物接受管柱層析（在醋酸乙酯中之2%曱醇）， 128409 -190- 200836743 獲得2-丁基-3-(1-氧化吡啶-4-基）喳唑啉-4(3H)-酮（12毫克， 24%)，為無色固體：熔點 163-168°C ; 1HNMR(300 MHz，CDC13) 5 8.33 (d，J = 7·3 Hz，2H)，8.22 (dd，J = 1_4, 8·2 Hz，1H)，7.78 (dt，J = 1.4, 8.2 Hz，1H)，7.69 (d，J = 7·6 Hz，1H)，7·48 (dt，J = 1.4, 8·2 Hz，1H)，7.20 (d，J = 7·3 Hz，2H)，2.44 (t，J = 7·6 Hz，2H)，1.74-1.61 (m，2H)，1.36-1.21 (m，2H)，0.85 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 6 162.3, 155.5, 147.6, 141.0, 135.5, 134.7, 127.7, 127.6, 127.3, 127.0, 120.5, 35.9, 29.3, 22.7, 14.1 ; MS (ES+) m/z 296.2 (M + 1). 實例52 [4-(2-丁基-4-酮基喳峻啉-3(4H)-基）-2_(三氟甲基）苯基]胺基甲 酸第三-丁酯之合成In a solution of 2-butyl-3-(pyridyl)pyrazoline-4(3H)-one (47 mg, 〇17 mmol) in di-methane (1 mL) . Under the armpit, add urea hydrogen peroxide addition compound (79 mg, 〇·84 mmol) with trifluoroacetic anhydride (〇12 liter, 0.84 耄mol). The mixture was stirred at ambient temperature for four hours. Add more dioxane (30 ml). This solution was washed with a saturated sodium hydrogencarbonate solution, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. Column chromatography (2% decyl alcohol in ethyl acetate), 128409 - 190 - 200836743 afforded 2-butyl-3-(1- oxapyridin-4-yl)oxazoline-4 ( 3H)-ketone (12 mg, 24%) as colorless solid: m.p. 163 - 168 C; 1HNMR (300 MHz, CDC13) 5 8.33 (d, J = 7.3 Hz, 2H), 8.22 (dd, J = 1_4, 8·2 Hz, 1H), 7.78 (dt, J = 1.4, 8.2 Hz, 1H), 7.69 (d, J = 7·6 Hz, 1H), 7·48 (dt, J = 1.4, 8 · 2 Hz, 1H), 7.20 (d, J = 7·3 Hz, 2H), 2.44 (t, J = 7·6 Hz, 2H), 1.74-1.61 (m, 2H), 1.36-1.21 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 6 162.3, 155.5, 147.6, 141.0, 135.5, 134.7, 127.7, 127.6, 127.3, 127.0, 120.5, 35.9, 29.3 , 22.7, 14.1; MS (ES+) m/z 296.2 (M + 1). Example 52 [4-(2-butyl-4-ketosulfonyl-3(4H)-yl)-2. Synthesis of methyl-phenyl]aminocarboxylic acid tert-butyl ester

按照如實例1中所述之程序，且施行無關緊要之改變， 使用[4-{[(2-胺基苯基）幾基]胺基}-2·(三氟甲基）苯基]胺基甲 酸第三-丁酯置換2-胺基-N-(4-甲氧基-苯基）_苯甲醯胺，獲得 [4-(2-丁基-4-酮基喹唑啉-3(4H)_基）-2_(三氟甲基）苯基]胺基甲 酸第三-丁酯（100%)，為無色固體：MS (ES+) m/z 462.3 (M + 1). 實例53[4-{[(2-Aminophenyl)methyl]amino}-2.(trifluoromethyl)phenyl]amine was used according to the procedure as described in Example 1 and insignificantly changed. Replacement of 2-amino-N-(4-methoxy-phenyl)-benzimidamide with a third-butyl carboxylic acid to obtain [4-(2-butyl-4-ketoquinazolin-3) (4H)-yl)-2-(trifluoromethyl)phenyl]carbamic acid tert-butyl ester (100%) as colorless solid: MS (ES+) m/z 462.3 (M + 1).

3-[4-胺基-3-(三氟甲基）本基]-2-丁基峻σ坐p林_4(3H)_酮之合成 128409 -191 - 200836743Synthesis of 3-[4-amino-3-(trifluoromethyl)benyl]-2-butyl sigma sylvestre _4(3H) ketone 128409 -191 - 200836743

使用[4-(2-丁基冬酉同基口奎唾琳_3(卿基p仁氣甲基）苯基]胺 基甲酸第三-丁酯置換5_(2_丁基斗酮基喹唑啉-3(4H)_基）_2,3_二Displacement of 5-(2-butylidene quinolidine) with [4-(2-butylindole) with the base of the quinine _3 (Qingji p-nuclear methyl) phenyl] carbamic acid tert-butyl ester Oxazoline-3(4H)-yl)_2,3_two

基]-2-丁基峻嗤琳-4(3H)__ (55%)，為無色固體：熔點143-144 C » H NMR (300 MHz, CDC13) δ 8.23 (d5 J = 8.2 Hz, 1H)? 7.78-7.65 (m，2H)，7.44 (dt，J = 1.4, 8·2 Hz，1H)，7.29 (d，J = 2.3 Hz，1H)，7·15 (dd， J - 2.3, 8·4 Hz，1H)，6.85 (d，J = 8·4 Hz，1H)，4.41 (s，2H)，2.43 (t，J = 7.6 Hz，2H)，1.72-1.60 (m，2H)，1.34-1.20 (m，2H)，0·81 (t，J = 7·3 Hz，3H); 13C NMR (75 MHz，CDC13) 5 163.2，157.9，147.7，145.6，135.0，133.1， 127.4，127.0，127.0，126.9，126.4，122.8，120.9，118.6，114.6 (q)，35.9, 29.6, 22.7, 14.1 ； MS (ES+) m/z 362.3 (M + 1). 實例54 [4-(2-丁基-4-酮基峻唆琳_3(4H)-基）-3-(三氟甲基）苯基]胺基甲 酸第三·丁 i旨之合成] -2- -2- ( -4 (3H)__ (55%), as a colorless solid: melting point 143-144 C » H NMR (300 MHz, CDC13) δ 8.23 (d5 J = 8.2 Hz, 1H)? -7.65 (m, 2H), 7.44 (dt, J = 1.4, 8·2 Hz, 1H), 7.29 (d, J = 2.3 Hz, 1H), 7·15 (dd, J - 2.3, 8·4 Hz , 1H), 6.85 (d, J = 8·4 Hz, 1H), 4.41 (s, 2H), 2.43 (t, J = 7.6 Hz, 2H), 1.72-1.60 (m, 2H), 1.34-1.20 ( m, 2H), 0·81 (t, J = 7·3 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 163.2, 157.9, 147.7, 145.6, 135.0, 133.1, 127.4, 127.0, 127.0, 126.9, </ RTI> <RTIgt; Synthesis of 唆3_4(4H)-yl)-3-(trifluoromethyl)phenyl]aminocarboxylic acid

Ν Η 按照如實例1中所述之程序，且施行無關緊要之改變， 使用[4-{[(2-胺基苯基）幾基]胺基卜3_(三氟甲基）苯基]胺基甲 酸第三-丁酯置換2-胺基-N_(4_甲氧基-苯基）_苯曱醯胺，獲得 [4-(2-丁基-4-酮基p奎唆1淋-3(4H)-基）-3-(三氣曱基）苯基]胺基曱 酸第三-丁酯（100%)，為無色固體：MS (ES+) m/z 462·3 (Μ + Ο 128409 -192- 200836743 實例55 3·[4-胺基_2-(三氟甲基）苯基]_2_丁基喳唑啉·4(3h),之合成Ν Η [4-{[(2-Aminophenyl))ylamino)-3-(trifluoromethyl)phenyl]amine was used according to the procedure as described in Example 1, and irrelevant changes were applied. Replacement of 2-amino-N-(4-methoxy-phenyl)-benzoguanamine with a third-butyl carboxylic acid to obtain [4-(2-butyl-4-keto-p-quinone-1)- 3(4H)-yl)-3-(trimethylsulfonyl)phenyl]amino decanoic acid tert-butyl ester (100%) as colorless solid: MS (ES+) m/z 462·3 (Μ + Ο 128409 -192- 200836743 Example 55 3·[4-Amino-2-(trifluoromethyl)phenyl]_2-butyloxazoline·4(3h), synthesis

按照如實例9中所述之程序，且施行無關緊要之改變， 使用[4-(2-丁基冰酮基喳唑琳_3(4H)_基）-3-(三氟甲基）苯基]胺 f 基甲酸苐二-丁酯置換5-(2-丁基-4-國基4嗅淋-3(4H)-基）-2,3-二 氫-1H-啕哚小羧酸第三-丁酯，獲得3-[4_胺基冬(三氟曱基）苯 基]-2-丁基π奎唾琳-4(3H)-_ (55%)，為無色固體：溶點173-174 °C ； !H NMR (300 MHz? CDC13) δ 8.24 (d5 J = 8.2 Hz, 1H), 7.79-7.65 (m，2H)，7.47-7.40 (m，1H)，7.07-7.01 (m，2H)，6.91 (dd，J = 2.3, 8.4 Hz， 1H)，4.36-3.80 (br，2H)，2.57-2.22 (m，2H)，1_83_1.59 (m，2H)，1.38-U7 (m，2H)，0.83 (t，J = 7·3 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 163·1， 158.1，148.1，134.9, 132.0, 127.4, 127.3, 126·9, 125.0, 121.4, 120.7, 118.8, k 113.7 (q)，35·4, 29.3, 22.7, 14·1 ; MS (ES+) m/z 362.3 (Μ + 1). 實例56 [4-(2_丁基-4-酮基吡啶[2,3-d]嘧啶-3(4H)-基）苯基]胺基曱酸第三 -丁酯之合成According to the procedure as described in Example 9, and carrying out irrelevant changes, [4-(2-butyl-fatracarbazide- 3(4H)-yl)-3-(trifluoromethyl)benzene Substituted 5-(4-butyl-4-yl 4 olfactory-3(4H)-yl)-2,3-dihydro-1H-indole carboxylic acid Third-butyl ester, 3-[4-amino-(trifluoromethyl)phenyl]-2-butyl π-quineline-4(3H)-- (55%) was obtained as a colorless solid: dissolved Point 173-174 °C; !H NMR (300 MHz? CDC13) δ 8.24 (d5 J = 8.2 Hz, 1H), 7.79-7.65 (m, 2H), 7.47-7.40 (m, 1H), 7.07-7.01 ( m, 2H), 6.91 (dd, J = 2.3, 8.4 Hz, 1H), 4.36-3.80 (br, 2H), 2.57-2.22 (m, 2H), 1_83_1.59 (m, 2H), 1.38-U7 ( m, 2H), 0.83 (t, J = 7·3 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 163·1, 158.1, 148.1, 134.9, 132.0, 127.4, 127.3, 126·9, 125.0 , 121.4, 120.7, 118.8, k 113.7 (q), 35·4, 29.3, 22.7, 14·1 ; MS (ES+) m/z 362.3 (Μ + 1). Example 56 [4-(2_butyl- Synthesis of 4-ketopyridine [2,3-d]pyrimidin-3(4H)-yl)phenyl]amino decanoic acid tert-butyl ester

將2-胺基菸鹼酸（0.19克，1.36毫莫耳）與戊酸酐（3毫升，過 量）混合，並於130°C下回流六小時。在高真空下移除過量 128409 • 193 - 200836743 戊酸酐，而得油性產物。將4_胺基苯基胺基甲酸第三-丁酯 (0.20克，2.58耄莫耳）與吡啶（5 〇毫升）添加至上述油性產物 中。使所形成之混合物在丨⑺^下回流六小時。於真空中移 除吡啶。使殘留物接受管柱層析（在己烷中之33%醋酸乙 酯）’獲得[4-(2-丁基-4·酮基吡啶p，3_d]嘧啶-3(餅基体基]胺基 甲酸第三-丁酯，為無色固體（〇 〇82克，15%): lHNMR(3〇〇MHz， CDC13) 8.97 (dd，J = 4.5, 2.1 Hz，1H)，8.58 (dd，J = 7.8, 2.1 Hz，1H)， 7·55 (d，J = 8·4 Hz，2H)，7.39 (dd，J = 7.8, 4·5 Hz，1H)，7_14 (d，J = 8.4 Hz， 2H)，6.77 (s，1H)，2.46 (t，J = 7.5 Hz，2H)，1.83-1.72 (m，2H)，1.53 (s，9H)， 1.35-1.20 (m，2H)，0.81 (t，J = 7·5 Hz，3H) ; MS (ES+) m/z 395.2 (M + 1). 實例572-Aminonicotinic acid (0.19 g, 1.36 mmol) was mixed with valeric anhydride (3 mL, excess) and refluxed at 130 ° C for six hours. Excess 128409 • 193 - 200836743 valeric anhydride was removed under high vacuum to give an oily product. 4-Iminophenylphenylcarbamic acid tert-butyl ester (0.20 g, 2.58 mmol) and pyridine (5 mL) were added to the above oily product. The resulting mixture was refluxed for six hours under hydrazine (7). The pyridine was removed in vacuo. The residue was subjected to column chromatography (33% ethyl acetate in hexane) to give [4-(2-butyl-4. ketopyridine p,3~d)pyrimidine-3 (cake base) amine group. Tri-butyl formate, colorless solid (〇〇 82 g, 15%): lHNMR (3 〇〇MHz, CDC13) 8.97 (dd, J = 4.5, 2.1 Hz, 1H), 8.58 (dd, J = 7.8 , 2.1 Hz, 1H), 7·55 (d, J = 8·4 Hz, 2H), 7.39 (dd, J = 7.8, 4·5 Hz, 1H), 7_14 (d, J = 8.4 Hz, 2H) , 6.77 (s, 1H), 2.46 (t, J = 7.5 Hz, 2H), 1.83-1.72 (m, 2H), 1.53 (s, 9H), 1.35-1.20 (m, 2H), 0.81 (t, J = 7·5 Hz, 3H) ; MS (ES+) m/z 395.2 (M + 1). Example 57

3-(4-胺基苯基）-2-丁基吡啶并[2,3-d]嘧啶-4(3H&gt;酮之合成 按照如實例9中所述之程序，施行無關緊要之改變，使 用[4-(2-丁基-4-酮基吡啶[2,3-d]嘧啶-3(4H)·基）苯基]胺基甲酸第 三-丁酯置換5-(2-丁基-4-酮基喳唑啉·3(4Η)_基）-2,3-二氫-ΙΗ-啕 哚-1-羧酸第三-丁酯，獲得3-(4-胺基苯基）-2-丁基吡啶并[2,3-d] 嘧啶-4(3H)-酮（60%)，為無色固體：1 η NMR (300 MHz，CDC13) 5 8.95 (dd，J = 4.5, 1.8 Hz，1H)，8.57 (dd，J = 7.8, 1.8 Hz，1H)，7·38 (dd， J = 7·8, 4·8 Hz，1H)，6.97 (d，J = 8.4 Hz，2H)，6.80 (d，J = 8·4 Hz，2H)， 3.20-2.50 (寬廣 s，2H)，2.50 (t，J = 7·5 Hz，2H)，1.81-1.70 (m，2H)， 1.34-1.20 (m? 2H)5 0.82 (t? J - 7.5 Hz, 3H) ； 13 C NMR (75 MHz, CDC13) δ 163·2, 162.1，157.6, 156.1，147.5, 136.7, 128.7, 126.8, 122.0, 115.8, 35.7, 128409 -194- 200836743 31·6, 28.9, 22·3, 13·8 ; MS (ES+) m/z 295.4 (Μ + 1). 實例58 [4-(2-丁基-4-酮基喋啶_3(4Η)-基）苯基]胺基甲酸第三_丁 _之合成Synthesis of 3-(4-aminophenyl)-2-butylpyrido[2,3-d]pyrimidine-4 (3H&gt; ketone according to the procedure as described in Example 9, insignificant change, use [4-(2-Butyl-4-ketopyridine [2,3-d]pyrimidin-3(4H).yl)phenyl]carbamic acid tert-butyl ester substituted 5-(2-butyl- 4-ketooxazoline·3(4Η)-yl)-2,3-dihydro-indole-indole-1-carboxylic acid tert-butyl ester, 3-(4-aminophenyl)- 2-Butylpyrido[2,3-d]pyrimidin-4(3H)-one (60%) as colorless solid: 1 NMR (300 MHz, CDC13) 5 8.95 (dd, J = 4.5, 1.8 Hz , 1H), 8.57 (dd, J = 7.8, 1.8 Hz, 1H), 7·38 (dd, J = 7·8, 4·8 Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8·4 Hz, 2H), 3.20-2.50 (broad s, 2H), 2.50 (t, J = 7·5 Hz, 2H), 1.81-1.70 (m, 2H), 1.34-1.20 (m? 2H)5 0.82 (t? J - 7.5 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) δ 163·2, 162.1, 157.6, 156.1, 147.5, 136.7, 128.7, 126.8, 122.0, 115.8, 35.7, 128409 -194- 200836743 31·6, 28.9, 22·3, 13·8 ; MS (ES+) m/z 295.4 (Μ + 1). Example 58 [4-(2-butyl-4-keto) Acridine_3(4Η)-yl)phenyl] Acid tert-butoxy group _ _ Synthesis of

按照如實例56中所述之程序，施行無關緊要之改變，使 用3-胺基说ρ井-2-魏酸置換2-胺基終驗酸，獲得[4-(2-丁基-4-酮 基喋啶-3(4H)-基）苯基]胺基甲酸第三-丁酯（14%)，為無色固 體：1H NMR (300 MHz，CDC13) δ 8.95 (d，J = 2·1 Hz，1H)，8.81 (d，J = 2.1 Hz，lH)，7.60 (d，J = 8.7 Hz，2H)，7.18 (d，J = 8·7 Hz，2H)，6.78 (s， 1H)，2.51 (t，J = 7.5 Hz，2H)，1.84-1.70 (m，2H)，1.54 (s，9H)，1.33-1.21 (m， 2H)，0.84 (t，J = 7·5 Hz，3H) ; MS (ES+) m/z 396·2 (M + 1)· 實例59 3-(4-胺基苯基）-2-丁基喋啶_4(3H&gt;酮之合成According to the procedure as described in Example 56, an insignificant change was made, and the 2-amino group final acid was replaced with 3-amino group ρ well-2-weilic acid to obtain [4-(2-butyl-4-). Ketoacridine-3(4H)-yl)phenyl]carbamic acid tert-butyl ester (14%) as colorless solid: 1H NMR (300 MHz, CDC13) δ 8.95 (d, J = 2·1 Hz, 1H), 8.81 (d, J = 2.1 Hz, lH), 7.60 (d, J = 8.7 Hz, 2H), 7.18 (d, J = 8·7 Hz, 2H), 6.78 (s, 1H), 2.51 (t, J = 7.5 Hz, 2H), 1.84-1.70 (m, 2H), 1.54 (s, 9H), 1.33-1.21 (m, 2H), 0.84 (t, J = 7·5 Hz, 3H) MS (ES+) m/z 396·2 (M + 1) · Example 59 3-(4-Aminophenyl)-2-butylacridine_4 (3H&gt;

按照如實例9中所述之程序，施行無關緊要之改變，使 用[4-(2-丁基-4-酮基喋啶-3(4H)-基）苯基]胺基甲酸第三_丁酯置 換5-(2-丁基-4·酮基喹唑琳-3(4H)-基）-2,3-二氫-1H-吲哚-1-羧酸 第三-丁醋，獲得3-(4-胺基苯基）-2-丁基喋啶-4(3H)-酮（30%)， 為無色固體：熔點 94-96°C ; 1H NMR (300 MHz，CDC13) 5 8.92 〇, 1H)，8.78 (s，1H)，6·99 (d，J = 10.4 Hz，1H)，6.80 (d，J = 10.4 Hz, 1H)，2·53 (t，J = 7·5 Hz，2H)，1.82-1.70 (m，2H)，1.33-1.20 (m，2H)，0.83 (t，J = 7.2 Hz, 3H) ； MS (ES+) m/z 296.4 (M + 1). 128409 -195- 200836743 實例60 3-(4-胺基苯基）-2-丁基嘧吩并[3,2-d]嘧啶-4(3H&gt;酮之合成According to the procedure as described in Example 9, an insignificant change was made using [4-(2-butyl-4-ketoacridin-3(4H)-yl)phenyl]carbamic acid as the third Ester replacement of 5-(2-butyl-4. ketoquinazolin-3(4H)-yl)-2,3-dihydro-1H-indole-1-carboxylic acid tert-butyl vinegar, obtaining 3 -(4-Aminophenyl)-2-butylacridin-4(3H)-one (30%) as a colourless solid: m.p.: 94-96 ° C; 1H NMR (300 MHz, CDC13) 5 8.92 〇 , 1H), 8.78 (s, 1H), 6·99 (d, J = 10.4 Hz, 1H), 6.80 (d, J = 10.4 Hz, 1H), 2·53 (t, J = 7·5 Hz, 2H), 1.82-1.70 (m, 2H), 1.33-1.20 (m, 2H), 0.83 (t, J = 7.2 Hz, 3H); MS (ES+) m/z 296.4 (M + 1). 128409 -195 - 200836743 Example 60 Synthesis of 3-(4-aminophenyl)-2-butylsulfonio[3,2-d]pyrimidine-4 (3H&gt; ketone

按照如實例2中所述之程序，施行無關緊要之改變，使 用2-丁基-4H-噻吩并[3,2-d][l，3p号畊-4-酮置換2-丁基-4H-3，1-苯 并噚畊-4-酮，及1，4-苯二胺置換1，3-苯二胺，獲得3-(4-胺基苯 基）-2-丁基嘍吩并[3,2-d]嘧啶-4(3H)-酮（20%)，為無色固體：熔 點 180-182°C ; 1 H NMR (300 MHz，CDC13) 5 7.77 (d，J = 5.4 Hz，1H)， 7.33 (d，J = 5.4 Hz，1H)，7.03-6.96 (m，2H)，6.83-6.76 (m，2H)，4.35-3.40 (br，2H)，2.50 (t，J = 7·5 Hz，2H)，1.71-1.57 (m，2H)，1.33-1.18 (m，2H)， 0.82 (t，J = 7.5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 160.1，159.1， 156.4, 147.6, 134.3, 128.9, 127.0, 125.0, 121.5, 115·7, 35.5, 19.5, 22.4, 13.7 ; MS (ES+) m/z 300.4 (M + 1). 實例61 3-(4-胺基苯基）_2-丁基噻吩并[2,3-d]嘧啶-4(3H)-酮之合成According to the procedure as described in Example 2, irrelevant changes were made using 2-butyl-4H-thieno[3,2-d][l,3p cultiv-4-one to replace 2-butyl-4H -3,1-Benzoindole-4-one, and 1,4-phenylenediamine are substituted for 1,3-phenylenediamine to obtain 3-(4-aminophenyl)-2-butyl porphin [3,2-d]pyrimidin-4(3H)-one (20%) as colorless solid: m.p. 180-182°C; 1H NMR (300 MHz, CDC13) 5 7.77 (d,J = 5.4 Hz, 1H), 7.33 (d, J = 5.4 Hz, 1H), 7.03-6.96 (m, 2H), 6.83-6.76 (m, 2H), 4.35-3.40 (br, 2H), 2.50 (t, J = 7· 5 Hz, 2H), 1.71-1.57 (m, 2H), 1.33-1.18 (m, 2H), 0.82 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 160.1, 159.1, 156.4 , 147.6, 134.3, 128.9, 127.0, 125.0, 121.5, 115·7, 35.5, 19.5, 22.4, 13.7; MS (ES+) m/z 300.4 (M + 1). Example 61 3-(4-Aminophenyl) Synthesis of 2-2-butylthieno[2,3-d]pyrimidin-4(3H)-one

按知如κ例2中所述之程序，施行無關緊要之改變，使 用2-丁基-4Η-噻吩并[2,3_d][l，3]呤畊-4-酮置換2-丁基-4Η-3，1-苯 并哼畊-4-酮，及ΐ，4-苯二胺置換丨义苯二胺，獲得3·(4_胺基苯 基）-2-丁基隹吩并[2&gt;d]嘧啶-4(3H)-g同（7%)，為無色固體：熔 點 185-187°C ; NMR (300 MHz，CDC13) 5 7.44 (d，J = 5.7 Hz，1H)， 7.16 (d，J = 5.7 Hz，1H)，7.00-6.91 (m，2H)，6.82-6.74 (m，2H)，4.20-3.60 128409 -196- 200836743 (br，2H)，2·46 (t，J = 7·5 Hz，2H)，1.70-1.57 (m，2H)，1.32-1.18 (m，2H)， 0.82 (t，J = 7·5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 3 163.9, 159.5, 159.0, 147.4, 128.9 127.3, 122.7，122.5，122.4，115.9, 35.6, 29.3, 22.4, 13.8 ； MS (ES+) m/z 300.4 (M + 1). 實例62 3-(4-胺基苯基）-2-丁基-6_氣基喳唑啉-4(3H)-酮之合成Inconsistent changes were made according to the procedure described in Example 2, using 2-butyl-4Η-thieno[2,3_d][l,3] 呤-4-ketone to replace 2-butyl- 4Η-3,1-benzoxanthene-4-one, and hydrazine, 4-phenylenediamine substituted 丨-phenylenediamine to obtain 3·(4-aminophenyl)-2-butylindole [ 2&gt;d]pyrimidin-4(3H)-g identical (7%) as colorless solid: mp 185-187 ° C; NMR (300 MHz, CDC13) 5 7.44 (d, J = 5.7 Hz, 1H), 7.16 (d, J = 5.7 Hz, 1H), 7.00-6.91 (m, 2H), 6.82-6.74 (m, 2H), 4.20-3.60 128409 -196- 200836743 (br, 2H), 2·46 (t, J = 7·5 Hz, 2H), 1.70-1.57 (m, 2H), 1.32-1.18 (m, 2H), 0.82 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 3 163.9, 159.5, 159.0, 147.4, 128.9 127.3, 122.7, 122.5, 122.4, 115.9, 35.6, 29.3, 22.4, 13.8; MS (ES+) m/z 300.4 (M + 1). Example 62 3-(4-Amino Synthesis of phenyl)-2-butyl-6-glyoxazoline-4(3H)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用2-胺基-5-氣-苯甲酸置換2-胺基菸鹼酸，及丨，4-苯二胺置換 4-胺基苯基胺基甲酸第三_丁酯，獲得3-(4-胺基苯基丁基 -6-氯基喹唾啉-4(3H)-酮（35%)，為無色固體：1H NMR (300 MHz， CDC13) δ 8.21 (dd? J = 2.1? 0.6 Hz, 1H), 7.71-7.60 (m? 1H), 7.01-6.93 (m5 2H)，6.82-6.74 (m，2H)，4.20-3.60 (br，2H)，2.46 (t，J 二 7.5 Hz，2H)， 1.69-1.57 (m? 2H)5 1.32-1.17 (m, 2H)3 0.82 (t? J = 7.5 Hz? 3H) ； 13 C NMR (75 MHz，CDC13) 6 162.1，158.6, 147.4, 146.2, 134.8, 132.1，129.0, 128.8, 127.3, 126.4, 121.9, 115·9, 35/7, 29.3, 22.5, 13.9 ; MS (ES+) m/z 328.1 (M + 1), 330.1 (M + 1). 3-(4-胺基苯基）_2·丁基-7-氣基喳唑啉-4(3H&gt;酮之合成 實例63According to the procedure as described in Example 56, irrelevant changes were made, 2-aminopentinic acid was replaced with 2-amino-5-gas-benzoic acid, and 4-amino group was replaced by hydrazine and 4-phenylenediamine. Phenylaminocarbamic acid tert-butyl ester gave 3-(4-aminophenylbutyl-6-chloroquinoxalin-4(3H)-one (35%) as a colorless solid: 1H NMR ( 300 MHz, CDC13) δ 8.21 (dd? J = 2.1? 0.6 Hz, 1H), 7.71-7.60 (m? 1H), 7.01-6.93 (m5 2H), 6.82-6.74 (m, 2H), 4.20-3.60 ( Br,2H),2.46 (t,J 2 7.5 Hz, 2H), 1.69-1.57 (m? 2H)5 1.32-1.17 (m, 2H)3 0.82 (t? J = 7.5 Hz? 3H) ; 13 C NMR (75 MHz, CDC13) 6 162.1, 158.6, 147.4, 146.2, 134.8, 132.1, 129.0, 128.8, 127.3, 126.4, 121.9, 115·9, 35/7, 29.3, 22.5, 13.9; MS (ES+) m/z 328.1 (M + 1), 330.1 (M + 1). 3-(4-Aminophenyl)_2-butyl-7-yloxaxazoline-4 (3H&gt; Ketone Synthesis Example 63

128409 -197- 200836743 按照如實例56中所述之程序，施行無關緊要之改變，使 用2-胺基-4-氯-苯甲酸置換2-胺基菸鹼酸，及丨，4-苯二胺置換 4-胺基苯基胺基甲酸第三-丁酯，獲得3-…胺基苯基）士 丁基 -7-氯基七坐琳_4(311&gt;酮（35%)，為無色固體：丨H麵汉（3〇〇 mHz， CDC13) 5 8.17 (d，J = 8·7 Hz，1H)，7.69 (s，1H)，7·38 (dd，J = 8.7, 1.8 Hz， 1H)，7.01-6.90 (m，2H)，6.83-6.74 (m，2H)，4.20-3.60 (br，2H)，2.46 (t，J = 7.8 Hz，2H)，1·72-1·57 (m，2H)，1·34·1·17 (m，2H)，0.83 (t，J = 7.5 Hz， 3H) ; 13C NMR (75 MHz，CDC13) 5 162.5, 159.7, 148.7, 147.4, 140.6, 129.0, 128.7, 127.4, 127.1，126.7, 119.4, 115.9, 35.7, 29.3, 22.5, 13.9 ; MS (ES+) m/z 328.1 (M + 1)，330.1 (M + 1). 實例64 3-(4-胺基苯基）-2-丁基吡啶并[3,4-d]嘧啶-4(3H)-酮之合成128409-197-200836743 According to the procedure as described in Example 56, irrelevant changes were made using 2-amino-4-chloro-benzoic acid to replace 2-aminonicotinic acid, and hydrazine, 4-phenylenediamine Displacement of 3-aminophenylaminocarbamic acid tert-butyl ester to give 3-(aminophenyl)-tert-butyl-7-chloro-succinyl- 4 (311) ketone (35%) as a colorless solid :丨H面汉(3〇〇mHz, CDC13) 5 8.17 (d, J = 8·7 Hz, 1H), 7.69 (s, 1H), 7·38 (dd, J = 8.7, 1.8 Hz, 1H) , 7.01-6.90 (m, 2H), 6.83-6.74 (m, 2H), 4.20-3.60 (br, 2H), 2.46 (t, J = 7.8 Hz, 2H), 1.72-1·57 (m, 2H),1·34·1·17 (m, 2H), 0.83 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.5, 159.7, 148.7, 147.4, 140.6, 129.0, 128.7 , 127.4, 127.1, 126.7, 119.4, 115.9, 35.7, 29.3, 22.5, 13.9; MS (ES+) m/z 328.1 (M + 1), 330.1 (M + 1). Example 64 3-(4-Aminobenzene Synthesis of 2-butylpyrido[3,4-d]pyrimidin-4(3H)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用3-胺基-吡啶冰羧酸置換2-胺基菸鹼酸，及1，4-苯二胺置換 4-胺基苯基胺基甲酸第三-丁酯，獲得3_…胺基苯基）_2_丁基 吡啶并[3,4-d]嘧啶-4(3H)-酮（8%)，為無色固體：4 NMR (300 MHz，CDC13) 6 9.14 (s，1H)，8.65 (d，J = 4·0 Hz，1H)，8.04 (d，J = 5·1 Hz， 1H)，7.01-6.95 (m，2H)，6.84-6.77 (m，2H)，2.49 (t，J = 7·5 Hz，2H)， 1.76-1.62 (m，2H)，1.37-1.21 (m，2H)，0.84 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) δ 161.9, 160.5, 151.0, 147.6, 146.0, 142.4, 128.8, 126.9, 125.8, 119.0, 115.9, 35.7, 29.2, 22.4, 13.9 ; MS (ES+) m/z 295.2 (M + 1). 128409 -198- 200836743 實例65 2-丁基-3_(4-氟苯基 &gt;奎唑啉_4(3H)_酮之合成According to the procedure as described in Example 56, irrelevant changes were made, replacing 2-aminonicotinic acid with 3-amino-pyridine carboxylic acid, and 4-aminophenyl replacing 1,4-phenylenediamine. Third-butyl carbamic acid ester, 3 -...aminophenyl) 2 -butylpyrido[3,4-d]pyrimidin-4(3H)-one (8%) as a colorless solid: 4 NMR ( 300 MHz, CDC13) 6 9.14 (s, 1H), 8.65 (d, J = 4·0 Hz, 1H), 8.04 (d, J = 5·1 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.77 (m, 2H), 2.49 (t, J = 7·5 Hz, 2H), 1.76-1.62 (m, 2H), 1.37-1.21 (m, 2H), 0.84 (t, J = 7.5) Hz,3H) ; 13 C NMR (75 MHz, CDC13) δ 161.9, 160.5, 151.0, 147.6, 146.0, 142.4, 128.8, 126.9, 125.8, 119.0, 115.9, 35.7, 29.2, 22.4, 13.9 ; MS (ES+) m /z 295.2 (M + 1). 128409 -198- 200836743 Example 65 Synthesis of 2-butyl-3_(4-fluorophenyl) quinazoline-4(3H)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4-氟苯胺置換4-胺基 苯基胺基甲酸第三-丁酯，獲得孓丁基各(4_氟苯基）峻唑啉 4(3H)_酮（26%)，為無色固體：iH NMR (3〇〇 MHz，CDCl3)占According to the procedure as described in Example 56, an insignificant change was made, replacing the 2-aminonicotinic acid with o-aminobenzoic acid, and the 4-aminophenylaminocarboxylic acid third-butyl with 4-fluoroaniline. The ester was obtained as a butyl butyl group (4-fluorophenyl) thiazoline 4 (3H) ketone (26%) as a colorless solid: iH NMR (3 〇〇 MHz, CDCl3)

8.27-8.21 (m，1H)，7.78-7.66 (m，2H)，7.48-7.41 (m，1H)，7.24 (s，2H)，7·22 (s，2H)，2.40 (t，J = 7·5 Hz，2H)，1.70-1.58 (m，2H)，1.32-1.17 (m5 2H)，0.80 (t，J = 7·5 Hz，3H) ; 13C NMR (75 MHZ，CDC13) 5 164.5, 162,7, 161.2, 157.1，147.6, 134.7, 133.4 (d，J = 15 Hz)，130.3 (d，J = 36 Hz)，127.2 (d，J8.27-8.21 (m,1H), 7.78-7.66 (m,2H), 7.48-7.41 (m,1H), 7.24 (s,2H),7·22 (s,2H), 2.40 (t,J = 7 · 5 Hz, 2H), 1.70-1.58 (m, 2H), 1.32-1.17 (m5 2H), 0.80 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHZ, CDC13) 5 164.5, 162 , 7, 161.2, 157.1, 147.6, 134.7, 133.4 (d, J = 15 Hz), 130.3 (d, J = 36 Hz), 127.2 (d, J

=24 Hz)，126.8, 120.7, 117.0 (d5 J = 93 Hz)，35 7, 29 3, 22 5, 13 8 ; MS (ES+) m/z 297.2 (M + 1). 實例66=24 Hz), 126.8, 120.7, 117.0 (d5 J = 93 Hz), 35 7, 29 3, 22 5, 13 8 ; MS (ES+) m/z 297.2 (M + 1). Example 66

2-丁基-7-硝基苯基喳唑啉_4(3H)__之合成 o2n 按 照如實例56中所述之程序 - ^ 施仃無關緊要之改變，使 用4-硝基-鄰胺基苯甲酸置換2 且供基菸鹼酸，及苯胺置換4_ 胺基苯基胺基甲酸第三-丁酷 知’獲得2-丁基-7-硝基！苯基喳 唑啉-4(3H)·酮（50%)，為無色固體：溶 MHz，CDC13) 5 8.56 (d，J = 2·1 Ηζ)，8·42 點 104-105°C ; hNMRpOO (d，J = 8.7 Hz)，8.21 (dd，J = 8.7, 2·1 Hz，1H)，7.64-7.52 (m， 3HX 7.26 (dd5 J = 7.55 1.5 Hz5 2H)5 2.44 (t? 128409 ' 199- 200836743 J = 7·5 Hz，2H), 1.76-1.64 (m，2H)，1.35-1.21 (m，2H)，0·83 (t，J = 7.5 Hz， 3H) ; 13C NMR (75 MHz，CDC13) δ 161.4, 159.8, 151.8, 148.2, 136.7, 130.2, 129.8, 129.0, 128.2, 125.0, 127.9, 120.2, 35.7, 28.9, 22.3, 13.8 ; MS (ES+) m/z 324.2 (M + 1). 實例67 2-丁基-6-硝基-3-苯基喹唑啉-4(3H&gt;_之合成Synthesis of 2-butyl-7-nitrophenyloxazoline-4(3H)__ o2n Following the procedure as described in Example 56 - ^ Insignificant change, using 4-nitro-o-amine Substituting benzoic acid for 2 and supplying nicotinic acid, and aniline for 4_aminophenylaminocarbamic acid, the third - butyl know 'to obtain 2-butyl-7-nitro! Phenyloxazoline-4(3H)·one (50%) as a colorless solid: mp. mp., cd, mp, mp, mp, mp, mp, mp. (d, J = 8.7 Hz), 8.21 (dd, J = 8.7, 2·1 Hz, 1H), 7.64 - 7.52 (m, 3HX 7.26 (dd5 J = 7.55 1.5 Hz5 2H) 5 2.44 (t? 128409 ' 199 - 200836743 J = 7·5 Hz, 2H), 1.76-1.64 (m, 2H), 1.35-1.21 (m, 2H), 0·83 (t, J = 7.5 Hz, 3H) ; 13C NMR (75 MHz, CDC13) δ 161.4, 159.8, 151.8, 148.2, 136.7, 130.2, 129.8, 129.0, 128.2, 125.0, 127.9, 120.2, 35.7, 28.9, 22.3, 13.8 ; MS (ES+) m/z 324.2 (M + 1). Synthesis of 67 2-butyl-6-nitro-3-phenylquinazoline-4 (3H&gt;_

按照如實例56中所述之程序，施行無關緊要之改變，使 用5-硝基-鄰胺基苯甲酸置換2-胺基終驗酸，及苯胺置換4-胺基苯基胺基甲酸第三-丁酯，獲得2_丁基硝基-3-苯基喳 唑琳-4(3H)-酮（24%)，為無色固體：炼點 i45-146°C ; 1H NMR (300 MHz，CDC13) 5 9.12 (d，J = 2.7 Hz)，（dd，J = 9.0, 2·7 Ηζ，1Η)，7·82 (d，J =9.0 Hz)，7.64-7.52 (m，3H)，7.28-7.22 (m，2H)，2.46 (t，J = 7.5 Hz，2H)， 1.76-1.64 (m，2H)，1.35-1.20 (m，2H)，0.82 (t5 J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 6 161.5, 161.2, 151.8, 145.6, 136.6, 130.2, 129.9, 128.8, 128.6, 128.2, 123.8, 121.0, 35.9, 29.1，22.4, 13·8 ; MS (ES+) m/z 324.2 (M + 1). 實例68 2-丁基-3_(4-氣苯基 &gt;奎唑啉_4(3H)_酮之合成According to the procedure as described in Example 56, an insignificant change was made, replacing the 2-amino-based final acid with 5-nitro-o-aminobenzoic acid, and the fourth 4-aminophenylaminocarboxylic acid with aniline. - butyl ester, 2 - butyl nitro-3-phenyl oxazolidine - 4 (3H)-one (24%) was obtained as a colorless solid: ss. i45-146 ° C; 1H NMR (300 MHz, CDC13 5 9.12 (d, J = 2.7 Hz), (dd, J = 9.0, 2·7 Ηζ, 1 Η), 7·82 (d, J = 9.0 Hz), 7.64 - 7.52 (m, 3H), 7.28- 7.22 (m, 2H), 2.46 (t, J = 7.5 Hz, 2H), 1.76-1.64 (m, 2H), 1.35-1.20 (m, 2H), 0.82 (t5 J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 6 161.5, 161.2, 151.8, 145.6, 136.6, 130.2, 129.9, 128.8, 128.6, 128.2, 123.8, 121.0, 35.9, 29.1, 22.4, 13·8 ; MS (ES+) m/ z 324.2 (M + 1). Example 68 Synthesis of 2-butyl-3_(4-phenylphenyl) quinazoline-4(3H)-one

及4-氯苯胺置換4-胺基 按&quot;、、士 μ例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲g曼置換2_胺基於驗酸 128409 -200- 200836743 笨基胺基甲酸第三-丁酯，獲得2_丁基_3-(4-氯苯基唑啉 _4(3H)-嗣（39%)，為無色固體··熔點 9〇-92〇c ; iHNMR(3〇〇MHz， CDC13) δ 8.28-8.23 (m? 1H)3 7.82-7.68 (m5 2H)3 7.58-7.43 (m5 3H)? 7.24-7.17 (m，2H)，2.42 (t，J = 7·5 Hz，2H)，1.73-1.61 (m5 2H)，1.34-1.20 (m，2H)，0.83 (t，J = 7.5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 162.5, 156.7, 147.6, 136.0, 135.4, 134.8, 130.2, 129.9, 127.2, 127.1，126.8, 120.7, 35.7, 29.3, 22.4，13.8 ; MS (ES+) m/z 313.1 (M + 1)，315·1 (M + 1)· 實例69 7-胺基-2-丁基-3-苯基喹唑啉-4(3H)-酮之合成And 4-chloroaniline replacement of 4-amino group according to the procedure described in &quot;,, μ, example 56, insignificant changes, using o-amino benzoyl gman replacement 2_ amine based on acid test 128409-200- 200836743 Tert-butyl ester of phenylaminocarbamic acid, which gives 2-butyl-3-(4-chlorophenyloxazoline-4(3H)-indole (39%) as a colorless solid. 〇c ; iHNMR(3〇〇MHz, CDC13) δ 8.28-8.23 (m? 1H)3 7.82-7.68 (m5 2H)3 7.58-7.43 (m5 3H)? 7.24-7.17 (m,2H), 2.42 (t , J = 7·5 Hz, 2H), 1.73-1.61 (m5 2H), 1.34-1.20 (m, 2H), 0.83 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.5, 156.7, 147.6, 136.0, 135.4, 134.8, 130.2, 129.9, 127.2, 127.1, 126.8, 120.7, 35.7, 29.3, 22.4, 13.8; MS (ES+) m/z 313.1 (M + 1), 315·1 ( M + 1)·Example 69 Synthesis of 7-Amino-2-butyl-3-phenylquinazoline-4(3H)-one

使2-丁基-7-硝基_3-苯基喹唑啉-4(3H)-酮（0.500克，1.55毫莫 耳）在甲醇中，於1大氣壓下，使用10〇/〇 pd/c (〇 〇6〇克）作為觸 媒，在環境温度下氫化十六小時。經過石夕藻土過濾混合物， 並使濾液蒸發至乾涸。使殘留物接受管柱層析（在己烷中之 50%醋酸乙酯），獲得7_胺基·2_丁基各苯基喳唑啉_4(3H)_酮 (0_240 克，53%)，為無色固體：熔點 129·ΐ3Γ〇 ; 1 H NMR (300 MHz， CDCI3) 5 8.04 (d5 J = 8.7 Hz5 lH), 7.59-7.44 (m5 3H)? 7.25-7.19 (m? 2H), 6.85 (s，1H)，7.75 (dd，J = 8.7, 2·1 Hz，1H)，4.25 (s，2H)，2.40 (t，J = 7.5 Hz，2H)，1.69-1.57 (m，2H)，1.29-U5 (m，2H)，0·77 (t，J = 7·5 Hz，3H); 13C NMR (75 MHz，CDC13) 5 162.1，157.6, 152.5, 149.5, 137.6, 129.7, 129.0, 128.8, 128_6, 115.2, 111.7, 108.5, 35.5, 29.4, 22.3, 13.6 ; MS (ES+) m/z 294.2 (M + 1)· 128409 -201 - 200836743 實例70 3-(2,3-一 .基丙基）_2_甲基喳唑淋_4(3H)-_之合成2-butyl-7-nitro-3-phenyl quinazolin-4(3H)-one (0.500 g, 1.55 mmol) in methanol at 1 atm, using 10 〇/〇pd/ c (〇〇6 g) was used as a catalyst and hydrogenated at ambient temperature for 16 hours. The mixture was filtered through celite, and the filtrate was evaporated to dryness. The residue was subjected to column chromatography (50% ethyl acetate in hexane) to afford 7-amino-2-y-butyl phenyl oxazoline _ 4 (3H) ketone (0-240 g, 53% ), as a colorless solid: melting point 129·ΐ3Γ〇; 1 H NMR (300 MHz, CDCI3) 5 8.04 (d5 J = 8.7 Hz5 lH), 7.59-7.44 (m5 3H)? 7.25-7.19 (m? 2H), 6.85 (s, 1H), 7.75 (dd, J = 8.7, 2·1 Hz, 1H), 4.25 (s, 2H), 2.40 (t, J = 7.5 Hz, 2H), 1.69-1.57 (m, 2H), 1.29-U5 (m, 2H), 0·77 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.1, 157.6, 152.5, 149.5, 137.6, 129.7, 129.0, 128.8, 128_6, 115.2, 111.7, 108.5, 35.5, 29.4, 22.3, 13.6; MS (ES+) m/z 294.2 (M + 1)· 128409 -201 - 200836743 Example 70 3-(2,3-monopropyl) Synthesis of _2_methylcarbazole _4(3H)-_

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及2,3-二羥基-1-胺基-丙 烧置換4-胺基苯基胺基甲酸第三_ 丁酯，且醋酸酐置換戊酸 酐’獲付3-(2,3_一 .基丙基）-2-甲基p奎嗅琳-4(3H)-酮（30%)，為 無色固體··熔點 126-128°C ; hNMR (300 MHz，CDC13) 5 8.19 (dd， J 二 7.8, 1.5 Hz，1H)，7.78-7.70 (m，1H)，7.61 (d，J = 7.5 Hz), 7.48-7.42 (m， 1H)，4.38 (dd，J = 13.8, 4.8 Hz，1H)，4.13 (dd，J = 13.8, 6·6 Hz，1H)， 4.12-4.00 (br，1H)，3.78-3.52 (m，2H)，3.40-3.26 (m，1H)，3.09-2.84 (m， 1H), 2.73 (s? 3H) ； !3C NMR (75 MHz5 CDC13) 5 163.8, 158.3, 148.2, 135.7, 127.6, 127.4, 127.0, 70.6, 65.4, 48.4, 23.7; MS (ES+) m/z 234.2 (m). 實例71 6-胺基-2-丁基-3_苯基p奎峻p林-4(3H)·酮之合成According to the procedure as described in Example 56, irrelevant changes were made, replacing the 2-aminonicotinic acid with o-aminobenzoic acid and the 4-amine with 2,3-dihydroxy-1-amino-propanol. Benzylaminocarbamic acid tert-butyl ester, and acetic anhydride replacing valeric anhydride 'paid 3-(2,3-monopropyl)-2-methyl p-quinolyl-4(3H)-one (30%), as a colorless solid, melting point 126-128 ° C; hNMR (300 MHz, CDC13) 5 8.19 (dd, J 2 7.8, 1.5 Hz, 1H), 7.78-7.70 (m, 1H), 7.61 ( d, J = 7.5 Hz), 7.48-7.42 (m, 1H), 4.38 (dd, J = 13.8, 4.8 Hz, 1H), 4.13 (dd, J = 13.8, 6·6 Hz, 1H), 4.12-4.00 (br,1H), 3.78-3.52 (m,2H), 3.40-3.26 (m,1H), 3.09-2.84 (m, 1H), 2.73 (s? 3H) ; !3C NMR (75 MHz5 CDC13) 5 163.8 , 158.3, 148.2, 135.7, 127.6, 127.4, 127.0, 70.6, 65.4, 48.4, 23.7; MS (ES+) m/z 234.2 (m). Example 71 6-Amino-2-butyl-3_phenyl p Synthesis of Kui Jun Pulin-4(3H)·ketone

按照如實例69中所述之程序，施行無關緊要之改變，使 用2-丁基-6-硝基-3-苯基峡唑琳-4(3H)-酮置換2-丁基-7-硝基-3-苯基喹唑啉·4(3Η&gt;_，獲得6-胺基-2-丁基-3-苯基喳唑啉-4(3H)-酮（33%)，為無色固體：iHNMR(300 MHz，CDC13) 5 7.61-7.41 (m， 5H)，7.30-7.19 (m，2H)，7·11 (dd，J = 8.7, 2·7 Hz, 1H)，2.39 (t，J = 7.5 Hz， 2H)，1.62 (五重峰，j ：= 7.5 Hz，2H)，123435 (m，2H)，〇 77 (t，】=7 5 128409 -202- 200836743Inconsistent changes were made according to the procedure described in Example 69, using 2-butyl-6-nitro-3-phenyloxazolin-4(3H)-one to replace 2-butyl-7-nitrate Benzyl-3-phenylquinazoline·4 (3Η&gt;_, 6-amino-2-butyl-3-phenyloxazoline-4(3H)-one (33%) as a colorless solid: iHNMR (300 MHz, CDC13) 5 7.61-7.41 (m, 5H), 7.30-7.19 (m, 2H), 7·11 (dd, J = 8.7, 2·7 Hz, 1H), 2.39 (t, J = 7.5 Hz, 2H), 1.62 (five peaks, j:= 7.5 Hz, 2H), 123435 (m, 2H), 〇77 (t,] = 7 5 128409 -202- 200836743

Hz，3H); 13C NMR (75 MHz, CDC13) 5 162.4, 153.5, 145.4, 140.3, 137.7, 129.7, 129.1，128.4, 128.1，123.3, 121.6, 109.2, 352, 29.4, 22.3, 21.1，14.2, 13.6 ； MS (ES+) m/z 294.2 (M + 1). 實例72 [3-(2•丁基-4-酮基喹唑啉-3(4H)-基）丙基]胺基甲酸第三-丁酯之 合成Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.4, 153.5, 145.4, 140.3, 137.7, 129.7, 129.1, 128.4, 128.1, 123.3, 121.6, 109.2, 352, 29.4, 22.3, 21.1, 14.2, 13.6; MS (ES+) m/z 294.2 (M + 1). Example 72 [3-(2 butyl-4-ketoquinazolin-3(4H)-yl)propyl] carbamic acid Ester synthesis

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及3-胺基丙基胺基甲酸 第三-丁醋置換4-胺基苯基胺基曱酸第三-丁醋，獲得[3-(2-丁 基-4-酮基喳唑啉-3(4H)-基）丙基]胺基曱酸第三-丁酯（34%)，為 無色固體：iH NMR (300 MHz，CDC13) δ 8.24 (dd，J = 8.1，1.5 Hz， 1H)，7.77-7.59 (m，2H)，7·44 (td，J = 8.1，1·2 Hz，1H)，5.29-5.15 (br，1H)， 4.19 (t，J = 6·9 Hz，2H)，3.19 (td，J = 6.3, 6.3 Hz，2H)，2·82 (t，J = 7.5 Hz， 2H)，1.96-1.77 (m，4H)，1.58-1.39 (m，11H)，1.0 (t，J = 7·5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.9, 157.0, 156.2, 147.4, 134.4, 127.0, 126.8, 126.5, 120.3, 79.4, 41.0, 37.7, 34.9, 29.9, 29.8, 28.5, 22.7, 14.0 ; MS (ES+) m/z 360.2 (M + 1)? 260.2 (M - Boc). 實例73 [2-(2-丁基-4-酮基喹唑琳-3(4H)-基）乙基]胺基甲酸第三_丁酯之 合成According to the procedure as described in Example 56, an insignificant change was made, replacing the 2-aminonicotinic acid with o-aminobenzoic acid, and the 4-amine carboxylic acid replacing the 4-amine with 3-aminopropylaminocarbamic acid. Phenylamino decanoic acid tert-butyl vinegar, obtaining [3-(2-butyl-4-ketooxazoline-3(4H)-yl)propyl]amino decanoic acid tert-butyl ester (34%) as colorless solid: iH NMR (300 MHz, CDC13) δ 8.24 (dd, J = 8.1, 1.5 Hz, 1H), 7.77-7.59 (m, 2H), 7.44 (td, J = 8.1 ,1·2 Hz,1H),5.29-5.15 (br,1H), 4.19 (t,J = 6·9 Hz, 2H), 3.19 (td, J = 6.3, 6.3 Hz, 2H), 2·82 ( t, J = 7.5 Hz, 2H), 1.96-1.77 (m, 4H), 1.58-1.39 (m, 11H), 1.0 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.9, 157.0, 156.2, 147.4, 134.4, 127.0, 126.8, 126.5, 120.3, 79.4, 41.0, 37.7, 34.9, 29.9, 29.8, 28.5, 22.7, 14.0 ; MS (ES+) m/z 360.2 (M + 1) 260.2 (M - Boc). Example 73 Synthesis of [2-(2-butyl-4-ketoquinazolin-3(4H)-yl)ethyl]aminocarbamic acid tert-butyl ester

128409 -203 - 200836743 按妝如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基笨甲酸置換2·胺基菸鹼酸，及2-胺基乙基胺基甲酸 第一-丁 §曰置換4_胺基苯基胺基甲酸第三-丁醋，獲得[2-(2-丁 基-4-綱基峻唾琳基）乙基]胺基甲酸第三_丁酯⑽，為 無色固體·熔點 132]34〇c ; i H ⑼〇 MHz，CDC13 ) 5 8 23 (dd， J 8·1，1·2 Hz，1H)，7.77-7.59 (m，2H)，7.43 (td，J = 8.1，1·2 Hz，1H)， 4.97-4.81 (br，1H)，4.25 (t，J = 6.3 Hz，2H)，3.48 (td，J = 6.0, 6·0 Hz，2H)， 2.90 (t，J - 7.5 Hz，2H)，1.80 (五重峰，j = 7·5 Hz，2H)，！ 58] 42 ㈣ 2H)，1.40 (s，9H)，〇·99 (t，J = 7.5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 162.7, 157.6, 156.2, 147.3, 134.3, 126.9, 126.6, 126.4, 120.2, 43.4, 39.3, 34.9, 29.8, 28.3, 22.5, 13.9 ; MS (ES+) m/z 346.2 (M + 1). 實例74 3-(2-胺基乙基）_2-丁基p奎唑琳_4(3H)_酮二鹽酸鹽之合成128409 -203 - 200836743 According to the procedure described in Example 56, irrelevant changes were made using o-amino benzoic acid to replace 2 -aminonicotinic acid, and 2-aminoethylaminocarboxylic acid first - Ding 曰 曰 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 , is a colorless solid, melting point 132] 34〇c; i H (9) 〇 MHz, CDC13) 5 8 23 (dd, J 8·1,1·2 Hz, 1H), 7.77-7.59 (m, 2H), 7.43 ( Td,J = 8.1,1·2 Hz,1H), 4.97-4.81 (br,1H), 4.25 (t,J = 6.3 Hz, 2H), 3.48 (td, J = 6.0, 6·0 Hz, 2H) , 2.90 (t, J - 7.5 Hz, 2H), 1.80 (five peaks, j = 7·5 Hz, 2H),! 58] 42 (4) 2H), 1.40 (s, 9H), 〇·99 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.7, 157.6, 156.2, 147.3, 134.3, 126.9, 126.6, 126.4, 120.2, 43.4, 39.3, 34.9, 29.8, 28.3, 22.5, 13.9; MS (ES+) m/z 346.2 (M + 1). Example 74 3-(2-Aminoethyl)_2-butyl Synthesis of p-quinazoline _4(3H)-ketone dihydrochloride

八^NH2 2 HCI 於[2-(2-丁基-4-酮基喳唑啉-3(4H)-基）乙基]胺基甲酸第三-丁 酯（0.300克，0.868毫莫耳）在甲醇（3·〇毫升）中之溶液内，添 加二氧陸圜中之4·0Μ HC1溶液（4毫升）。將混合物於環境溫 度下攪拌三十分鐘，並在真空中蒸發至乾涸。以無水醚（5() 晕升）研製殘留物’而付3-(2-胺基乙基）丁基7奎^坐琳_4(3Η)_ 酉同二鹽酸鹽（0.235克’ 85%)，為無色固體·· 1 η NMR (300 ΜΗζ， CD3〇D) ^8.36(d，J = 7.8Hz，lH)，8.05(td，J = 7.8,0.9Hz，lH)，7.87-7.72 (m，2H)，4.59 (t，J = 6·0 Hz，2H)，3.44 (t，J = 6·0 Hz，2H)，3.30-3.17 (m，2H)，1.96-1.82 (m，2H)，1.72-1.57 (m，2H)，1.06 (t，J = 7·5 Hz，3H); 128409 -204- 200836743 13C NMR (75 MHz, CD3〇D) 5 165.8, 161.1，138.4, 138.1，130.7, 129·0, 120.3, 120.0, 43.8, 39.0, 34.0, 30.9, 23.7, 14.0 ; MS (ES+) m/z 246·2 (M + 1)· 實例75 3-(3-胺基丙基&gt;2-丁基喹唑啉-4(3H)-酮二鹽酸鹽之合成Octa NH2 2 HCI to [2-(2-butyl-4-ketooxazoline-3(4H)-yl)ethyl]carbamic acid tert-butyl ester (0.300 g, 0.868 mmol) A solution of 4·0 Μ HC1 (4 ml) in dioxane was added to a solution of methanol (3·ml). The mixture was stirred at ambient temperature for thirty minutes and evaporated to dryness in vacuo. The residue was developed with anhydrous ether (5() swell) and 3-(2-aminoethyl)butyl 7 quinone^ sitting _4(3Η)_ 酉同二盐盐(0.235克' 85 %), as a colorless solid·· 1 η NMR (300 ΜΗζ, CD3〇D) ^8.36 (d, J = 7.8 Hz, lH), 8.05 (td, J = 7.8, 0.9 Hz, lH), 7.87-7.72 ( m, 2H), 4.59 (t, J = 6·0 Hz, 2H), 3.44 (t, J = 6·0 Hz, 2H), 3.30-3.17 (m, 2H), 1.96-1.82 (m, 2H) , 1.72-1.57 (m, 2H), 1.06 (t, J = 7·5 Hz, 3H); 128409 -204- 200836743 13C NMR (75 MHz, CD3〇D) 5 165.8, 161.1, 138.4, 138.1, 130.7, 129·0, 120.3, 120.0, 43.8, 39.0, 34.0, 30.9, 23.7, 14.0; MS (ES+) m/z 246·2 (M + 1)· Example 75 3-(3-Aminopropyl)&gt; Synthesis of butylquinazoline-4(3H)-one dihydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用[3-(2-丁基-4-W基喳唑啉-3(4H)-基）丙基]胺基甲酸第三-丁酯 置換[2-(2-丁基-4-酮基峻。坐琳_3(4H)_基）乙基]胺基甲酸第三-丁 醋’獲得3-(3-胺基丙基）_2•丁基喳唑啉·4(3Η)-酮二鹽酸鹽 (55%)，為無色固體：1 H NMR (3〇〇 MHz，CD3 〇D)占 8 % ㈣ j = 8.1，0·9 Hz，1H)，8.05 (td，J = 7.5, 0·9 Hz，1H)，7.87-7.72 (m，2H), 4.37 (t， J = 7·5 Hz，2H)，3.27-3.10 (m，4H)，2 20 (五重峰，j = 7 5 Hz，2H)，According to the procedure as described in Example 74, an irrelevant change was carried out using [3-(2-butyl-4-W-oxazoline-3(4H)-yl)propyl]aminocarboxylic acid third- Butyl ester replacement [2-(2-butyl-4-keto-jun. sitin_3(4H)-yl)ethyl]aminocarbamic acid tert-butyl vinegar' to obtain 3-(3-aminopropyl) _2• butyl oxazoline·4(3Η)-one dihydrochloride (55%) as a colorless solid: 1 H NMR (3 〇〇 MHz, CD3 〇D) 8% (4) j = 8.1,0 · 9 Hz, 1H), 8.05 (td, J = 7.5, 0·9 Hz, 1H), 7.87-7.72 (m, 2H), 4.37 (t, J = 7·5 Hz, 2H), 3.27-3.10 ( m, 4H), 2 20 (five peaks, j = 7 5 Hz, 2H),

1.97-1.84 (m，2H)，1.72-1.57 (m，2H)，1.07 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CD3〇D) 5 165.7, 160.6, 138.3, 137.9, 130.5, 128.9, 120.0, 119.9, 43.9, 38.2, 33.8, 31.0, 27.4, 23.7, 14.0; MS (ES+) m/z 260.2 (M + 1)· 實例761.97-1.84 (m, 2H), 1.72-1.57 (m, 2H), 1.07 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CD3〇D) 5 165.7, 160.6, 138.3, 137.9, 130.5, 128.9, 120.0, 119.9, 43.9, 38.2, 33.8, 31.0, 27.4, 23.7, 14.0; MS (ES+) m/z 260.2 (M + 1)· Example 76

2 丁基3 (2-，、氫吡啶基乙基 &gt;奎唑4 _4(讯)·_之合成 按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯曱酸置換2_胺基錢m(六氫基）乙 胺置換4-胺基苯基胺基甲酸第三_丁醋，獲得2_丁基_吵六氯 128409 -205 - 200836743 吡啶-1-基乙基 &gt;奎唑啉-4(3H)-酮（65%)，為無色液體：1H NMR (300 MHz, CDC13) 5 8.21 (dd，J = 8.1，1.2 Hz，1H)，7.76-7.58 (m，2H)， 7.46-7.38 (m5 1H)? 4.24 (t5 J = 6.6 Hz? 2H)5 2.88 (t5 J = 7.8 Hz? 2H)? 2.64 (t5 J = 6·6 Hz，2H)，2.52 (br4H)，1.89-1.77 (m，2H)，1.69-1.38 (m，8H)，0.98 (t， J = 7.5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.4, 157.5, 147.5, 134.2, 126.9, 126.7, 126.3, 120.5, 57.3, 55.2, 41.8, 35.2, 29.7, 26.1，24.3, 22.8, 14.1 ； MS (ES+) m/z 314.2 (M + 1). 實例77Synthesis of 2 butyl 3 (2-, hydropyridylethyl) quinazole 4 _4 (induction) _ according to the procedure as described in Example 56, irrelevant changes were made using o-aminobenzoic acid Substituting 2_Aminophenol m (hexahydro)ethylamine to replace 4-aminophenylaminocarbamic acid third-butyl vinegar to obtain 2_butyl_noise hexachloro 128409 -205 - 200836743 pyridin-1-yl Base &gt; quinazoline-4(3H)-one (65%) as a colorless liquid: 1H NMR (300 MHz, CDC13) 5 8.21 (dd, J = 8.1, 1.2 Hz, 1H), 7.76-7.58 (m , 2H), 7.46-7.38 (m5 1H)? 4.24 (t5 J = 6.6 Hz? 2H)5 2.88 (t5 J = 7.8 Hz? 2H)? 2.64 (t5 J = 6·6 Hz, 2H), 2.52 (br4H ), 1.89-1.77 (m, 2H), 1.69-1.38 (m, 8H), 0.98 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.4, 157.5, 147.5, 134.2, 126.9 , 126.7, 126.3, 120.5, 57.3, 55.2, 41.8, 35.2, 29.7, 26.1, 24.3, 22.8, 14.1 ; MS (ES+) m/z 314.2 (M + 1). Example 77

3-(4-溴基-2-氟苯基）-2-丁基喳唑啉-4(3H)-酮之合成 按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4-溴基-2-氟-苯胺置換 4-胺基苯基胺基甲酸第三-丁酯，獲得3-(4-溴基-2-氟苯基）_2_ 丁基喹唑啉-4(3H)-酮（29%)，為無色固體：熔點i〇2-l〇4°C ; 1Η NMR (300 MHz，CDC13) 5 8.26 (dd，J = 8·1，0·9 Ηζ，1Η)，7.82-7.68 (m， 2H)，7.54-7.43 (m，3H)，7.18 (t，J = 7.8 Hz，1H)，2_49-2·37 (m，2H)，1.68 (五重峰，J = 7·5 Hz，2H)，1.37-1.22 (m，2H)，0_85 (t，J = 7.5 Hz，3H); 13C NMR (75 MHz，CDC13) 5 161.8, 159.5, 156.3, 156.1，147.5, 135.0, 131.5, 128·8, 128.7, 127.3, 127.2, 127.0, 124.5, 124.3, 124.1，124·0, 121.0, 120.7, 120.4, 35.2, 28.8, 22.4, 13.8; MS (ES+) m/z 375.0 (Μ + 1)，377.0 (Μ + 1)· 實例78 2-丁基-3-(3-六氫吡啶-1-基丙基 &gt;奎唑啉-4(3H)-酮之合成 128409 -206- 200836743Synthesis of 3-(4-bromo-2-fluorophenyl)-2-butyloxazolyl-4(3H)-one was carried out according to the procedure as described in Example 56, with irrelevant changes, using o-amines Substituting 2-aminonicotinic acid for benzoic acid, and replacing 3-aminobutyl 4-aminophenylaminocarbamate with 4-bromo-2-fluoro-aniline to obtain 3-(4-bromo-2- Fluorophenyl)_2_butylquinazoline-4(3H)-one (29%) as a colorless solid: m.p.: </ RTI> </ RTI> </ RTI> </ RTI> NMR (300 MHz, CDC13) 5 8.26 (dd, J = 8·1,0·9 Ηζ,1Η),7.82-7.68 (m, 2H), 7.54-7.43 (m,3H), 7.18 (t,J = 7.8 Hz,1H),2_49-2·37 ( m, 2H), 1.68 (five peaks, J = 7·5 Hz, 2H), 1.37.12.22 (m, 2H), 0_85 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 161.8, 159.5, 156.3, 156.1, 147.5, 135.0, 131.5, 128·8, 128.7, 127.3, 127.2, 127.0, 124.5, 124.3, 124.1, 124·0, 121.0, 120.7, 120.4, 35.2, 28.8, 22.4, 13.8 MS (ES+) m/z 375.0 (Μ + 1), 377.0 (Μ + 1)· Example 78 2-butyl-3-(3-hexahydropyridin-1-ylpropyl) quinazoline-4 Synthesis of (3H)-ketone 128409 -206- 200836743

才女妝如貫例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及3_(六氫吡啶小基）丙 小胺置換4-胺基苯基胺基甲酸第三·丁酯，獲得厶丁基各(3· 六氫吡啶-1-基丙基 &gt;奎唑啉_4(3印_酮（65%),為無色液體· ！ H NMR (300 MHz，CDC13) 5 8.26-8.19 (m，1H)，7.74-7.58 (m，2H)， 7.45-7.37 (m3 1H)? 4.15 (t? J = 7.5 Hz? 2H)? 2.89 (t? J = 7.8 Hz? 2H)5 2.54- 2.26 (m，6H)，2.03-1.74 (m，4H)，1.65-1.35 (m，8H)，1.00 (t，J = 7·5 Hz， 3H) ； NMR (75 MHz? CDC13) 5 162.5, 157.6, 147.5, 134.1? 126.95 126.7, 126.3, 120.6, 56.2, 54.7, 42.6, 35.1，30.0, 26.1，24.6, 22.8, 14.0 ; MS (ES+) m/z 328.2 (M + 1). 實例79 3-(4-/臭基-2-氯苯基）-2-丁基tr奎嗤p林-4(3H)_酮之合成The makeup procedure was as described in Example 56, with irrelevant changes, replacing the 2-aminonicotinic acid with o-aminobenzoic acid and the 4-amino group with 3-(hexahydropyridine small) propylamine. Phenylaminocarboxylic acid, the third butyl ester, obtained by fluorenyl butyl (3 · hexahydropyridin-1-ylpropyl) quinazoline _4 (3 _ ketone (65%), is a colorless liquid! H NMR (300 MHz, CDC13) 5 8.26-8.19 (m, 1H), 7.74 - 7.58 (m, 2H), 7.45-7.37 (m3 1H)? 4.15 (t? J = 7.5 Hz? 2H)? 2.89 (t J = 7.8 Hz? 2H)5 2.54- 2.26 (m, 6H), 2.03-1.74 (m, 4H), 1.65-1.35 (m, 8H), 1.00 (t, J = 7·5 Hz, 3H); NMR (75 MHz? CDC13) 5 162.5, 157.6, 147.5, 134.1? 126.95 126.7, 126.3, 120.6, 56.2, 54.7, 42.6, 35.1, 30.0, 26.1, 24.6, 22.8, 14.0 ; MS (ES+) m/z 328.2 ( M + 1). Example 79 Synthesis of 3-(4-/odoryl-2-chlorophenyl)-2-butyltr-quinep-p--4(3H)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4_溴基_2_氣-苯胺置換 4-胺基苯基胺基甲酸第三_丁酯，獲得3-(4_溴基_2_氯苯基）_2_ 丁基邊哇琳-4(3H)-酮（24%)，為無色固體：熔點1〇9]ηι ; 1 H NMR (300 MHz, CDC13) 5 8.27 (dd5 J = 7.5, 0.6 Hz? 1H)? 7.83-7.68 (m? 3H)，7.60 (dd，J = 8.4, 2.1 Hz，1H)，7.48 (dd，J = 7.5, 7.5 Hz，1H)，7·21 (d， J = 8.4 Hz5 1HX 2.47-2.27 (m5 2H)5 1.82-1.62 (m? 2H)5 1.38-1.22 (m5 2H)3 0.85 (t，J = 7.5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 161.7, 156.2, 128409 -207- 200836743 147.5, 135.0, 134.5, 134.2, 133.6, 131.7, 131.5, 127·3, 127.2, 127·0, 124.0, 120.5, 35.1，28.8, 22·4, 13·9 ; MS (ES+) m/z 391.0 (Μ + 1)，393.0 (Μ + 1)· 實例80 3-[4-漠基-2-(三氟甲基）苯基]-2-丁基ρ奎嗤琳-4(3Η)-酮之合成According to the procedure as described in Example 56, irrelevant changes were made, replacing 2-aminonicotinic acid with o-aminobenzoic acid and 4-aminophenylamine with 4-bromo-2-oxo-aniline. The third _ butyl carboxylic acid gave 3-(4-bromo-2- chlorophenyl) 2 butyl bromo-branol-4(3H)-one (24%) as a colorless solid: melting point 1 〇 9] Ηι ; 1 H NMR (300 MHz, CDC13) 5 8.27 (dd5 J = 7.5, 0.6 Hz? 1H)? 7.83-7.68 (m? 3H), 7.60 (dd, J = 8.4, 2.1 Hz, 1H), 7.48 ( Dd, J = 7.5, 7.5 Hz, 1H), 7·21 (d, J = 8.4 Hz5 1HX 2.47-2.27 (m5 2H) 5 1.82-1.62 (m? 2H)5 1.38-1.22 (m5 2H)3 0.85 ( t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 161.7, 156.2, 128409 -207-200836743 147.5, 135.0, 134.5, 134.2, 133.6, 131.7, 131.5, 127·3, 127.2, 127· 0, 124.0, 120.5, 35.1, 28.8, 22·4, 13·9 ; MS (ES+) m/z 391.0 (Μ + 1), 393.0 (Μ + 1)· Example 80 3-[4-漠基-2 Synthesis of -(trifluoromethyl)phenyl]-2-butyl ρ 奎嗤琳-4(3Η)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4-溴基_2_三氟甲基-苯胺置換4_胺基苯基胺基曱酸第三-丁酯，獲得3_[4-溴基 -2-(三氟甲基）苯基]-2-丁基喳唑啉-4(3Η)-酮（17%)，為無色固 體：熔點 122-124°C ; 1 H NMR (300 MHz，CDC13) 5 8·25 (dd，J = 7.8, 0·9 Hz，1H)，8·01 (d，J = 2·1 Hz，1H)，7.89 (dd，J = 8.1，2·1 Hz，1H)， 7.83-7.68 (m，2H)，7.48 (ddd，卜 8.1，8.1，1·2 Hz，1H)，7.24 (d，J = 8.4 Hz， 1H)，2.44-2.16 (m，2H)，1.85-1.62 (m，2H)，1.38-1.20 (m，2H)，0·86 (t，J = 7.5 Hz, 3H) ； 13C NMR (75 MHz, CDC13) 5 162.3, 156.1, 147.5, 136.8, 135.0, 134.6, 132.8, 131.4，(q，J = 21 Hz)，129.9 (q，J = 126 Hz)，127.4, 127.2, 127.0, 124.0 (123.9)，120.3 (120.2)，35.3, 28.9, 22.4, 13.9; MS (ES+) m/z 425.0 (M + 1)3 427.0 (M + 1). 實例81 3 (4溴基2,6 一氟本基）丁基峻峻淋之合成According to the procedure as described in Example 56, irrelevant changes were made, replacing the 2-aminonicotinic acid with o-aminobenzoic acid and the 4-amino group with 4-bromo-2-trifluoromethyl-phenylamine. Phenylamino decanoic acid tert-butyl ester to give 3-[4-bromo-2-(trifluoromethyl)phenyl]-2-butyloxazoline-4(3Η)-one (17%) , as a colorless solid: melting point 122-124 ° C; 1 H NMR (300 MHz, CDC13) 5 8 · 25 (dd, J = 7.8, 0·9 Hz, 1H), 8·01 (d, J = 2· 1 Hz, 1H), 7.89 (dd, J = 8.1, 2·1 Hz, 1H), 7.83-7.68 (m, 2H), 7.48 (ddd, 4.8, 8.1, 1·2 Hz, 1H), 7.24 ( d, J = 8.4 Hz, 1H), 2.44-2.16 (m, 2H), 1.85-1.62 (m, 2H), 1.38-1.20 (m, 2H), 0·86 (t, J = 7.5 Hz, 3H) 13C NMR (75 MHz, CDC13) 5 162.3, 156.1, 147.5, 136.8, 135.0, 134.6, 132.8, 131.4, (q, J = 21 Hz), 129.9 (q, J = 126 Hz), 127.4, 127.2, 127.0 , 124.0 (123.9), 120.3 (120.2), 35.3, 28.9, 22.4, 13.9; MS (ES+) m/z 425.0 (M + 1)3 427.0 (M + 1). Example 81 3 (4 bromo 2,6 Synthesis of fluorocarbon) butyl sulphide

按照如實例56中所述之程序，施行無關緊要之改變，使 128409 -208 - 200836743 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4-溴基-2,6-二氟-苯胺 置換4_胺基苯基胺基甲酸第三-丁酯，獲得3-(4·溴基-2,6-二氟 苯基）-2-丁基4唑琳-4(3H)-酮（28%)，為無色固體：熔點145-147 °C ; 1H NMR (300 MHz，CDC13) 5 8.29-8.23 (m，1H)，7.83-7.68 (m，2H)， 7.49 (ddd，J = 7.5, 7.5, 1·2 Hz，1H)，7·37-7_29 (m，2H)，2.45 (t，J = 7.5 Hz， 2H)，1.72 (五重峰，J = 7.5 Hz，2H)，1.39-1.23 (m，2H)，0.86 (t，J = 7.5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 161.1，160.2 (d，J = 21 Hz)， 156.8 (d，J = 18 Hz)，156.0, 147.5, 135.2, 127.4, 127.3, 127.1，123.8 (t，J = 45 Hz)，120.2, 116.8 (d，J = 15 Hz)，116.5 (d，J = 15 Hz)，114.1 (td，J = 66 Hz)，34.8, 28.6, 22.3, 13.8 ; MS (ES+) m/z 393.0 (M + 1)，395.0 (M + 1). 實例82 3-(4-漠基-2-甲基苯基）-2-丁基p奎唾琳-4(3H)-酮之合成According to the procedure as described in Example 56, an insignificant change was made such that 128409-208 - 200836743 replaced 2-aminonicotinic acid with o-aminobenzoic acid, and 4-bromo-2,6-difluoro- Replacement of 4-aminophenylaminocarbamic acid tert-butyl ester with aniline to give 3-(4.bromo-2,6-difluorophenyl)-2-butyl-4-oxalin-4(3H)-one (28%) as colorless solid: mp 145-147 ° C; 1H NMR (300 MHz, CDC13) 5 8.29-8.23 (m,1H), 7.83-7.68 (m,2H), 7.49 (ddd, J = 7.5 , 7.5, 1·2 Hz, 1H), 7·37-7_29 (m, 2H), 2.45 (t, J = 7.5 Hz, 2H), 1.72 (five peaks, J = 7.5 Hz, 2H), 1.39- 1.23 (m, 2H), 0.86 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 161.1, 160.2 (d, J = 21 Hz), 156.8 (d, J = 18 Hz), 156.0, 147.5, 135.2, 127.4, 127.3, 127.1, 123.8 (t, J = 45 Hz), 120.2, 116.8 (d, J = 15 Hz), 116.5 (d, J = 15 Hz), 114.1 (td, J = 66 Hz), 34.8, 28.6, 22.3, 13.8; MS (ES+) m/z 393.0 (M + 1), 395.0 (M + 1). Example 82 3-(4-Mosyl-2-methylphenyl) Synthesis of -2-butyl p-quineline-4(3H)-one

按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及4-溴基_2_甲基-苯胺置 換4-胺基苯基胺基甲酸第三-丁酯，獲得3-(4-溴基-2-曱基苯 基）·2-丁基喳唑啉-4(3H)-酮（46%)，為無色固體：熔點in-113 °C ； ^ NMR (300 MHz? CDC13) 5 8.27 (d5 J = 7.8 Hz? 1H)? 7.82-7.68 (m，2H)，7.56 (s，1H)，7.53-7.43 (m，2H)，7.04 (d，J = 8·4 Hz，1H)，2.33 (t， J = 7.5 Hz，2H)，2.09 (s，3H)，1.68 (五重峰，J = 7·5 Hz，2H)，1.37-1.20 (m，2H)，0.84 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 6 161.8, 156.7, 147.7, 138.1，135.7, 134.8, 134.5, 130.7, 130.0, 127.2, 127.2, 126.8, 123.5, 120.6, 35.2, 28.9, 22.4, 17.6, 13.9 ; MS (ES+) m/z 371.0 (M + 1)， 128409 -209- 200836743 373.0 (Μ + 1). 實例83According to the procedure as described in Example 56, an insignificant change was made, replacing the 2-aminonicotinic acid with o-aminobenzoic acid and the 4-aminophenyl group with 4-bromo-2-methyl-aniline. Third-butyl carbamic acid ester, 3-(4-bromo-2-indenylphenyl)-2-butytooxazolyl-4(3H)-one (46%) as a colorless solid: melting point In-113 °C ; ^ NMR (300 MHz? CDC13) 5 8.27 (d5 J = 7.8 Hz? 1H)? 7.82-7.68 (m, 2H), 7.56 (s, 1H), 7.53-7.43 (m, 2H) , 7.04 (d, J = 8·4 Hz, 1H), 2.33 (t, J = 7.5 Hz, 2H), 2.09 (s, 3H), 1.68 (five peaks, J = 7·5 Hz, 2H), 1.37-1.20 (m, 2H), 0.84 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 6 161.8, 156.7, 147.7, 138.1, 135.7, 134.8, 134.5, 130.7, 130.0 , 127.2, 127.2, 126.8, 123.5, 120.6, 35.2, 28.9, 22.4, 17.6, 13.9; MS (ES+) m/z 371.0 (M + 1), 128409 -209-200836743 373.0 (Μ + 1). Example 83

3-(4_&gt;臭基-2,6-一甲基苯基）-2-丁基ρ奎。坐琳_4(3Η)_酮之合成 按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基笨甲酸置換2-胺基菸驗酸，及4_溴基_2,6·二甲基-苯 胺置換4-胺基苯基胺基甲酸第三-丁酯，獲得3_(4_溴基-2,6•二 甲基苯基）-2-丁基喳唑啉_4(3Η)-酮（29%)，為無色固體：熔點 94-96°C ; 1 H NMR (300 MHz，CDC13) δ 8,31-8.25 (m，1Η)，7.82-7.70 (m， 2H)，7.48 (ddd，J = 7.5, 7.5, 1.2 Hz，1H)，7.39 (s，2H)，2.56 (t，卜 7.5 Hz， 2UI 1.71 ( i ί ^ 5 J = 7.5 Hz5 2H)3 1.38-1.23 (m5 2H)5 0.86 (t5 J = 7.53-(4_&gt; odoryl-2,6-monomethylphenyl)-2-butyl ρ 奎. The synthesis of lysine_4(3Η)-ketone was carried out according to the procedure described in Example 56, with irrelevant changes, replacing the 2-amino niacin acid with o-amino benzoic acid, and 4-bromo-2, 6·Dimethyl-aniline displaces 4-aminobutyl 4-aminophenylaminocarbamate to obtain 3-(4-bromo-2,6•dimethylphenyl)-2-butyloxazoline 4(3Η)-ketone (29%) as colorless solid: m.p. 94-96°C; 1 H NMR (300 MHz, CDC13) δ 8,31-8.25 (m,1 Η), 7.82-7.70 (m, 2H ), 7.48 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.39 (s, 2H), 2.56 (t, 7.5 Hz, 2UI 1.71 (i ί ^ 5 J = 7.5 Hz5 2H)3 1.38-1.23 (m5 2H)5 0.86 (t5 J = 7.5

Hz，3H); 13CNMR (75 MHz，CDC13) 5 161.3, 156.6, 147.8, 137.7, 134.9, 134.8, 132.0, 127.3, 126.8, 123.1，120.7, 34.5, 28.5, 22.5, 17.8, 13.9 ; MS (ES+) m/z 385·0 (M +1)，387 〇 (M + &amp; 實例84 2-丁基-3-(3-四氫吡咯小基丙基）峻唑啉_4(3H)_嗣之合成Hz,3H); 13CNMR (75 MHz, CDC13) 5 161.3, 156.6, 147.8, 137.7, 134.9, 134.8, 132.0, 127.3, 126.8, 123.1, 120.7, 34.5, 28.5, 22.5, 17.8, 13.9 ; MS (ES+) m /z 385·0 (M +1), 387 〇(M + &amp; Example 84 2-butyl-3-(3-tetrahydropyrrolidinylpropyl) thiazoline-4(3H)_嗣 Synthesis

按照如實例56中所述之程序，施行無關緊要之改變，使 用#月安基苯甲酉夂置換2-胺基於驗酸，及3_(四氫p比略]_基）丙 小胺置換4-胺基苯基胺基甲酸第三_丁酯，獲得孓丁基斗ρ- ΐ 28409 -210- 200836743 四氫吡咯-1-基丙基）喹唑啉_4(3H)·酮（51%)，為無色液體：1Η NMR (300 MHz5 CDC13) δ 8.23 (d5 J = 6.8 Hz? 1H)? 7.73-7.65 (m, 1H)? 7.60 (d，J = 8.4 Hz，1H)，7.45-7.36 (m，1H)，4.17 (t，J = 7.5 Hz，2H)，2·87 (t，J = 7.8 Hz，2H)，2.61-2.45 (m，6H)，2·03·1·69 (m，8H)，1.55-1.41 (m， 2H)，0.98 (t，J = 7.5 Hz，3H); 13 C NMR (75 MHz，CDC13) 5 162.4, 157.4, 147.4, 134.0, 126.8, 126.6, 126.2, 120.5, 54.1，53.3, 42.4, 34.9, 29.8, 28.1， 23.5, 22.7, 13.9 ; MS (ES+) m/z 314.2 (M + 1)· 實例85According to the procedure as described in Example 56, an insignificant change was made, using #月安基苯苯酉夂 to replace 2-amine based on acid detection, and 3_(tetrahydro-p-slightly)-based propylamine replacement 4 -Aminobutylaminocarbamic acid tert-butyl ester to obtain hydrazine butyl ρ- ΐ 28409 -210- 200836743 tetrahydropyrrole-1-ylpropyl)quinazoline _4(3H)·one (51% ), as a colorless liquid: 1 NMR (300 MHz 5 CDC13) δ 8.23 (d5 J = 6.8 Hz? 1H)? 7.73-7.65 (m, 1H)? 7.60 (d, J = 8.4 Hz, 1H), 7.45-7.36 ( m,1H), 4.17 (t, J = 7.5 Hz, 2H), 2·87 (t, J = 7.8 Hz, 2H), 2.61-2.45 (m, 6H), 2·03·1·69 (m, 8H), 1.55-1.41 (m, 2H), 0.98 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.4, 157.4, 147.4, 134.0, 126.8, 126.6, 126.2, 120.5, 54.1, 53.3, 42.4, 34.9, 29.8, 28.1, 23.5, 22.7, 13.9; MS (ES+) m/z 314.2 (M + 1)· Example 85

2-丁基-3-[2-(l-甲基四氫吡咯_2_基）乙基]P奎唑啉-4(3H)_g同之合成 按照如實例56中所述之程序，施行無關緊要之改變，使 用鄰胺基苯甲酸置換2-胺基菸鹼酸，及2-(2-胺基乙基）-1-甲基 二氫吡咯置換4-胺基苯基胺基甲酸第三_ 丁酯，獲得2-丁基 -3-[2-(l-曱基四氫吡咯-2-基）乙基]喹唑啉_4(3H)__ (32%)，為無 色液體：1 H NMR (300 MHz，CDC13) 5 8·23 (dd，J = 7.8, 1·2 Hz，1H)， 7.76-7.59 (m，2H)，7.46-7.38 (m，1H)，4.29-3.99 (m，2H)，3.19-3.07 (m， 1H)，2.83 (dd，J = 9·0, 6.3 Hz, 2H)，2.39 (s，3H)，2.38-2.17 (m，2H)， 2.15-2.00 (m，2H)，1.92-1.63 (m，6H)，1.58-1.42 (m，2H)，0.99 (t，J = 7.5 Hz，3H); 13C NMR (75 MHz，CDC13) 6 162.4, 157.2, 147.5, 134.2, 126.9, 126.7, 126.4, 120.5, 63.99, 57.2, 41.2, 40.6, 35.0, 32.2, 30.2, 29.9, 22.8, 22.2, 14.0 ； MS (ES+) m/z 314.2 (M + 1). 實例86 2-丁基-3-(2-氣基-4_嗎福琳-4-基苯基）峻σ坐淋-4(3H)-S同之合成 128409 -211- 2008367432-butyl-3-[2-(l-methyltetrahydropyrrole-2-yl)ethyl]P quinazoline-4(3H)_g was synthesized according to the procedure as described in Example 56. Insignificant change, replacement of 2-aminonicotinic acid with o-aminobenzoic acid, and replacement of 4-aminophenylaminocarboxylic acid with 2-(2-aminoethyl)-1-methyldihydropyrrole Tri-butyl ester, 2-butyl-3-[2-(l-fluorenyltetrahydropyrrol-2-yl)ethyl]quinazoline_4(3H)__ (32%) was obtained as a colorless liquid: 1 H NMR (300 MHz, CDC13) 5 8·23 (dd, J = 7.8, 1·2 Hz, 1H), 7.76-7.59 (m, 2H), 7.46-7.38 (m, 1H), 4.29-3.99 ( m, 2H), 3.19-3.07 (m, 1H), 2.83 (dd, J = 9·0, 6.3 Hz, 2H), 2.39 (s, 3H), 2.38-2.17 (m, 2H), 2.15-2.00 ( m, 2H), 1.92-1.63 (m, 6H), 1.58-1.42 (m, 2H), 0.99 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 6 162.4, 157.2, 147.5, 134.2, 126.9, 126.7, 126.4, 120.5, 63.99, 57.2, 41.2, 40.6, 35.0, 32.2, 30.2, 29.9, 22.8, 22.2, 14.0; MS (ES+) m/z 314.2 (M + 1). Example 86 2- Butyl-3-(2-carbyl-4_ifosin-4-ylphenyl) sigma-supplied-4(3H)-S with the same synthesis 128409 -211- 20083 6743

Ο 使3-(4-溴基_2-氯苯基）-2-丁基喹唑啉-4(3Η)，（〇·353克，〇 9〇 宅莫耳）、嗎福啉（0.118毫升，1.35毫莫耳）及2,2，_雙（二苯基膦 基）-1，Γ-聯莕（〇·〇84克，0.135毫莫耳）在甲苯（1〇毫升）中之經攪 拌溶液以氮起泡十五分鐘。添加參（二苯亞甲基丙酮）二鈀⑼ (0.041毫克，0.045毫莫耳）與第三叮醇鈉（〇.173克，18毫莫 耳）。使反應混合物以氮再起泡十五分鐘，然後裝上冷凝器， 亚於氮氣下加熱至回流，歷經十六小時。使混合物蒸發至 乾涸。使殘留物接受管柱層析（在己烷中之5〇%醋酸乙酯）， 獲得2-丁基各(2-氯基斗嗎福啉斗基苯基）ρ奎唑啉_4(3Η),，為 無色固體（0·120 克，53%):熔點 153_155r ; lH NMR (3〇〇 驗， CDC13) δ 8.28-8.22 (m5 1H)? 7.80-7.67 (m? 2H)? 7.49-7.41, 1H)5 7.30-7.12 (m? 3H)? 3.90 (t5 J = 4.8 Hz5 4H)5 3.31 (t5 J = 4.8 Hz5 4H)? 2.48-2.23 (m5Ο 3-(4-Bromo-2-chlorophenyl)-2-butylquinazoline-4(3Η), (〇·353g, 〇9〇家莫耳), morphine (0.118 ml) , 1.35 millimolar) and 2,2,_bis(diphenylphosphino)-1, hydrazine-hydrazine (〇·〇 84 g, 0.135 mmol) stirred in toluene (1 mL) The solution was bubbled with nitrogen for fifteen minutes. Add gin (diphenylmethyleneacetone) dipalladium (9) (0.041 mg, 0.045 mmol) with sodium third sterol (〇.173 g, 18 mmol). The reaction mixture was re-foamed with nitrogen for fifteen minutes, then charged to a condenser and heated to reflux under nitrogen for 16 hours. The mixture was allowed to evaporate to dryness. The residue was subjected to column chromatography (5 〇% ethyl acetate in hexane) to give 2-butyl-(2-chloro-bupropion porphyrin-phenyl) quinazoline _4 (3 Η ), as a colorless solid (0·120 g, 53%): melting point 153_155r; lH NMR (3 , test, CDC13) δ 8.28-8.22 (m5 1H)? 7.80-7.67 (m? 2H)? 7.49-7.41 , 1H)5 7.30-7.12 (m? 3H)? 3.90 (t5 J = 4.8 Hz5 4H)5 3.31 (t5 J = 4.8 Hz5 4H)? 2.48-2.23 (m5

2H), 1.83 1.66 (m，2H)，1.39-U9 (m，2H)，0.85 (t，卜 7·5 Hz，3H) ; MS (ES+) m/z，398.1 (M + 1)，400 1 (M + υ 實例87 丁基3 [4馬私啉冰基(三氟甲基）苯基]喹唑啉·4()Η)-嗣之 按照如實例86中所述2H), 1.83 1.66 (m, 2H), 1.39-U9 (m, 2H), 0.85 (t, 7.5 Hz, 3H); MS (ES+) m/z, 398.1 (M + 1), 400 1 (M + υ Example 87 butyl 3 [4 horse porphyrin yl (trifluoromethyl)phenyl] quinazoline · 4 () Η) - 嗣 as described in Example 86

之程序，施行無關緊要之改變，使 128409 -212- 200836743 用3·[4-溴基-2-(三氟甲基）苯基]-2-丁基喳唑啉-4(3H)-酮置換 3_(4_溴基-2-氣苯基）-2-丁基p奎唑琳-4(3H)-酮，獲得2-丁基-3-[4-嗎福淋_4_基-2-(三氟甲基）苯基]4哇琳-4(3H)-_ (45%)，為無色 固體：熔點 180-182°C ; iHNMR(300 MHz，CDCl3)^ 8.29-8.23 (m， 1H)，7.80-7.67 (m，2H)，7.50-7.41 (m，1H)，7· 17 (d，J = 8·7 Hz，1Η)，7·06 (d，J = 2·7 Hz，1H)，6·92 (dd，J = 8_7, 2.7 Hz，1H)，3·88 (t，J = 4.8 Hz，4H)， 3.26 (t，J = 4·8 Hz，4H)，2.53-2.31 (m，2H)，1.80-1.64 (m，2H)，1.38-1.21 (m，2H)，0.85 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 162.2, 157.6, 152.6, 147.6, 134.7, 133.5, 130.4, 127.3, 127.1，126.6, 125.9, 120.7, 116.3, 114.4, 66.7, 48.4, 35.2, 28.9, 22.5, 13.9 ; MS (ES+) m/z 432.2 (M + 1)· 實例88 2-丁基-3-(2,6·二氟-4-嗎福4 -4-基苯基奎σ坐琳·4(3η)-_之合成The procedure, the implementation of the insignificant change, made 128.409-212-200836743 with 3·[4-bromo-2-(trifluoromethyl)phenyl]-2-butyloxazoline-4(3H)-one Replacement of 3_(4-bromo-2-pyrophenyl)-2-butyl p-quinazoline-4(3H)-one to give 2-butyl-3-[4-? 2-(Trifluoromethyl)phenyl]4 wowolin-4(3H)-- (45%) as colorless solid: m.p. 180-182°C; iHNMR (300 MHz, CDCl3)^ 8.29-8.23 (m , 1H), 7.80-7.67 (m, 2H), 7.50-7.41 (m, 1H), 7· 17 (d, J = 8·7 Hz, 1Η), 7·06 (d, J = 2·7 Hz , 1H), 6.92 (dd, J = 8_7, 2.7 Hz, 1H), 3·88 (t, J = 4.8 Hz, 4H), 3.26 (t, J = 4·8 Hz, 4H), 2.53- 2.31 (m, 2H), 1.80- 1.64 (m, 2H), 1.38-1.21 (m, 2H), 0.85 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.2 , 157.6, 152.6, 147.6, 134.7, 133.5, 130.4, 127.3, 127.1, 126.6, 125.9, 120.7, 116.3, 114.4, 66.7, 48.4, 35.2, 28.9, 22.5, 13.9; MS (ES+) m/z 432.2 (M + 1)· Example 88 Synthesis of 2-butyl-3-(2,6·difluoro-4-isof 4-4-ylphenyl quinone sylphine 4(3η)-_

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴基-2,6-二氟苯基）-2-丁基峻唑淋-4(3Η)-酮置換3-(4-溴 基-2-氯苯基）-2-丁基唆嗤p林-4(3H)-酮，獲得2-丁基-3-(2,6-二氣 -4·嗎福琳-4-基苯基 &gt;奎唾琳-4(3Η)·_ (95%)，為無色固體：溶 點 168-170 °C ; 4 NMR (300 MHz，CDC13) 5 8.29-8.23 (m，1Η)， 7.80-7.67 (m，2H)，7.50-7.50 (m，1H)，6.60-6.50 (m，2H)，3.87 (t，J = 4·8 Hz，4H)，3.25 (t，J = 4·8 Hz，4H)，2.52 (t，J = 7·5 Hz, 2H)，1.69 (五重峰 5 128409 -213- 200836743 J = 7.5 Hz，2H)，1.40-1.25 (m，2H)，0.86 (t，J = 7.5 Hz，3H); 13C NMR (75 MHz，CDC13) 5 161.8, 160.9 (d，J = 27 Hz)，157.6 (d，J = 27 Hz)，157.5, 153.1 (t，J = 48 Hz)，147.6, 134.8, 127.3, 127.2, 126.8, 120.5, 104.5，(t，J = 72 Hz)，98.2 (d，J = 9 Hz)，97.9 (d，J = 9 Hz)，66.5, 47.8, 35.0, 28.7, 22.4, 13.9 ； MS (ES+) m/z 400.2 (M + 1). 實例89 2-丁基-3-(2-甲基-4-嗎福4 -4-基苯基）p奎唾4 -4(3Η)-ί同之合成According to the procedure as described in Example 86, irrelevant changes were made using 3-(4-bromo-2,6-difluorophenyl)-2-butylrimazole--4(3Η)-one to replace 3- (4-bromo-2-chlorophenyl)-2-butylindole p--4(3H)-one, 2-butyl-3-(2,6-di-gas-4·fofolin 4--4-Phenylphenyl&gt;Querazine-4(3Η)·_ (95%), as a colorless solid: melting point 168-170 °C; 4 NMR (300 MHz, CDC13) 5 8.29-8.23 (m, 1Η), 7.80-7.67 (m, 2H), 7.50-7.50 (m, 1H), 6.60-6.50 (m, 2H), 3.87 (t, J = 4·8 Hz, 4H), 3.25 (t, J = 4·8 Hz, 4H), 2.52 (t, J = 7·5 Hz, 2H), 1.69 (five peaks 5 128409 -213- 200836743 J = 7.5 Hz, 2H), 1.40-1.25 (m, 2H), 0.86 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 161.8, 160.9 (d, J = 27 Hz), 157.6 (d, J = 27 Hz), 157.5, 153.1 (t, J = 48 Hz), 147.6, 134.8, 127.3, 127.2, 126.8, 120.5, 104.5, (t, J = 72 Hz), 98.2 (d, J = 9 Hz), 97.9 (d, J = 9 Hz), 66.5, 47.8, 35.0, 28.7, 22.4, 13.9; MS (ES+) m/z 400.2 (M + 1). Example 89 2-butyl-3-(2-methyl-4-? )P Kui saliva 4 -4 (3Η) - ί同的合成

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴基-2-甲基苯基）-2-丁基喳唑啉-4(3Η)-酮置換3-(4-溴基 -2-氯苯基）-2-丁基π奎唾淋-4(3H)-i同，獲得2-丁基-3-(2-甲基-4-嗎 福淋-4-基苯基 &gt;奎唾琳-4(3H)_酮（85%)，為無色固體：嫁點 168-170°C ; 1H NMR (300 MHz，CDC13) 5 8.27 (dcU = 7.5, 1.2 Hz，1H)， 7.80-7.68 (m，2H)，7.49-7.41 (m，1H)，7·03 (d，J = 8·1 Hz，1H)，6.91-6.83 (m5 2H)5 3.88 (t5 J = 4.8 Hz? 4H)? 3.24 (t5 J = 4.8 Hz5 4H)? 2.38 (t? J = 7.5 Hz，2H)，2.06 (s，3H)，1.69 (五重峰，J = 7·5 Hz，2H)，1.37-1.20 (m，2H)， 0.83 (t，J = 7·5 Hz，3H) ; 13C NMR (75 MHz，CDC13) 5 162.4, 158.0, 151.8, 147.8, 136.3, 134.5, 128.9, 128.2, 127.2, 127.1，126.5, 120.9, 117.7, 114.1，67.0, 49.0, 35.3, 29.1，22.5, 18.2, 13.9; MS (ES+) m/z 378.2 (M + 1)· 實例90 2·丁基-3-(2,6-二甲基-4·嗎福4 -4_基苯基)峻唾琳_4(3H)-_之合成 128409 •214- 200836743Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromo-2-methylphenyl)-2-butyloxazoline-4(3Η)-one to replace 3- (4-Bromo-2-chlorophenyl)-2-butyl π quinidine--4(3H)-i, to give 2-butyl-3-(2-methyl-4-? 4-Phenylphenyl&gt;Querazine-4(3H)-one (85%) as a colorless solid: 168-170 ° C; 1H NMR (300 MHz, CDC13) 5 8.27 (dcU = 7.5, 1.2 Hz, 1H), 7.80-7.68 (m, 2H), 7.49-7.41 (m, 1H), 7·03 (d, J = 8·1 Hz, 1H), 6.91-6.83 (m5 2H) 5 3.88 (t5 J = 4.8 Hz? 4H)? 3.24 (t5 J = 4.8 Hz5 4H)? 2.38 (t? J = 7.5 Hz, 2H), 2.06 (s, 3H), 1.69 (five peaks, J = 7·5 Hz, 2H), 1.37-1.20 (m, 2H), 0.83 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 162.4, 158.0, 151.8, 147.8, 136.3, 134.5, 128.9, 128.2 , 127.2, 127.1, 126.5, 120.9, 117.7, 114.1, 67.0, 49.0, 35.3, 29.1, 22.5, 18.2, 13.9; MS (ES+) m/z 378.2 (M + 1) · Example 90 2 · Butyl-3- Synthesis of (2,6-dimethyl-4·folf 4 -4-ylphenyl) Jun Salin _4(3H)-_ Synthesis 128409 •214- 200836743

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴基-2,6-二甲基笨基）_2_丁基喳唑啉_4(3H)_酮置換3-(4-溴基-2-氯苯基）-2-丁基喹唑啉_4(3H)_酮，獲得2_ 丁基-3-(2,6-二 甲基-4-嗎福淋-4-基苯基）邊唾P林-4(3H)-酮（90%)，為無色固 體：熔點 184-185°C ; 1 H NMR (3〇〇 MHz, CDC13) 3 8.29 (d，J = 7·8 Hz， 1H)，7.81-7.68 (m，2H)，7.49-7.41 (m，1H)，6.74 (s，2H)，3.88 (t，J = 4.8 Hz， 4H)，3.22 (t，J = 4.8 Hz，4H)，2.31 (t5 J = 8.1 Hz，2H)，2.02 (s，6H)，1.69 (五重峰，J = 7.8 Hz，2H)，1.38-1.22 (m，2H)，0.86 (t，J = 7·5 Hz，3H); 13C NMR (75 MHz, CDC13) 6 161.8，157.9，151.4，147.9，135.9，134.5, 127.7，127.3，127.1，126.4，120.9，115.7, 67.0, 49.0, 34.6, 28.6, 22.5，18.4, 14.0 ； MS (ES+) m/z 392.2 (M + 1). 實例91 2-丁基-3-(2-氟基-4-嗎福琳·4-基苯基）峻唑淋-4(3H)-酮之合成According to the procedure as described in Example 86, an insignificant change was made using 3-(4-bromo-2,6-dimethylphenyl)-2-butyloxazoline-4(3H)-one. 3-(4-bromo-2-chlorophenyl)-2-butylquinazoline-4(3H)-one to give 2-butyl-3-(2,6-dimethyl-4-?淋-4-ylphenyl) acenaphthyl P--4(3H)-one (90%) as colorless solid: mp 184-185 ° C; 1 H NMR (3 〇〇MHz, CDC13) 3 8.29 (d , J = 7·8 Hz, 1H), 7.81-7.68 (m, 2H), 7.49-7.41 (m, 1H), 6.74 (s, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.22 ( t, J = 4.8 Hz, 4H), 2.31 (t5 J = 8.1 Hz, 2H), 2.02 (s, 6H), 1.69 (five peaks, J = 7.8 Hz, 2H), 1.38-1.22 (m, 2H) , 0.86 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 6 161.8, 157.9, 151.4, 147.9, 135.9, 134.5, 127.7, 127.3, 127.1, 126.4, 120.9, 115.7, 67.0, 49.0, 34.6, 28.6, 22.5, 18.4, 14.0; MS (ES+) m/z 392.2 (M + 1). Example 91 2-butyl-3-(2-fluoro-4-phenionin-4-yl Synthesis of phenyl) thiazolyl-4(3H)-one

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4·溴基-2-氟苯基）-2-丁基喹唑啉_4(3H)_酮置換3_(4_溴基_2· 氣苯基&gt;2-丁基喳唑啉-4(3H)-_，獲得2-丁基各(2-氟基·4-嗎福According to the procedure as described in Example 86, irrelevant changes were made using 3-(4.bromo-2-fluorophenyl)-2-butylquinazoline-4(3H)-one to replace 3_(4 _Bromo 2·Phenylphenyl>2-butyloxazoline-4(3H)-_, 2-butyl each (2-fluoro-4-isof)

128409 -215- 200836743 °C ； !H NMR (300 MHz? CDC13) δ 8.26 (dd5 J = 7.85 1.2 Hz? 1H)? 7.80-7.67 (m，2H)，7.49-7.41 (m，1H), 7.16-7.07 (m, 1H)，6.82-6.71 (m， 2H)，3.88 (t，J = 4.8 Hz，4H)，3.25 (t5 J = 4.8 Hz，4H)，2.54-2.45 (m，2H)， 1.68 (五重峰，J = 7·5 Hz，2H)，1.36-1.22 (m，2H)，0.84 (t，J = 7.5 Hz， 3H) ; 13 C NMR (75 MHz，CDC13) 5 162.4, 160.2, 157.8, 156.9, 153.4 (d， J = 36 Hz)，147.6, 134.7, 130.5 (d，J = 9 Hz)，127.2, 127.1，126.7, 120.7, 115.5 (d，J = 57 Hz)，111.0 (d5 J = 12 Hz)，102.9 (d，J = 96 Hz)，66.7, 48.3, 35.3, 29.0, 22.4, 13.9 ; MS (ES+) m/z 382.2 (M + 1). 實例92128409 -215- 200836743 °C ; !H NMR (300 MHz? CDC13) δ 8.26 (dd5 J = 7.85 1.2 Hz? 1H)? 7.80-7.67 (m, 2H), 7.49-7.41 (m, 1H), 7.16- 7.07 (m, 1H), 6.82-6.71 (m, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.25 (t5 J = 4.8 Hz, 4H), 2.54-2.45 (m, 2H), 1.68 ( Wufeng, J = 7·5 Hz, 2H), 1.36-1.22 (m, 2H), 0.84 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.4, 160.2, 157.8 , 156.9, 153.4 (d, J = 36 Hz), 147.6, 134.7, 130.5 (d, J = 9 Hz), 127.2, 127.1, 126.7, 120.7, 115.5 (d, J = 57 Hz), 111.0 (d5 J = 12 Hz), 102.9 (d, J = 96 Hz), 66.7, 48.3, 35.3, 29.0, 22.4, 13.9; MS (ES+) m/z 382.2 (M + 1). Example 92

3-(4-胺基苯基）-2-丁基-7-甲基嘧吩并[3,2-d]嘧啶-4(3H)-酮之合成 按照如實例2中所述之程序，施行無關緊要之改變，使 用2-丁基-7-甲基-4H-嘧吩并[3,2-d][l，3]吟畊-4_酮置換2-丁基 -4H-3，1-苯并噚畊-4-酮，及1，4-苯二胺置換1，3-苯二胺，獲得3-(4-胺基苯基）-2-丁基-7-甲基嘧吩并[3,2-d]嘧啶-4(3H)-酮（37%)，為 無色固體：熔點 113-114°C ; 1H NMR (300 MHz, CDC13) 5 7.41 (s， 1H)，6·99 (d，J = 8.4 Hz，2H)，6.81 (d，J = 8.4 Hz，2H)，2·48 (t，J = 7.5 Hz， 2H)，2.42 (s，3H)，1.67 (五重峰，J = 7.5 Hz，2H)，1.34-1.20 (m，2H)，0.83 (t，J = 7.5 Hz, 3H) ; 13C NMR (75 MHz，CDC13) 5 159.4, 159.3, 147.1， 134.1，129.3, 128.9, 127.5, 121.4, 115.9, 35.3, 29.2, 22.3, 13.8, 12.9 ; MS (ES+) m/z 314.1 (M + 1). 實例93 2-丁基各{4-[2-(苯氧基甲基）嗎福啉-4-基]苯基}喳唑啉-4(3H)- 128409 -216- 200836743 酮之合成Synthesis of 3-(4-aminophenyl)-2-butyl-7-methylsulfonio[3,2-d]pyrimidin-4(3H)-one according to the procedure as described in Example 2, Inconsistent changes were made by replacing 2-butyl-4H-3 with 2-butyl-7-methyl-4H-sulfeno[3,2-d][l,3]indole-4-one. 1-benzoindole-4-one, and 1,4-phenylenediamine in place of 1,3-phenylenediamine to obtain 3-(4-aminophenyl)-2-butyl-7-methylpyrimidine Benzo[3,2-d]pyrimidin-4(3H)-one (37%) as colorless solid: m.p.: 113-114 ° C; 1H NMR (300 MHz, CDC13) 5 7.41 (s, 1H),6 · 99 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H), 2·48 (t, J = 7.5 Hz, 2H), 2.42 (s, 3H), 1.67 (five Peak, J = 7.5 Hz, 2H), 1.34-1.20 (m, 2H), 0.83 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 159.4, 159.3, 147.1, 134.1, 129.3, 128.9, 127.5, 121.4, 115.9, 35.3, 29.2, 22.3, 13.8, 12.9 ; MS (ES+) m/z 314.1 (M + 1). Example 93 2-butyl each {4-[2-(phenoxymethyl) Ketoprofen-4-yl]phenyl}oxazoline-4(3H)-128409 -216- 200836743 Synthesis of ketone

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）·2-丁基喳唑啉_4(3H)_酮置換3_(4_溴基_2_氯苯 基）-2-丁基峻唾琳-4(3H)-酮，及2-(苯氧基甲基）嗎福啉置換嗎 福琳’獲得2-丁基-3-{4-[2-(苯氧基甲基）嗎福啉_4_基]苯基卜奎 吐 4 -4(3H)-_ (15%)，為無色固體：熔點 88_9〇。〇 ; 1 η nmR (300 MHz5 CDC13) δ 8.26 (d5 J = 7.5 Hz5 1H)5 7.79-7.67 (m? 2H)? 7.49-7.41 (m5 1H)，7.35-7.25 (m，2H)，7.18-6.92 (m，7H)，4.20-4.02 (m，4H)，3.89 (td，J = 11.4, 2.7 Hz，1H)，3.76 (d，J = 11.7 Hz，1H)，3.54 (d，J = 11.4 Hz，1H)，3·02 (td，J = 11.4, 2·7 Hz，1H)，2.92-2.80 (m，1H)，2.48 (t，J = 7.5 Hz，2H)， 1.73-1.60 (m，2H)，1.34-1.20 (m，2H)，0·83 (t，J = 7.5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 162.9, 158.7, 158.1，151.5, 134.6, 129.7, 129.1，129.0, 127.2, 127.0, 126.6, 121.4, 120.8, 116.6, 116·4, 114.7, 74.1，68.9, 66.8, 51.1， 48.6, 35·7, 29.5, 22.5, 13·9 ; MS (ES+) m/z 470.2 (M + 1). 實例94 2-丁基-3-(4-{[(2,2_二甲基-1，3-二氧伍圜冰基）甲基]胺基}苯基） 喳唑啉-4(3H)-酮之合成Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)-2-butyrazoline-4 (3H)-one to replace 3-(4-bromo-2) _Chlorophenyl)-2-butylristorin-4(3H)-one, and 2-(phenoxymethyl)morphine replacement of phofenlin's 2-but-3-{4-[2 -(phenoxymethyl)morpholine_4_yl]phenyl buckypt 4 -4(3H)-- (15%) as a colorless solid: mp. 〇; 1 η nmR (300 MHz5 CDC13) δ 8.26 (d5 J = 7.5 Hz5 1H)5 7.79-7.67 (m? 2H)? 7.49-7.41 (m5 1H), 7.35-7.25 (m, 2H), 7.18-6.92 (m,7H), 4.20-4.02 (m,4H), 3.89 (td, J = 11.4, 2.7 Hz, 1H), 3.76 (d, J = 11.7 Hz, 1H), 3.54 (d, J = 11.4 Hz, 1H),3·02 (td, J = 11.4, 2·7 Hz, 1H), 2.92-2.80 (m, 1H), 2.48 (t, J = 7.5 Hz, 2H), 1.73-1.60 (m, 2H) , 1.34-1.20 (m, 2H), 0·83 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.9, 158.7, 158.1, 151.5, 134.6, 129.7, 129.1, 129.0, 127.2, 127.0, 126.6, 121.4, 120.8, 116.6, 116·4, 114.7, 74.1, 68.9, 66.8, 51.1, 48.6, 35·7, 29.5, 22.5, 13·9 ; MS (ES+) m/z 470.2 (M + 1). Example 94 2-Butyl-3-(4-{[(2,2-dimethyl-1,3-dioxasulfanyl)methyl]amino}phenyl) oxazoline Synthesis of -4(3H)-ketone

按照如實例86中所述之程序，施行無關緊要之改變，使 128409 -217- 200836743 用3-(4-溴苯基）-2-丁基喹唑啉-4(3H)-酮置換3-(4-溴基-2-氯苯 基）-2-丁基^奎唾琳-4(3H)-酮，及2,2-二甲基-1，3_二氧伍圜-4-甲胺 置換嗎福琳’獲得2-丁基-3-(4-{[(2,2-二甲基-1，3-二氧伍圜-4-基） 甲基]胺基}苯基）喳唑啉-4(3H)-酮（33%)，為無色固體：熔點 148-150°C ; iHNMR (300 MHz，CDC13) 6 8.26 (dd，J = 8.1，0.9 Hz，1H)， 7.79-7.68 (m，2H)，7.49-7.41 (m，1H)，7.06-6.98 (m，2H)，6.78-6.70 (m， 2H)，4.48-4.34 (m，1H)，4.14 (dd，J = 8.1，6·3 Hz, 1H)，3·81 (dd，J = 8.1， 6.3 Hz，1H)，3.42-3.18 (m，2H)，2.61-2.41 (m，2H)，1.73-1.59 (m，2H)， / 1.35-1.21 (m，2H)，0.83 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 6 163.0，158.5，148.6，134.5，129.1，127.2，126.9，126.5，120.9，113.7, 113.6, 109.8, 74.5, 67.3, 46.7, 35.7, 29.5, 27_1，25.4, 22.5, 13.9 ; MS (ES+) m/z 408.2 (M + 1). 實例95 2-丁基-3-{4-[(2,3-二羥基丙基）胺基]苯基}喹唑啉_4(3H)-_之合成Inconsistent changes were made according to the procedure described in Example 86, replacing 128409 -217-200836743 with 3-(4-bromophenyl)-2-butylquinazolin-4(3H)-one 3- (4-bromo-2-chlorophenyl)-2-butyl^ quinalin-4(3H)-one, and 2,2-dimethyl-1,3-dioxolan-4-e Amine substitution of whallin' to obtain 2-butyl-3-(4-{[(2,2-dimethyl-1,3-dioxoindol-4-yl)methyl]amino}phenyl) Oxazoline-4(3H)-one (33%) as colorless solid: mp 148-150°C; iHNMR (300 MHz, CDC13) 6 8.26 (dd, J = 8.1, 0.9 Hz, 1H), 7.79- 7.68 (m, 2H), 7.49-7.41 (m, 1H), 7.06-6.98 (m, 2H), 6.78-6.70 (m, 2H), 4.48-4.34 (m, 1H), 4.14 (dd, J = 8.1 ,6·3 Hz, 1H),3·81 (dd, J = 8.1, 6.3 Hz, 1H), 3.42-3.18 (m, 2H), 2.61-2.41 (m, 2H), 1.73-1.59 (m, 2H ), / 1.35-1.21 (m, 2H), 0.83 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 6 163.0, 158.5, 148.6, 134.5, 129.1, 127.2, 126.9, 126.5, 120.9, 113.7, 113.6, 109.8, 74.5, 67.3, 46.7, 35.7, 29.5, 27_1, 25.4, 22.5, 13.9; MS (ES+) m/z 408.2 (M + 1). Example 95 Synthesis of 2-butyl-3-{4-[(2,3-dihydroxypropyl)amino]phenyl}quinazoline-4(3H)-_

將2-丁基-3-(4-{[(2,2-二甲基-1，3-二氧伍圜-4-基）甲基]胺基} 苯基 &gt;奎唾啉-4(3H)-酮（0.04克，0.098毫莫耳）在醋酸（80%，10 毫升）中之溶液於環境溫度下攪拌十六小時。使反應混合物 在真空中濃縮至乾涸，使殘留物接受管柱層析（醋酸乙酯）， 獲得2-丁基-3-{4-[(2,3-二羥基丙基）胺基]苯基}喹唑啉4(3H)-酮’為無色固體（〇_〇19 克，53%):容點 i〇8-ll〇°C ; iHNMRpOO MHz，CDC13) 5 8.28-8.21 (m，1H)，7.80-7.68 (m，2H)，7.49-7.41 (m，1H)， 128409 -218- 200836743 7·04·6·95 (m，2H)，6.78-6.68 (m，2H)，3.99-3.88 (m，1H)，3.78-3.56 (m， 2H)，3.35-3.12 (m，2H)，3.25-2.70 (br5 2H)，2.50 (t，J = 7.8 Hz，2H)， 1.72-1.60 (m，2H)，1.34-1.20 (m，2H)，0.82 (t，J = 7·5 Hz，3H) ; MS (ES+) m/z 368.2 (M + 1). 實例96 2_丁基-3-{4-[(2-經基-3-苯氧基丙基）胺基]苯基卜奎唑啉-4(3H)- 酮之合成2-butyl-3-(4-{[(2,2-dimethyl-1,3-dioxoindol-4-yl)methyl]amino}phenyl] quinolate-4 A solution of (3H)-one (0.04 g, 0.098 mmol) in acetic acid (80%, 10 mL) was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo to dryness Column chromatography (ethyl acetate) to give 2-butyl-3-{4-[(2,3-dihydroxypropyl)amino]phenyl}quinazoline 4(3H)-one' as a colorless solid (〇_〇19 g, 53%): tolerance point i〇8-ll〇°C; iHNMRpOO MHz, CDC13) 5 8.28-8.21 (m,1H), 7.80-7.68 (m,2H), 7.49-7.41 ( m,1H), 128409 -218- 200836743 7·04·6·95 (m,2H), 6.78-6.68 (m,2H),3.99-3.88 (m,1H),3.78-3.56 (m, 2H), 3.35-3.12 (m, 2H), 3.25-2.70 (br5 2H), 2.50 (t, J = 7.8 Hz, 2H), 1.72-1.60 (m, 2H), 1.34-1.20 (m, 2H), 0.82 (t , J = 7·5 Hz, 3H); MS (ES+) m/z 368.2 (M + 1). Example 96 2 -butyl-3-{4-[(2-amino-3-phenoxypropyl) Synthesis of aryl]phenyl brepazoline-4(3H)-one

使3-(4-胺基苯基&gt;2-丁基喹唑啉-4(3H)-酮（0.147克，0.50毫莫 耳）與1，2-環氧基-3-苯氧基丙烷（0.068毫升，0.50毫莫耳）之混 合物在異丙醇（5毫升）中回流三小時。使反應混合物在真空 中濃縮至乾涸，使殘留物接受管柱層析（醋酸乙酯/己烷/異 丙醇，4/6/0.25)，獲得2-丁基-3-{4-[(2-經基-3·苯氧基丙基）胺基] 苯基卜奎唑啉-4(3H)-S同，為無色固體（0.150克，68%):熔點89-91 °C ； NMR (300 MHz? CDC13) δ 8.26 (d? J = 7.8 Hz5 1H)9 7.80-7.68 (m，2H)，7.49-7.40 (m，1H)，7.35-7.24 (m，2H)，7.05-6.88 (m5 5H)，6.76 (d， J = 8·7 Hz，2H)，4.34-4.23 (m，1H)，4.14-4.03 (m，2H)，3.53-3.29 (m，2H)， 2.78-2.60 (br，1H)，2.51 (t，J = 7.8 Hz，2H)，1.74-1.57 (m，2H)，1.34-1.20 (m，2H)，0.83 (t，J = 7.5 Hz，3H) ; 13 C NMR (75 MHz，CDC13) δ 163.2, 158.5, 148.8, 147.5, 134.5, 129.7, 129.0, 127·2, 126.9, 126.8, 126.6, 121.5, 120.8, 114.6, 113.8，113.7, 70.0, 68.8, 46.6, 35.7, 29·5, 22.5, 13.9 ; MS 128409 -219- 200836743 (ES+) m/z 444.2 (Μ + 1). 實例97 [4-(2-丁基-4-酮基喹唑啉-3(4H)-基）環己基]胺基甲酸第三丁酯 之合成3-(4-Aminophenyl)2-butylquinazolin-4(3H)-one (0.147 g, 0.50 mmol) and 1,2-epoxy-3-phenoxypropane A mixture of (0.068 mL, 0.50 mmol) was refluxed in isopropyl alcohol (5 mL) for three hours. The reaction mixture was concentrated to dryness in vacuo. Isopropanol, 4/6/0.25), 2-butyl-3-{4-[(2-amino-3-phenoxypropyl)amino]phenyl brepazoline-4 (3H) -S, as a colorless solid (0.150 g, 68%): mp 89-91 ° C; NMR (300 MHz? CDC13) δ 8.26 (d? J = 7.8 Hz5 1H)9 7.80-7.68 (m, 2H) , 7.49-7.40 (m, 1H), 7.35-7.24 (m, 2H), 7.05-6.88 (m5 5H), 6.76 (d, J = 8·7 Hz, 2H), 4.34 - 4.23 (m, 1H), 4.14-4.03 (m, 2H), 3.53-3.29 (m, 2H), 2.78-2.60 (br, 1H), 2.51 (t, J = 7.8 Hz, 2H), 1.74-1.57 (m, 2H), 1.34 1.20 (m, 2H), 0.83 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) δ 163.2, 158.5, 148.8, 147.5, 134.5, 129.7, 129.0, 127·2, 126.9, 126.8 , 126.6, 121.5, 120.8, 114.6, 113.8, 113.7, 70.0, 68.8, 46.6, 35.7, 29·5, 22.5, 13.9 ; MS 128409 -219- 200836743 (ES+) m/z 444.2 (Μ + 1). Example 97 [4-(2-butyl-4-ketoquinazoline-3(4H) Synthesis of -butyl]cyclohexyl]amino carboxylic acid tert-butyl ester

於（4-{[(2-胺基苯基）幾基]胺基}環己基）胺基甲酸第三-丁酯 (0.10克，0.30毫莫耳）在DMF (10毫升）中之溶液内，在環境 溫度下，添加原戊酸三甲酯（0.18毫升，1毫莫耳）與醋酸（〇.5 毫升）。將反應混合物於120°C下攪拌四天，並倒入水（30毫 升）中。以醋酸乙酯（3 X 50毫升）萃取此懸浮液。將合併之有 機層以飽和碳酸鈉溶液與水洗滌，以無水硫酸鈉脫水乾 燥，及過濾。使濾液在真空中濃縮至乾涸。使殘留物接受 管柱層析（在己烷中之30%醋酸乙酯），獲得[4_(2· 丁基-4-酮基 4：唾啉-3(4H)-基）環己基]胺基甲酸第三-丁酯（〇 〇63克，53%)， 為無色固體：1H NMR (300 MHz，CDC13) (5 8.19 (d，J = 7.8 Hz，1H)， 7.75-7.55 (m，2H)，7·41 (dd，J = 7.8, 7·5 Hz，1H)，4.51-0.80 (m，28H); MS (ES+) m/z 400.2 (M + 1). 實例98 3-(4-胺基環己基）-2-丁基喹唑啉-4(3H).鹽酸鹽之合成To a solution of (4-{[(2-aminophenyl))]amino}cyclohexyl)carbamic acid tert-butyl ester (0.10 g, 0.30 mmol) in DMF (10 mL) Add trimethyl ortho-valerate (0.18 ml, 1 mmol) to acetic acid (〇. 5 mL) at ambient temperature. The reaction mixture was stirred at 120 ° C for four days and poured into water (30 mL). The suspension was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with saturated sodium carbonate solution and water, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (30% ethyl acetate in hexane) to give [4-(2-butyl-4-keto-4: s. s. Tri-butyl carboxylic acid (〇〇 63 g, 53%), as colorless solid: 1H NMR (300 MHz, CDC13) (5 8.19 (d, J = 7.8 Hz, 1H), 7.75-7.55 (m, 2H ), 7·41 (dd, J = 7.8, 7·5 Hz, 1H), 4.51-0.80 (m, 28H); MS (ES+) m/z 400.2 (M + 1). Example 98 3-(4- Synthesis of Aminocyclohexyl)-2-butylquinazoline-4(3H). Hydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用[4-(2-丁基-4-酮基喹唑啉_3 (4ίί)基）環己基]胺基甲酸第三_丁 128409 -220- 200836743 酯置換[2-(2-丁基-4-酮基喳唑啉-3(4H)-基）乙基]胺基甲酸第三-丁酯，獲得3-(4-胺基環己基）-2-丁基喹唑啉-4(3H)-酮鹽酸鹽 (39%)，為無色固體：1H NMR (300 MHz，CD3 OD) 5 8.24 (d，J = 7.8 Hz，lH)，7.99-7.89 (m，lH)，7.76-7.61(m，2H)，4.384.18(m，lH),3.31-2.79 (m，5H)，2.29-1.48 (m, 12H)，1.07 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz，CD3OD) 5 161.9, 137.1，129.6, 128·3, 122·2, 121.6, 61.0, 50.3, 35.2, 31·0, 30·8, 29.6, 27·1，23·5, 14.1 ; MS (ES+) m/z 300.2 (Μ + 1). 實例99 4-(2-丁基同基ρ奎σ坐琳-3(4Η)-基）六氫ρ比咬-1-叛酸第三-丁酉旨 之合成According to the procedure as described in Example 74, an irrelevant change was carried out using [4-(2-butyl-4-ketoquinazolin-3-3 (4ίί))cyclohexyl]carbamic acid as the third 128409 -220-200836743 Ester-substituted [2-(2-butyl-4-ketooxazoline-3(4H)-yl)ethyl]carbamic acid tert-butyl ester to give 3-(4-amine Cyclohexyl)-2-butylquinazoline-4(3H)-one hydrochloride (39%) as colorless solid: 1H NMR (300 MHz, CD3 OD) 5 8.24 (d, J = 7.8 Hz, lH), 7.99-7.89 (m, lH), 7.76-7.61 (m, 2H), 4.384.18 (m, lH), 3.31-2.79 (m, 5H), 2.29-1.48 (m, 12H), 1.07 ( t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CD3OD) 5 161.9, 137.1, 129.6, 128·3, 122·2, 121.6, 61.0, 50.3, 35.2, 31·0, 30· 8, 29.6, 27·1,23·5, 14.1 ; MS (ES+) m/z 300.2 (Μ + 1). Example 99 4-(2-butyl-iso-group ρ 奎 坐 sits -3 (4Η)- Base) hexahydro ρ ratio bite-1-retribution acid third-butan

按照如實例97中所述之程序，施行無關緊要之改變，使 用4-{[(2-胺基苯基）幾基]胺基}六氫吡啶_丨_羧酸第三_丁酯置 換(4-{[(2-胺基苯基）幾基]胺基μ袠己基）胺基甲酸第三_丁酯， 獲得4-(2-丁基-4-酮基喳唑啉_3(4Η)-基）六氫吡啶小羧酸第三_ 丁醋（90%) ’ 為無色固體：1 η NMR C300 MHz，CDC13) 5 &amp;17 (d，J =7.8 Hz，1H)，7·73-7·58 (m，2H)，7.45-7.37 (m，1H)，4.51-0.80 (m，27H); MS (ES+) m/z 386.2 (M + 1). 實例100 2-丁基-3-六氫吡啶_4-基喳唑啉_4(3H)•酮二鹽酸鹽之合成According to the procedure as described in Example 97, an insignificant change was made using a 4-{[(2-aminophenyl)methyl]amino}hexahydropyridine-indole-carboxylic acid tert-butyl ester ( 4-{[(2-Aminophenyl)methyl]aminopyrylhexyl)carbamic acid tert-butyl ester, 4-(2-butyl-4-ketooxazoline_3 (4Η) )-yl)hexahydropyridine small carboxylic acid third _ vinegar (90%) ' is a colorless solid: 1 η NMR C300 MHz, CDC13) 5 &amp; 17 (d, J = 7.8 Hz, 1H), 7.73 -7·58 (m, 2H), 7.45-7.37 (m, 1H), 4.51 - 0.80 (m, 27H); MS (ES+) m/z 386.2 (M + 1). Example 100 2-butyl-3 Synthesis of hexahydropyridine_4-yloxazoline-4(3H)•one dihydrochloride

按照如實例74中所述之程序 施行無關緊要之改變，使 128409 -221 - 200836743 用4-(2-丁基·4_酮基喹唑啉_3(4H)_基）六氫吡啶小羧酸第'一 酯置換[2-(2•丁基-4-酮基喳唑啉-3(4H)-基）乙基]胺基甲酸第二 丁酯，獲得2·丁基-3·六氫吡啶斗基喹唑啉-4(3H)__二鹽酸璧 (88%)，為無色固體·· MS (ES+) m/z 286.2 (M + 1). 實例101 2-丁基各[1-(2-羥基-3-苯氧基丙基）六氫吡啶_4_基]喳唑啉 •4(3H)_酮之合成An insignificant change was made according to the procedure described in Example 74, using 4-(2-butyl-4-ketoquinazoline-3(4H)-yl)hexahydropyridine carboxycarboxylate for 128409-221 - 200836743 Replacement of the second ester of [2-(2•butyl-4-ketooxazoline-3(4H)-yl)ethyl]carbamic acid with the acid ''-ester to obtain 2·butyl-3·6 Hydrogen pyridinyl quinazolin-4(3H)_-dihydroguanidine hydrochloride (88%) as a colorless solid · MS (ES+) m/z 286.2 (M + 1). Example 101 2-butyl each [1 Synthesis of -(2-hydroxy-3-phenoxypropyl)hexahydropyridine-4-yl]oxazoline•4(3H)-one

按照如實例96中所述之程序，施行無關緊要之改變，使 用2-丁基-3-六氫吡啶-4-基喳唑啉-4(3H&gt;酮置換3-(4-胺基苯 基&gt;2-丁基喹唑啉-4(3H)-酮，獲得2-丁基-3-〇(2·經基-3-苯氧基 丙基）六IL p比唆-4-基]π奎唾啦-4(3Η)-ϊ同（56%)，為無色固體：溶 fInconsistent changes were made according to the procedure described in Example 96 using 2-butyl-3-hexahydropyridin-4-yloxazoline-4 (3H&gt; ketone to replace 3-(4-aminophenyl) &gt; 2-butylquinazoline-4(3H)-one to give 2-butyl-3-indole (2. carbyl-3-phenoxypropyl) hexa-Ip-p--4-yl] π奎唾拉-4(3Η)-ϊ同(56%), is a colorless solid: soluble f

點 120-122°C ; 4 NMR (300 MHz，CDC13) 5 8.23-8.16 (m，1Η)， 7.74-7.65 (m，1H)，7.59 (d，J = 7.8 Hz，1H)，7.47-7.23 (m，3H)，7.02-6.88 (m，3H)，4.22-3.95 (m，4H)，3.35-3.00 (m，4H)，2_87 (t，J = 7·8 Hz，2H)， 2.65 (d，J = 6.6 Hz，2H)，2.46 (t，J = 10.8 Hz，1H)，2.21 (t，J = 10.8 Hz， 1H)，1.85-1.63 (m，4H)，1·59·1·45 (m，2H)，1.25 (s，1H)，1.01 (t，J = 7.5 Hz， 3H) ; 13C NMR (75 MHz，CDC13) 6 163.0, 158.8, 157.2, 147.0, 134.3, 129.6，126.7，126.61，126.58，121.1，114.7, 70.2, 65.9, 60.2, 55.3, 52.9, 36.5, 30.1，28.1，27.9, 22.7, 14.1 ; MS (ES+) m/z 436.2 (M + 1)· 實例102 3-{l-[3-(苄氧基）-2-羥丙基]六氫吡啶-4-基}-2-丁基喹唑啉-4(3H)- 128409 -222 - 200836743 酮之合成Point 120-122 ° C; 4 NMR (300 MHz, CDC13) 5 8.23-8.16 (m, 1 Η), 7.74-7.65 (m, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.47-7.23 ( m, 3H), 7.02-6.88 (m, 3H), 4.22-3.95 (m, 4H), 3.35-3.00 (m, 4H), 2_87 (t, J = 7·8 Hz, 2H), 2.65 (d, J = 6.6 Hz, 2H), 2.46 (t, J = 10.8 Hz, 1H), 2.21 (t, J = 10.8 Hz, 1H), 1.85-1.63 (m, 4H), 1·59·1·45 (m , 2H), 1.25 (s, 1H), 1.01 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) 6 163.0, 158.8, 157.2, 147.0, 134.3, 129.6, 126.7, 126.61, 126.58, 121.1, 114.7, 70.2, 65.9, 60.2, 55.3, 52.9, 36.5, 30.1, 28.1, 27.9, 22.7, 14.1; MS (ES+) m/z 436.2 (M + 1)· Example 102 3-{l-[3- (Benzyloxy)-2-hydroxypropyl]hexahydropyridin-4-yl}-2-butylquinazoline-4(3H)-128409 -222 - 200836743 Synthesis of ketone

按照如實例98中所述之程序，施行無關緊要之改變，使 用2-丁基-3-六氫吡啶-4-基喳唑啉-4(3H)-酮置換3-(4-胺基苯 基）-2-丁基喳唑啉-4(3H)-_，及苄基縮水甘油基醚置換1，2-環 氧基-3-苯氧基丙烷，獲得3-{1-[3-(芊氧基）_2_經丙基]六氫吡啶 -4-基}-2-丁基喹唑啉-4(3H)-酮（64%)，為無色固體：1 H NMR (300 MHz，CDC13) 5 8.05 (dd，J = 8.1，0·9 Ηζ，1Η)，7·59-7·49 (m，1Η)，7·44 (d， J = 8·1 Ηζ，1Η)，7.31-7.08 (m，6Η)，4·44 (s，2Η)，3-0-4.07 (br，1Η)，3.843.72 (m，1H)，3.44-3.32 (m，2H)，3.13-2.80 (m，5H)，2.71 (t，J = 7.8 Hz，2H)， 2·43-2·15 (m，3H)，2.03-1.90 (m，1H)，1.71-1.27 (m，6H)，0.86 (t，J = 7.5 Hz，3H); 13C NMR (75 MHz，CDC13)占 162.9, 157.2, 147.0, 138.2, 134.1， 128.5, 127.8, 127.7, 126.6, 126.5, 126.4, 121.8, 73.6, 72.6, 66.6, 60.3, 55.3, 52.8，36.4，30.0，28.2，28.0，22.6，14.0 ; MS (ES+) m/z 450.2 (M + 1). 實例103Inconsistent changes were made using 2-butyl-3-hexahydropyridin-4-yloxazoline-4(3H)-one to replace 3-(4-aminobenzene) according to the procedure described in Example 98. ))-2-butyloxazoline-4(3H)--, and benzyl glycidyl ether to replace 1,2-epoxy-3-phenoxypropane to obtain 3-{1-[3- (Methoxy)_2_propyl)hexahydropyridin-4-yl}-2-butylquinazoline-4(3H)-one (64%) as colorless solid: 1 H NMR (300 MHz, CDC13) 5 8.05 (dd, J = 8.1, 0·9 Ηζ, 1Η), 7·59-7·49 (m, 1Η), 7·44 (d, J = 8·1 Ηζ, 1Η), 7.31 7.08 (m,6Η),4·44 (s,2Η),3-0-4.07 (br,1Η),3.843.72 (m,1H),3.44-3.32 (m,2H),3.13-2.80 (m , 5H), 2.71 (t, J = 7.8 Hz, 2H), 2·43-2·15 (m, 3H), 2.03-1.90 (m, 1H), 1.71-1.27 (m, 6H), 0.86 (t , J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) accounted for 162.9, 157.2, 147.0, 138.2, 134.1, 128.5, 127.8, 127.7, 126.6, 126.5, 126.4, 121.8, 73.6, 72.6, 66.6, 60.3, 55.3, 52.8, 36.4, 30.0, 28.2, 28.0, 22.6, 14.0; MS (ES+) m/z 450.2 (M + 1). Example 103

N-[4-(2-丁基-4-_基喹也啉-3(4H)-基）苯基]甲烷磺醯胺之合成 於3-(4-胺基苯基)-2-丁基喳唑啉_4(3办酮（〇·2〇〇克，〇⑽毫莫 耳）在二氣甲烷（5.0毫升）中之溶液内，在〇。〇下，添加三乙 胺（0·114耄升，0.819毫莫耳）與氯化甲烷磺醯（〇 〇64毫升，〇.819 毫莫耳）。將所形成之混合物於環境溫度下攪拌十六小時， 128409 -223 . 200836743Synthesis of N-[4-(2-butyl-4-ylquinoxaline-3(4H)-yl)phenyl]methanesulfonamide in 3-(4-aminophenyl)-2-butene In the solution of oxazolidine _4 (3 ketone (〇·2〇〇g, 〇(10) mmol) in di-methane (5.0 ml), under tritium, add triethylamine (0· 114 liters, 0.819 millimoles) with methane chloride sulfonium chloride (〇〇 64 ml, 〇.819 mmol). The resulting mixture was stirred at ambient temperature for 16 hours, 128409 -223 . 200836743

並添加二氯甲烧（100毫升）。以水及鹽水洗滌混合物。將有 機層以無水硫酸鈉脫水乾燥，及過濾。使濾液在真空中濃 縮至乾涸。使殘留物接受管柱層析（在己烷中之35%醋酸乙 酯），獲得N-[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]甲烷磺醯 胺（0.060 克，24%)，為無色固體：熔點 176-178°c ; ihnmr(300 MHz，CDC13) 3 8.28 (d，J = 7.8 Hz，1H)，7.83-7.69 (m，2H)，7.48 (t，J = 7·8 Hz，1H)，7.41-7.17 (m，5H)，3.08 (s，3H)，2·45 (t，J = 7·8 Hz, 2H)，1.68 (五重峰，J = 7.5 Hz，2H)，1.35-1.19 (m，2H)，0.81 (t5 J = 7·5 Hz，3H); 13C NMR (75 MHz, CDC13) 5 163.2, 157.1，147.6, 138.3, 135.0, 133.6, 129.7, 127.2, 127.17, 127.0, 121.2, 120.5, 39.9, 35.6, 29.3, 22.4, 13.8 ; MS (ES+) m/z 372.1 (M + 1). 實例104 N-[4-(2-丁基-4·酮基喳唑淋_3(姐)_基）苯基]乙醯胺之合成Add methylene chloride (100 ml). The mixture was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo. The residue was subjected to column chromatography (35% ethyl acetate in hexane) to afford N-[4-(2-butyl-4-ketooxazolyl-3(4H)-yl)phenyl. Methanesulfonamide (0.060 g, 24%) as a colorless solid: m.p. 176-178.c; ihnmr (300 MHz, CDC13) 3 8.28 (d, J = 7.8 Hz, 1H), 7.83-7.69 (m, 2H), 7.48 (t, J = 7·8 Hz, 1H), 7.41-7.17 (m, 5H), 3.08 (s, 3H), 2·45 (t, J = 7·8 Hz, 2H), 1.68 (five peaks, J = 7.5 Hz, 2H), 1.35-1.19 (m, 2H), 0.81 (t5 J = 7·5 Hz, 3H); 13C NMR (75 MHz, CDC13) 5 163.2, 157.1, 147.6, 138.3, 135.0, 133.6, 129.7, 127.2, 127.17, 127.0, 121.2, 120.5, 39.9, 35.6, 29.3, 22.4, 13.8; MS (ES+) m/z 372.1 (M + 1). Example 104 N-[4-( Synthesis of 2-butyl-4·ketocarbazole _3(sister)_yl)phenyl]acetamide

於3-(4-胺基苯基）-2-丁基4 σ坐p林·4(3Η)-_ (0.200克，0.683毫莫 耳）在二氣甲烷（5.0毫升）中之溶液内，在〇。〇下，添加三乙 胺（0.114毫升0.819毫莫耳）與氯化乙醯（0·058毫升，〇 819毫莫 耳）。將所形成之混合物於環境溫度下攪拌十六小時，並添 加二氯甲烷（100毫升）。以水及鹽水洗滌混合物。將有機層 以無水硫酸鈉脫水乾燥，及過濾。使濾液在真空中濃縮至 乾酒。使殘留物接受管柱層析（在己烷中之35〇/〇醋酸乙酯）， 獲得Ν-[4·(2-丁基-4-酮基喹唑啉-3(4Η&gt;基）苯基]乙醯胺（〇·2〇〇 128409 -224- 200836743 克，87%)，為無色固體：熔點 2〇6-2〇8t： ; 1H NMR (300 MHz, CDC13) (5 8.64-8.53 (br，1H)，8.24 (d，J = 7·8 Hz，1H)，7.84-7.71 (m，2H)， 7.58-7.44 (m，3H)，7.09 (d，J = 8.7 Hz，2H)，2.43 (t，J = 7·8 Hz，2H)，2.09 (s，3H)，1.66 (五重峰，j = 7·5 Hz，2H)，1.31-1.17 (m，2H)，0-81 (t，J = 7.5 Hz，3H); 13C NMR (75 MHz，CDC13) δ 169.2, 163.5, 157.5, 147.8, 139.5, 135.0，132.1，128.3，127.4，126.9，126.8，121.4，120·5, 35.6, 29.3, 24.4, 22.4, 13·9 ; MS (ES+) m/z 337.2 (Μ + 1). 2-丁基-3_[4-〇比啶基胺基）苯基p奎唑啉4(3H)_酮之合成 實例105In a solution of 3-(4-aminophenyl)-2-butyl 4 σ p 林 · 4(3Η)-_ (0.200 g, 0.683 mmol) in di-methane (5.0 mL) Here. Under the arm, triethylamine (0.114 ml 0.819 mmol) was added with ethyl acetate (0·058 ml, 819 819 mmol). The resulting mixture was stirred at ambient temperature for sixteen hours and dichloromethane (100 mL) was evaporated. The mixture was washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dry wine. The residue was subjected to column chromatography (35 〇 / 〇 ethyl acetate in hexane) to give Ν-[4·(2-butyl-4-ketoquinazoline-3(4Η&gt; yl)benzene Ethylamine (〇·2〇〇128409 -224- 200836743 g, 87%), as colorless solid: melting point 2〇6-2〇8t: ; 1H NMR (300 MHz, CDC13) (5 8.64-8.53 ( Br,1H), 8.24 (d, J = 7·8 Hz, 1H), 7.84-7.71 (m, 2H), 7.58-7.44 (m, 3H), 7.09 (d, J = 8.7 Hz, 2H), 2.43 (t, J = 7·8 Hz, 2H), 2.09 (s, 3H), 1.66 (five peaks, j = 7·5 Hz, 2H), 1.31-1.17 (m, 2H), 0-81 (t , J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 169.2, 163.5, 157.5, 147.8, 139.5, 135.0, 132.1, 128.3, 127.4, 126.9, 126.8, 121.4, 120·5, 35.6, 29.3, 24.4, 22.4, 13·9 ; MS (ES+) m/z 337.2 (Μ + 1). 2-butyl-3_[4-indolylamino)phenyl p-quinazoline 4(3H)-one Synthesis example 105

按照如實例87中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）-2-丁基喳唑啉·4(3Η)_酮置換3-(4-溴基-2-氯苯 基）-2-丁基4唑啉-4(3H)，，及2-胺基^比啶置換嗎福啉，獲得 2_丁基-H4七比啶_2_基胺基）苯基]4唑啉_4(3H)-酮（5〇°/〇)，為無 色固體：4 NMR (300 MHz，CDC13) 5 8.28 (dd，J = 8.1，1.2 Hz，1H)， 8.22 (dd，J = 5.1，1·2 Hz，1H)，7.79-7.68 (m，2H)，7.59-7.42 (m，4H)，7.24 (s，1H)，7.12 (d，J = 8.7 Hz，1H)，6.82 (d，J = 8.4 Hz，1H)，6.75 (dd，J = 6.6, 5.0 Hz，1H)，2.47 (t，J = 7.8 Hz，2H)，1.67 (五重峰，J = 7·5 Hz，2H)， 1.33-U8 (m，2H)，0.81 (t，J = 7·2 Hz，3H) ; 13 C NMR (75 MHz，CDC13) 5 163.0，157.8，155.2，147.9，147.6，141.7，137.7，134.5，130.4, 128.8, 127.0, 126·5, 120.7, 119.7, 115.5, 109.9, 35.6, 29.3, 23.4, 13·8 ; MS (ES+) m/z 371.0 (M + 1). 128409 -225 - 200836743 實例106 2_丁基-3-(4-嗎福啉斗基苯基）喹唑啉_4(3H)__之合成Inconsistent changes were made according to the procedure described in Example 87, using 3-(4-bromophenyl)-2-butyloxazoline·4(3Η)-one to replace 3-(4-bromo-) 2-Chlorophenyl)-2-butyl-4-oxazoline-4 (3H), and 2-aminopyridinyl substituted morphine to obtain 2-butyl-H4 heptaidine-2-aminol Phenyl] 4 oxazoline _4(3H)-one (5 〇 ° / 〇) as a colorless solid: 4 NMR (300 MHz, CDC13) 5 8.28 (dd, J = 8.1, 1.2 Hz, 1H), 8.22 (dd, J = 5.1,1·2 Hz, 1H), 7.79-7.68 (m, 2H), 7.59-7.42 (m, 4H), 7.24 (s, 1H), 7.12 (d, J = 8.7 Hz, 1H ), 6.82 (d, J = 8.4 Hz, 1H), 6.75 (dd, J = 6.6, 5.0 Hz, 1H), 2.47 (t, J = 7.8 Hz, 2H), 1.67 (five peaks, J = 7·) 5 Hz, 2H), 1.33-U8 (m, 2H), 0.81 (t, J = 7·2 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 163.0, 157.8, 155.2, 147.9, 147.6, 141.7 , 137.7, 134.5, 130.4, 128.8, 127.0, 126·5, 120.7, 119.7, 115.5, 109.9, 35.6, 29.3, 23.4, 13·8 ; MS (ES+) m/z 371.0 (M + 1). 128409 -225 - 200836743 Example 106 Synthesis of 2_Butyl-3-(4-fosfolininylphenyl)quinazoline_4(3H)__

按照如貫例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基&gt;2-丁基喹唑啉-4(3H&gt;酮置換3_(4-溴基_2_氯苯 基）-2-丁基喹唑啉-4(3H)__，獲得丁基！&amp;嗎福啉斗基苯基） 峻坐琳-4(3H)’（59%) ’為無色固體：熔點154_156。〇 ; 1hnmr (300 MHz, CDC13) 5 8.24 (dd? J = 8.1, 0.9 Hz, 1H)? 7.77-7.66 (m? 2H)? 7.43 (td，J - 7.8, 1.5 Hz，1H)，7.12 (d，J = 8.7 Hz，2H)，7.01 (d，J = 8.7 Hz， 2H)? 3.88 (t? J = 4.8 Hz? 4H)? 2.23 (t, J = 4.8 Hz, 4H)5 2.46 (t? J - 7.8 Hz5 2H)，1.65 (五重峰，j = 7 8 Hz，2H)，】％ (六重峰，了 = 7 8 Hz，2h)， 〇·80 (t，J = 75 HZ，3H) ; &quot;C NMR (75 MHz，CDC13) 5 162.8, 151.5, 134.4, 128_9, 128.7, 127.0, 126.9, 126.4, 120.7, 116.0, 66.8, 48.8, 35.6, 29.3? 22.4? 13.8 ； MS (ES+) m/z 364.0 (M + 1). 實例107 3_{[4-(2-丁基4,基峻σ坐啉_3(4H)-基）苯基]胺基丨四氫吡咯小 羧酸第三-丁醋之合成 128409According to the procedure described in Example 86, irrelevant changes were made using 3-(4-bromophenyl) 2-butylquinazoline-4 (3H&gt; ketone to replace 3_(4-bromo-2) _Chlorophenyl)-2-butylquinazoline-4(3H)__, obtained butyl! & florin phenyl phenyl) sylvestre-4(3H)' (59%) 'is colorless Solid: melting point 154_156. 〇; 1hnmr (300 MHz, CDC13) 5 8.24 (dd? J = 8.1, 0.9 Hz, 1H)? 7.77-7.66 (m? 2H)? 7.43 (td, J - 7.8, 1.5 Hz, 1H ), 7.12 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H)? 3.88 (t? J = 4.8 Hz? 4H)? 2.23 (t, J = 4.8 Hz, 4H)5 2.46 (t? J - 7.8 Hz5 2H), 1.65 (five peaks, j = 7 8 Hz, 2H), ]% (six peaks, = 7 8 Hz, 2h), 〇·80 (t, J = 75 HZ,3H) ; &quot;C NMR (75 MHz, CDC13) 5 162.8, 151.5, 134.4, 128_9, 128.7, 127.0, 126.9, 126.4, 120.7, 116.0, 66.8, 48.8, 35.6, 29.3? 22.4? 13.8 ; MS (ES+) m/z 364.0 (M + 1). Example 107 3_{[4-(2-butyl 4, thiophene syl- s-(3H)-yl)phenyl]aminoindole tetrahydropyrrole Synthesis of carboxylic acid third-butyl vinegar 128409

按肤如貫例86中所述之程序，施行無關緊要之改變，使 用3_(4-溴笨基）_2_丁基喳唑啉_4(3印_酮置換…溴基冬氯苯 基）2 丁基p奎唾啉_4(扭)_酮，及胺基四氫吡咯·ι_羧酸第三_ -226- 200836743 丁酯置換嗎福#，獲得3-{[4-(2-丁基-4-酮基p奎唾琳-3(4H)-基） 苯基]胺基}四氫吡咯-1-羧酸第三-丁 S旨（46%)，為無色固體： 熔點 184-186。(： ； iH NMR (300 MHz，CDC13) (5 8.25 (d，J = 7.8 Hz, 1H)，7.76-7.65 (m，2H)，7.43 (t，J = 7.8 Hz，1H)，7.02 (d，J = 8·7 Hz，2H)， 6.69 (d5 J = 8·7 Hz，2H)，4.13-3.94 (m，2H)，3.79-3.66 (m，1H)，3.55-3.40 (m，2H)，3·36-3·20 (m，1H)，2.49 (t，J = 6.6 Hz，2H)，2.28-2.17 (m，1H)， 2.00-1.86 (m，1H)，1.72-1.58 (m，2H)，1.33-U9 (m，2H)，0.81 (t，J = 7.2 Hz，3H); 13CNMR (75 MHz，CDC13) 5 163.0, 158.2, 154.6, 147.5, 147.3, 134.3, 129.0, 127.0, 126.8, 126.4, 120.8, 79.6, 52.0, 43.8, 35.6, 29.4, 28·5, 22.4, 13.8 ； MS (ES+) m/z 463.1 (M + 1). 實例108 2-丁基-3-(4_{[2-(二甲胺基）乙基]胺基}苯基 &gt;奎唑啉_4(3H)·酮之 合成According to the procedure described in Example 86, irrelevant changes were made using 3_(4-bromo-phenyl)-2-butyloxazoline-4 (3 - ketone-substituted ... bromo-homochlorophenyl) 2 butyl p-quinoline _4 (twist) ketone, and amine tetrahydropyrrole · ι_carboxylic acid third _ -226- 200836743 butyl ester replacement ahfu #, obtain 3-{[4-(2- Butyl-4-keto p-quineline-3(4H)-yl)phenyl]amino}tetrahydropyrrole-1-carboxylic acid tert-butyr (46%) as colorless solid: mp 184 -186. (: ; iH NMR (300 MHz, CDC13) (5 8.25 (d, J = 7.8 Hz, 1H), 7.76-7.65 (m, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8·7 Hz, 2H), 6.69 (d5 J = 8·7 Hz, 2H), 4.13-3.94 (m, 2H), 3.79-3.66 (m, 1H), 3.55-3.40 (m, 2H), 3·36-3·20 (m,1H), 2.49 (t, J = 6.6 Hz, 2H), 2.28-2.17 (m, 1H), 2.00-1.86 (m, 1H), 1.72-1.58 (m, 2H) ),1.33-U9 (m,2H), 0.81 (t, J = 7.2 Hz, 3H); 13CNMR (75 MHz, CDC13) 5 163.0, 158.2, 154.6, 147.5, 147.3, 134.3, 129.0, 127.0, 126.8, 126.4 , 120.8, 79.6, 52.0, 43.8, 35.6, 29.4, 28·5, 22.4, 13.8 ; MS (ES+) m/z 463.1 (M + 1). Example 108 2-butyl-3-(4_{[2- Synthesis of (dimethylamino)ethyl]amino}phenyl> quinazoline-4(3H)·one

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-漠苯基）-2-丁基喹唑啉-4(3H)_酮置換3_(4m氯苯 基）-2-丁基♦唾啉_4(3H)，，及n，N-二甲基乙胺置換嗎福啉， 獲得2-丁基-3-(4-{[2仁甲胺基）乙基]胺基丨苯基）峻唑啉-4(3H)_ 酿I (45%) ’ 為無色固體：熔點 115-n6〇c ; lH nmr (3〇〇 MHz， CDC13) δ 8.26 (d，J = 1.5 Hz，1H)，7.76-7.64 (m，2H)，7.41 (td，J = 7·5, 1·5 Hz，1H)，7.02-6.95 (m，2H)，6.73-6.67 (m，2H)，4.70-4.64 (m，1H)， 3.24-3.17 (m，2H)，2.65 (t，J = 6.0 Hz，2H)，2.47 (t，J = 7.8 Hz，2H), 2.31 128409 -227- 200836743 (s，6H)，1.67 (五重峰，j =： 7.5 Hz，2H), 1.25 (六重峰，J = 7·5 Hz，2H)， 0.81 (t，J = 7·5 Ηζ，3Η) ; 13C NMR (75 ΜΗζ，CDC13) (5 163·0, 158.4, 148.8, 147.6, 134.2, 128.8, 127·1，126.9, 126.4, 126.2, 120.8, 113.3, 57·7, 45·0, 40.7, 35.6, 29.4, 22.4, 13·8 ; MS (ES+) m/z 365·1 (Μ + 1)· 實例109 2_丁基·3-[4_(4-甲基六氫吡畊小基）苯基]ρ奎唑啉-4(3Η)_酮之合成According to the procedure as described in Example 86, irrelevant changes were made using 3-(4-diphenyl)-2-butylquinazolin-4(3H)-one to replace 3-(4m chlorophenyl)- 2-butyl ♦ sinoline _4 (3H), and n, N-dimethylethylamine in place of morphine, to obtain 2-butyl-3-(4-{[2-methylamino)ethyl Amino phenyl phenyl thiazoline-4 (3H) _ Brewing I (45%) ' is a colorless solid: melting point 115-n6 〇c; lH nmr (3 〇〇 MHz, CDC13) δ 8.26 (d, J = 1.5 Hz, 1H), 7.76-7.64 (m, 2H), 7.41 (td, J = 7·5, 1·5 Hz, 1H), 7.02-6.95 (m, 2H), 6.73-6.67 (m, 2H) ), 4.70-4.64 (m, 1H), 3.24-3.17 (m, 2H), 2.65 (t, J = 6.0 Hz, 2H), 2.47 (t, J = 7.8 Hz, 2H), 2.31 128409 -227- 200836743 (s,6H), 1.67 (five peaks, j =: 7.5 Hz, 2H), 1.25 (six peaks, J = 7·5 Hz, 2H), 0.81 (t, J = 7·5 Ηζ, 3Η) 13C NMR (75 ΜΗζ, CDC13) (5 163·0, 158.4, 148.8, 147.6, 134.2, 128.8, 127·1, 126.9, 126.4, 126.2, 120.8, 113.3, 57·7, 45·0, 40.7, 35.6 , 29.4, 22.4, 13·8 ; MS (ES+) m/z 365·1 (Μ + 1)· Example 109 2_butyl·3-[4_(4-methylhexahydropyridinium Synthesis of Phenyl] hydroxy] quinazoline-4(3Η)-ketone

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）_2_ 丁基喹唑啉_4(3Η)_酮置換3-(4-溴基-2-氯苯 基）-2-丁基喹唑啉_4(3H)-酮，及1·甲基六氫吡畊置換嗎福啉， 獲得2_丁基-3·[4-(4-甲基六氫吡啤-1-基）苯基]4唑啉-4(3H)-酮 (45%)，為無色固體：熔點 115_116。〇 ; iHNMR(300 MHz，CDCl3) δ 8·24 (dd，J = 7.8, 1·2 Hz，1H)，7·73 (td5 J = 8.1，1·5 Hz，1H)，7.69 (dd，J =7.8, 1.2 Hz，1H)，7·42 (td，J = 7.5, 1·2 Hz，1H)，7.13-7-06 (m，2H)， 7·05-6_99 (m，2H)，3.35 (t，J = 4.8 Hz，4H)，2.68 (t，J = 4.8 Hz，4H)， 2.46-2.38 (m，5H)，1·65 (五重峰，J = 7.8 Hz，2H)，1.46 (六重峰，J = 7.5 /hz? 2H)? 0.80 (t5 J = 7.5 Hz, 3H) ； 13 C NMR (75 MHz, CDC13) δ 162.9, 158.0, 151.4, 147·6, 134.3, 128.8, 128.4, 127.0, 126.9, 126.4, 120.8, 116.4, 54.9, 48.5, 46.1，35.6, 29.3, 22·4, 13·8; MS (ES+) m/z 377·1 (Μ + 1). 實例110 4-[4-(2-丁基-4-酮基喹唑啉-3(4Η)·基）苯基]六氳吡啩-1-羧酸第 三-丁酯之合成 128409 -228- 200836743Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)_2-butylquinazoline-4(3Η)-one to replace 3-(4-bromo-2- Chlorophenyl)-2-butylquinazoline-4(3H)-one, and 1·methylhexahydropyrazine for the replacement of morphine, 2-butyl-3·[4-(4-methyl) Hexahydropyran-1-yl)phenyl]4oxazolyl-4(3H)-one (45%) as colorless solid: m.p. H; iHNMR (300 MHz, CDCl3) δ 8·24 (dd, J = 7.8, 1·2 Hz, 1H), 7·73 (td5 J = 8.1, 1. 5 Hz, 1H), 7.69 (dd, J =7.8, 1.2 Hz, 1H), 7.42 (td, J = 7.5, 1·2 Hz, 1H), 7.13-7-06 (m, 2H), 7·05-6_99 (m, 2H), 3.35 (t, J = 4.8 Hz, 4H), 2.68 (t, J = 4.8 Hz, 4H), 2.46-2.38 (m, 5H), 1·65 (five peaks, J = 7.8 Hz, 2H), 1.46 ( Hexagon peak, J = 7.5 /hz? 2H)? 0.80 (t5 J = 7.5 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) δ 162.9, 158.0, 151.4, 147·6, 134.3, 128.8, 128.4, 127.0, 126.9, 126.4, 120.8, 116.4, 54.9, 48.5, 46.1, 35.6, 29.3, 22·4, 13·8; MS (ES+) m/z 377·1 (Μ + 1). Example 110 4-[4 Synthesis of -(2-butyl-4-ketoquinazolin-3(4Η)-yl)phenyl]hexapyridin-1-carboxylic acid tert-butyl ester 128409 -228- 200836743

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-漠苯基）-2·丁基喹唑啉-4(3H)-酮置換3_(4-漠基冬氯苯 基）-2-丁基喹唑啉-4(3H)-顚I，及六氫吡畊+羧酸第三_丁酯置 換嗎福琳，獲得4-[4-(2丁基冰酮基喹唑p林-3(4H)-基）苯基]六氫 峨p井-1-魏酸第二-丁酯（55%)，為無色固體：1H NjyjR (3〇〇 MHz， CDC13) 5 8·24 (dt，J = 7.8, 〇·9 Hz，1H)，7.77-7.65 (m，2H)，7.43 (td，J = 7.5, 1.5 Hz，1H)，7.11 (d，J = 9.0 Hz，2H)，7.02 (J = 9·0 Hz，2H)，2.60 (t，J -5·1 Hz，4H)，3.22 (t，J - 5.1 Hz，4H)，2.46 (t，J = 7.5 Hz，2H)，1.70-1.57 (m，2H)，1.48 (s5 9H)，1.4 (六重峰，j = 7 2 Hz，2H)，〇 8〇 (t，j = 7 2 Hz， 3H) ； MS (ES+) m/z 463.3 (M + 1). 實例111 丁基六氫说咬-1_基苯基）峻峻淋-4(3H)-酮之合成Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-diphenyl)-2.butylquinazolin-4(3H)-one to replace 3-(4-Molyl chloride Phenyl)-2-butylquinazoline-4(3H)-顚I, and hexahydropyrazine + carboxylic acid tert-butyl ester to replace carbendene to obtain 4-[4-(2butyl ketone) Pyridyl p-lin-3(4H)-yl)phenyl]hexahydropurine p-well-1-dicarboxylic acid second-butyl ester (55%) as a colorless solid: 1H NjyjR (3〇〇MHz, CDC13) 5 8·24 (dt, J = 7.8, 〇·9 Hz, 1H), 7.77-7.65 (m, 2H), 7.43 (td, J = 7.5, 1.5 Hz, 1H), 7.11 (d, J = 9.0 Hz) , 2H), 7.02 (J = 9·0 Hz, 2H), 2.60 (t, J -5·1 Hz, 4H), 3.22 (t, J - 5.1 Hz, 4H), 2.46 (t, J = 7.5 Hz) , 2H), 1.70-1.57 (m, 2H), 1.48 (s5 9H), 1.4 (sixth peak, j = 7 2 Hz, 2H), 〇 8 〇 (t, j = 7 2 Hz, 3H); MS (ES+) m/z 463.3 (M + 1). Example 111 Synthesis of butyl hexahydro succinyl-1 phenyl phenyl)

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）-2-丁基喹唑啉_4(3H)_酮置換3_(冬溴基氯苯 基）-2-丁基喹嗤淋-4(3H&gt;_，及六氫吡啶置換嗎福啉，獲得2-丁基各(4-六氫吡啶-1-基苯基 &gt;奎唑啉-4(3H^酮（5〇%)，為無色 固體：熔點 131-133°C ; 4 NMR (300 MHz，CDC13) 5 8.24 (此，j = 7.8, 0·9 Hz，1H)，7.76-7.65 (m，2H)，7.42 (td，J = 7.5，1.5 Hz，1H)， 128409 -229- 200836743 7.09-6.98 (m，4H)，3.24 (t，J = 5.4 Hz，4H)，2.45 (t5 J = 7·8 HZ，2H)， 1.78-1.53 (m，6H)，1.31-U7 (m，4H)，0.80 (t，J = 7·5 Hz，3H) ; MS (ES+) m/z 362.2 (M + 1). 實例112 3-{[4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]胺基}六氫吡σ定·h 魏酸第三-丁酯之合成 ΗInconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)-2-butylquinazoline-4(3H)-one to replace 3-(t-bromochlorophenyl) )-2-butylquinoxaline-4 (3H&gt;_, and hexahydropyridine to replace morphine, to obtain 2-butyl each (4-hexahydropyridin-1-ylphenyl) quinazoline-4 (3H^ketone (5〇%) as a colorless solid: m.p. 131-133°C; 4 NMR (300 MHz, CDC13) 5 8.24 (here, j = 7.8, 0·9 Hz, 1H), 7.76-7.65 ( m, 2H), 7.42 (td, J = 7.5, 1.5 Hz, 1H), 128409 -229-200836743 7.09-6.98 (m, 4H), 3.24 (t, J = 5.4 Hz, 4H), 2.45 (t5 J = 7·8 HZ, 2H), 1.78-1.53 (m, 6H), 1.31-U7 (m, 4H), 0.80 (t, J = 7·5 Hz, 3H); MS (ES+) m/z 362.2 (M + 1). Example 112 3-{[4-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]amino}hexahydropyridinium·h Weilic acid third Synthesis of butyl ester

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）-2-丁基喹唑啉-4(3Η)-酮置換3-(4-溴基-2-氯笨 基）-2-丁基喹唑啉-4(3H&gt;酮，及3-胺基六氫吡啶-1-羧酸第三_ 丁酯置換嗎福啉，獲得3-{[4-(2-丁基-4-酮基喹唑啉-3(4H&gt;基） 苯基]胺基}六氫吡啶-1-羧酸第三-丁酯（30%)，為無色固體： MS (ES+) m/z 477.4 (Μ + 1). 實例113 2-丁基-3-[4-(四氫ρ比哈-3-基胺基）苯基]p查唾淋-4(3H)-酮二鹽酸 鹽之合成Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)-2-butylquinazolin-4(3Η)-one to replace 3-(4-bromo-) 2-Chlorophenyl)-2-butylquinazoline-4 (3H&gt; ketone, and 3-aminohexahydropyridine-1-carboxylic acid tert-butyl ester to replace morphine, to obtain 3-{[4 -(2-butyl-4-ketoquinazolin-3(4H&gt;yl)phenyl]amino}hexahydropyridine-1-carboxylic acid tert-butyl ester (30%) as colorless solid: MS (ES+) m/z 477.4 (Μ + 1). Example 113 2-butyl-3-[4-(tetrahydro-p-ha-3-ylamino)phenyl]p------(3H) -Synthesis of ketone dihydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用3-{[4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]胺基}四氫吡咯 -1·羧酸第三-丁酯置換[2-(2-丁基斗酮基喹唑啉-3(4H)-基）乙基] 胺基曱酸第三-丁酯，獲得2-丁基-3-[4-(四氫吡咯-3-基胺基） 128409 230- 200836743 苯基]喳唑啉-4(3H)_酮二鹽酸鹽（99%)，為無色固體：熔點 150-153〇C ； !H NMR (300 MHz, CD3OD) δ 8.30 (dd? J = 7.8? 1.2 Hz? 1H)，8.05 (td，J = 7.8, 1.2 Hz，1H)，7.83 (d，J = 8.4 Hz，1H)，7.76 (td，J = 7.5, 0.9 Hz，1H)，7.26 (d，J = 9·3 Hz，2H)，6.89 (d，J = 8.4 Hz，2H)， 4.46-4.27 (m，1H)，3.63-3.20 (m，4H)，2.81 (t，J = 8·1 Hz，2H)，2.41 (六 重峰，J = 7.5 Hz，1H)，2.18-2.07 (m，1H)，1.73-1.60 (m，2H)，L30 (六重 峰，J = 7.5 Hz，2H)，0.78 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz， CD3OD) 5 165.3, 159.4, 148.7, 136.8, 136.5, 129.1，128.7, 123.3, 119.1， 118.6, 113.5, 113.2, 52.0, 50.0, 44.1，32.8, 30.2, 29.0, 22.0, 12.1 ; MS (ES+) m/z 363.2 (M + 1). 實例114 2-丁基-3-(4-六氫外b p井-1-基苯基）邊唾淋-4(3H)-酮二鹽酸鹽之 合成According to the procedure as described in Example 74, an insignificant change was made using 3-{[4-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]amino} Tert-butyl ester of tetrahydropyrrole-1·carboxylic acid to replace [2-(2-butylbuxenylquinazolin-3(4H)-yl)ethyl]amino-decanoic acid tert-butyl ester, obtained 2-butyl-3-[4-(tetrahydropyrrol-3-ylamino) 128409 230- 200836743 Phenyl]oxazoline-4(3H)-one dihydrochloride (99%) as a colorless solid : melting point 150-153 〇C; !H NMR (300 MHz, CD3OD) δ 8.30 (dd? J = 7.8? 1.2 Hz? 1H), 8.05 (td, J = 7.8, 1.2 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.76 (td, J = 7.5, 0.9 Hz, 1H), 7.26 (d, J = 9·3 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 4.46- 4.27 (m,1H), 3.63-3.20 (m,4H), 2.81 (t, J = 8·1 Hz, 2H), 2.41 (sixfold, J = 7.5 Hz, 1H), 2.18-2.07 (m, 1H), 1.73-1.60 (m, 2H), L30 (sixfold, J = 7.5 Hz, 2H), 0.78 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CD3OD) 5 165.3, 159.4, 148.7, 136.8, 136.5, 129.1, 128.7, 123.3, 119.1, 118.6, 113.5, 113.2, 52.0, 50.0, 44.1, 32.8, 30.2, 29.0, 22.0, 12.1; MS (ES+) m/z 363.2 (M + 1). Example 114 2-butyl-3-(4-hexahydro-exo bp well-1-ylphenyl) sedative-4 Synthesis of 3H)-ketodihydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用4-[4-(2-丁基冰酮基喹唑啉-3(4H)-基）苯基]六氫吡畊-1-羧酸 第三-丁酯置換[2-(2-丁基_4_酮基喹唑啉-3(4H)·基）乙基]胺基甲 酸第三-丁 i旨，獲得2-丁基-3-(4-六氫吡啡小基苯基）峻唑啉 -4(3H)-酮二鹽酸鹽（99%)，為無色固體·· 4 NMR (300 MHz， CD3OD) 5 8.31 (dd5 J = 8·1，0.9 Hz，1H)，8.06 (ddd，J = 7.5, 7.5, 1.2 Hz, 1H)，7.85 (d，J = 8·1 Hz，1H)，7.75 (ddd，J = 7.5, 7.5, 0.6 Hz，1H)，7.40 (d， J = 9 Hz，2H)，7.25 (d，J = 9 Hz，2H)，3.57 (t，J = 5.1 Hz，4H)，3.40 (t，J = 128409 -231 - 200836743 5.1 Hz，4H)，2·79 (t，J = 9.6 Hz，2H)，1·67 (五重峰，J = 7·5 Hz，2H)，1.29 (六重峰，J = 7·5 Hz，2H)，0.79 (t，J = 7·5 Hz，3H) ; 13 C NMR (75 MHz， CD3OD) 6 164.7, 159.5, 151.6, 137.5, 136.4, 129.0, 128.8, 127.7, 126.2, 119.1，116.7, 45.4, 43.2, 32.9, 29.0, 22.0, 12.1 ; MS (ES+) m/z 363.2 (M + 1). 實例115 2·丁基-3-[4·(六氫p比咬-3-基胺基）苯基]峻唾淋-4(3H)-S同二鹽酸 鹽之合成According to the procedure as described in Example 74, an insignificant change was made using 4-[4-(2-butylrhosylquinazolin-3(4H)-yl)phenyl]hexahydropyrazine-1 -carboxylic acid tert-butyl ester replacement [2-(2-butyl-4-yl-quinazolin-3-(4H)-yl)ethyl]aminocarboxylic acid third-buty, obtained 2-butyl Benzyl-3-(4-hexahydropyridinylphenyl)-trazoline-4(3H)-one dihydrochloride (99%) as a colorless solid.· 4 NMR (300 MHz, CD3OD) 5 8.31 (dd5 J = 8·1, 0.9 Hz, 1H), 8.06 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.85 (d, J = 8·1 Hz, 1H), 7.75 (ddd, J = 7.5, 7.5, 0.6 Hz, 1H), 7.40 (d, J = 9 Hz, 2H), 7.25 (d, J = 9 Hz, 2H), 3.57 (t, J = 5.1 Hz, 4H), 3.40 (t, J = 128409 -231 - 200836743 5.1 Hz, 4H), 2·79 (t, J = 9.6 Hz, 2H), 1.67 (five peaks, J = 7·5 Hz, 2H), 1.29 (six peaks) , J = 7·5 Hz, 2H), 0.79 (t, J = 7·5 Hz, 3H); 13 C NMR (75 MHz, CD3OD) 6 164.7, 159.5, 151.6, 137.5, 136.4, 129.0, 128.8, 127.7 , 126.2, 119.1, 116.7, 45.4, 43.2, 32.9, 29.0, 22.0, 12.1; MS (ES+) m/z 363.2 (M + 1). Example 115 2·butyl-3 Synthesis of -[4·(hexahydrop-biti-3-ylamino)phenyl]junsaolin-4(3H)-S with dihydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用3-{[4-(2-丁基-4·酮基p奎峻4 ·3(4Η)_基）苯基]胺基}六氫ϊΐ比咬 -1-羧酸第三-丁酯置換[2-(2-丁基-4-酮基喳唑啉-3(4Η)-基）乙基] 胺基甲酸第三-丁酯，獲得2·丁基·3-[4-(六氫吡啶-3·基胺基） 苯基 &gt;奎°坐淋_4(3Η)_酮二鹽酸鹽（53°/。），為無色固體：、j：容點 157-159〇C ； NMR (300 MHz5 CD3OD) δ 8.29 (dd5 J = 7.8, 1.2 Hz, 1H)，8.05 (ddd，J = 7.8, 7.8, 1·2 Hz，1H)，7.83 (d，J = 8·1 Hz，1H)，7.76 (ddd，J = 7.8，7.8，0.6 Hz，1H)，7.24 (d，J = 9.0 Hz，2H)，6.91 (d，J = 9.0 Hz, 2H)? 3.89-3.78 (m5 1H)? 3.64 (s? 2H)5 3.50 (dd? J = 12.3, 3.3 Hz5 1H)5 3.38-3.27 (m? 1H), 3.02 (dt, J = 9.1, 1.5 Hz, 1H)? 2.93-2.77 (m, 3H), 2.22-2.02 (m，2H)，1.97-1.81 (m，1H)，1.75-1.60 (m，3H)，1·30 (六重峰，J =7.2 Hz, 2H)，0.79 (t，J = 7.2 Hz，3H) ; MS (ES+) m/z 377.3 (Μ + 1). 128409 -232 - 200836743 實例116 3-(4-嗎福琳-4-基苯基）-2-苯基峻σ坐淋-4(3H)-綱之合成According to the procedure as described in Example 74, an insignificant change was used, using 3-{[4-(2-butyl-4. keto p-kuban 4 ·3(4Η)-yl)phenyl]amine } hexahydropyrene-bite-1-carboxylic acid tert-butyl ester replacement [2-(2-butyl-4-ketooxazoline-3(4Η)-yl)ethyl]aminocarbamic acid third- Butyl ester, which obtained 2·butyl·3-[4-(hexahydropyridin-3-ylamino)phenyl]&gt; quinine _4(3Η)-keto dihydrochloride (53°/.) , as a colorless solid: j: 157-159 〇C; NMR (300 MHz5 CD3OD) δ 8.29 (dd5 J = 7.8, 1.2 Hz, 1H), 8.05 (ddd, J = 7.8, 7.8, 1·2 Hz , 1H), 7.83 (d, J = 8·1 Hz, 1H), 7.76 (ddd, J = 7.8, 7.8, 0.6 Hz, 1H), 7.24 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H)? 3.89-3.78 (m5 1H)? 3.64 (s? 2H)5 3.50 (dd? J = 12.3, 3.3 Hz5 1H)5 3.38-3.27 (m? 1H), 3.02 (dt, J = 9.1, 1.5 Hz, 1H)? 2.93-2.77 (m, 3H), 2.22-2.02 (m, 2H), 1.97-1.81 (m, 1H), 1.75-1.60 (m, 3H), 1·30 (six Heavy peak, J = 7.2 Hz, 2H), 0.79 (t, J = 7.2 Hz, 3H); MS (ES+) m/z 377.3 (Μ + 1). 128409 -232 - 200836743 Example 116 3-(4-? Fulin-4-based Synthesis of phenyl)-2-phenyl sigmoid sputum-4(3H)-class

於嗎福琳-4-基苯基）-2-苯基·2,3_二氯峻哇琳-4(1H)-酉同 (〇·15克’ 0.29毫莫耳）在氯仿（5毫升）中之懸浮液内，添加2,3-二氯-5,6-二氰基-i，4-苯醌（〇·〇7克，0.29毫莫耳）。將反應混合 物於環境溫度下攪拌兩小時。蒸發氯仿，並使殘留物接受 管柱層析（在己烷中之50%醋酸乙酯），獲得3-(4-嗎福啉-4-基 苯基）-2-苯基喹唑啉-4(3H)-酮（0.090克，83%)，為無色固體： 熔點 172-174°C ; 4 NMR (300 MHz，CDC13) 5 8.33 (d，J = 7.8 Hz， 1H)，7·82_7·75 (m，2H)，7.54-7.47 (m，1H)，7.37-7.32 (m，2H)，7-26-7.18 (m，3H)，7.00 (d，J = 9·0 Hz，2H)，6.78 (d，J = 9.0 Hz，2H)，3·81 (t，J = 4.8 Hz5 4H)? 3.11 (t? J = 4.8 Hz5 4H) ； 13 C NMR (75 MHz, CD3 OD) δ 162.6, 155.6, 150.7, 147.5, 135.6, 134.6, 129.6, 129.2, 129.0, 128.0, 127.7, 127.2, 120.9, 115.4, 66.7, 48.8. MS (ES+) m/z 384.8 (M + 1). 實例117 3-{[4-(2-丁基-4-酮基喹唑啉-3(4H)_基）苯基]胺基}一氮四圜小 羧酸第三-丁 i旨之合成吗福福琳-4-ylphenyl)-2-phenyl·2,3_dichloro-wowline-4(1H)-酉同(〇·15g '0.29mmol) in chloroform (5ml In the suspension, 2,3-dichloro-5,6-dicyano-i,4-benzoquinone (7 g, 0.29 mmol) was added. The reaction mixture was stirred at ambient temperature for two hours. The chloroform was evaporated, and the residue was subjected to column chromatography (50% ethyl acetate in hexane) to give 3-(4-hofolin-4-ylphenyl)-2-phenylquinazoline- 4(3H)-one (0.090 g, 83%) as colorless solid: mp 172-174 ° C; 4 NMR (300 MHz, CDC13) 5 8.33 (d, J = 7.8 Hz, 1H), 7·82_7· 75 (m, 2H), 7.54-7.47 (m, 1H), 7.37-7.32 (m, 2H), 7-26-7.18 (m, 3H), 7.00 (d, J = 9·0 Hz, 2H), 6.78 (d, J = 9.0 Hz, 2H), 3·81 (t, J = 4.8 Hz5 4H)? 3.11 (t? J = 4.8 Hz5 4H) ; 13 C NMR (75 MHz, CD3 OD) δ 162.6, 155.6 , 150.7, 147.5, 135.6, 134.6, 129.6, 129.2, 129.0, 128.0, 127.7, 127.2, 120.9, 115.4, 66.7, 48.8. MS (ES+) m/z 384.8 (M + 1). Example 117 3-{[4 -(2-Butyl-4-ketoquinazolin-3(4H)-yl)phenyl]amino}mononitrotetracarboxylic acid carboxylic acid

按照如實例86中所述之程序，施行無關緊要之改變，使 128409 -233 - 200836743 用3-(4-溴苯基）_2_ 丁基p奎唑淋-4(3H)-酮置換3-(4-溴基-2-氯苯 基）-2-丁基邊唾琳-4(3H)-酮，及3-胺基一氮四圜-μ魏酸第三-丁酯置換嗎福啉，獲得3-{[4-(2-丁基-4-酮基喹唑啉_3(4H)_基） 苯基]胺基卜氮四圜-1-羧酸第三-丁酯（49%)，為無色固體： 1 H NMR (300 MHz，CDC13) (5 8.26 (d，J = 7·5 Hz，1H)，7.79-7.66 (m， 2H)，7.44 (ddd，J = 6.9, 6.9, 1·2 Hz，1H)，7.07-7.01 (m，2H)，6.65-6.58 (m， 2H)，4.37-4.21 (m，4H)，3.82-3.75 (m，2H)，2.47 (t，J = 7.5 Hz，2H)， 1.72-1.60 (m，2H)，1.45 (s，9H)，1.31-1.18 (m，2H)，0.82 (t，J = 7.5 Hz， 3H) ； MS (ES+) m/z 449 (M + 1). 實例118 3-[4-(—氮四圜_3-基胺基）笨基]_2-丁基p奎唾琳-4(3H)-酮鹽酸鹽 之合成According to the procedure as described in Example 86, an insignificant change was made such that 128409-233 - 200836743 was replaced with 3-(4-bromophenyl)_2-butyl p-quinazolin-4(3H)-one 3-( 4-bromo-2-chlorophenyl)-2-butyl-sialin-4(3H)-one, and 3-amino-tetrazine-μ-weilic acid tert-butyl ester to replace the morphine, 3-{[4-(2-Butyl-4-ketoquinazolin-3-3(4H)-yl)phenyl]aminopyridinium-4-carboxylic acid tert-butyl ester (49%) ), as a colorless solid: 1 H NMR (300 MHz, CDC13) (5 8.26 (d, J = 7. 5 Hz, 1H), 7.79-7.66 (m, 2H), 7.44 (ddd, J = 6.9, 6.9, 1·2 Hz, 1H), 7.07-7.01 (m, 2H), 6.65-6.58 (m, 2H), 4.37-4.21 (m, 4H), 3.82-3.75 (m, 2H), 2.47 (t, J = 7.5 Hz, 2H), 1.72-1.60 (m, 2H), 1.45 (s, 9H), 1.31-1.18 (m, 2H), 0.82 (t, J = 7.5 Hz, 3H); MS (ES+) m/z 449 (M + 1). Example 118 Synthesis of 3-[4-(-aza-tetradecyl-3-ylamino)phenyl]_2-butyl p-quineline-4(3H)-one hydrochloride

H NH N

按照如實例74中所述之程序，施行無關緊要之改變，使 用3-{[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]胺基}一氮四圜 1_叛酸第三_丁酯置換[2-(2-丁基-4-酮基π奎唾淋-3(4H)-基）乙基] 胺基甲酸第三-丁酯，獲得3-[4-(—氮四圜-3-基胺基）苯基]-2-丁基喹唑啉-4(3Η)·_鹽酸鹽（92%)，為無色固體：熔點155-160 °C ； NMR (300 MHz, CD3OD) δ 8.32 (d5 J = 7.8 Hz5 1H)? 8.07 (dd? J 二 7_8, 7.8 Hz，1H)，7.85 (d，J = 8.4 Hz，1H)，7.78 (dd，J = 7.8, 7_8 Hz， 1H)，7.28 (d，J = 8.4 Hz，2H)，6.82 (d，J = 8.4 Hz，2H)，4.68-4.41 (m，3H)， 4.11-4.01 (m，2H)，2.87-2.77 (m，2H)，1.76-1.62 (m，2H)，1.38-1.23 (m， 128409 -234 - 200836743 2H)，0.81 (t，J = 7.5 Hz，3H) ; 13C NMR (75 MHz，CD3OD) 6 166.7, 160.8, 149.5, 138.2, 137.9, 130.5, 130.3, 129.2, 125.1，120.5, 120.1，114.6, 54.9, 46.4, 34.2, 30.5, 23.5, 13.6 ; MS (ES+) m/z 349.3 (M + 1). 實例119 2-丁基 _3-{4-[(7aS)-3-酮基四氫-1H-P比略并[l，2_c]咪唾 _2(3H)_基]苯 基奎唑琳-4(3H&gt;酮之合成According to the procedure as described in Example 74, an insignificant change was made using 3-{[4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]amino} Nitrogen tetramine-1_remediation third-butyl ester replacement [2-(2-butyl-4-keto π quinolate-3(4H)-yl)ethyl] carbamic acid tert-butyl ester , 3-[4-(-Aza-tetradecylidene-3-ylamino)phenyl]-2-butylquinazoline-4(3Η)·_ hydrochloride (92%), m. 155-160 °C; NMR (300 MHz, CD3OD) δ 8.32 (d5 J = 7.8 Hz5 1H)? 8.07 (dd? J 2 7_8, 7.8 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.78 (dd, J = 7.8, 7_8 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 4.68-4.41 (m, 3H), 4.11-4.01 (m, 2H), 2.87-2.77 (m, 2H), 1.76-1.62 (m, 2H), 1.38-1.23 (m, 128409 - 234 - 200836743 2H), 0.81 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CD3OD) 6 166.7, 160.8, 149.5, 138.2, 137.9, 130.5, 130.3, 129.2, 125.1, 120.5, 120.1, 114.6, 54.9, 46.4, 34.2, 30.5, 23.5, 13.6 ; MS (ES+) m /z 349.3 (M + 1). Example 119 2-butyl_3-{4-[(7aS)-3-ketotetrahydro-1H-P ratio slightly [l 2_c] imidazol salivary _2 (3H) _ yl] phenyl oxazole Jikui Lin -4 (3H &gt; one Synthesis of

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）-2-丁基喹唑啉-4(3H)-酮置換3-(4-溴基-2-氯苯 基）-2-丁基喳唑啉-4(3H)-酮，及（S)-2-(胺基甲基）四氫吡咯-1-羧 酸第三-丁酯置換嗎福啉，獲得2-丁基-3-{4_[(7aS)-3-酮基四氫 -1H-吡咯并[l，2-c]咪唑-2(3H)-基]苯基 &gt;奎唑啉-4(3H)-酮（59%)，為 無色固體：熔點 150-152°C ; iHNMR (300 MHz，CDC13) 5 8.29-8.22 (m，1H)，7.83-7.66 (m，4H)，7.49-7.39 (m，1H)，7.24-7.17 (m，2H)， \ 4.11-3.71 (m5 4H)5 3.25-3.14 (m5 1H)? 2.45 (t5 J = 7.5 Hz5 2H)5 2.19-1.19 (m，8H)，0.83 (t，J = 7.5 Hz, 3H) ; 13 C NMR (75 MHz，CDC13) 5 162.6, 160.4, 157.5, 147.4, 140.9, 134.4, 131.2, 128.6, 126.9, 126.8, 126.4, 120.6, 118.2, 118.1，55.3, 47.9, 45.6, 35.5, 31.4, 29.2, 25.1，22.3, 13.7 ; MS (ES+) m/z 403.2 (M + 1). 實例120 (3R)-3-{[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]胺基}六氫吡啶 -1-羧酸第三-丁酯之合成 128409 -235 - 200836743Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)-2-butylquinazolin-4(3H)-one to replace 3-(4-bromo-) 2-chlorophenyl)-2-butyloxazoline-4(3H)-one, and (S)-2-(aminomethyl)tetrahydropyrrole-1-carboxylic acid tert-butyl ester replacement? Fulin, obtaining 2-butyl-3-{4_[(7aS)-3-ketotetrahydro-1H-pyrrolo[l,2-c]imidazole-2(3H)-yl]phenyl&gt; Oxazoline-4(3H)-one (59%) as colorless solid: m.p. 150-152°C; iHNMR (300 MHz, CDC13) 5 8.29-8.22 (m,1H), 7.83-7.66 (m,4H) , 7.49-7.39 (m, 1H), 7.24 - 7.17 (m, 2H), \ 4.11-3.71 (m5 4H) 5 3.25-3.14 (m5 1H)? 2.45 (t5 J = 7.5 Hz5 2H) 5 2.19-1.19 ( m,8H), 0.83 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) 5 162.6, 160.4, 157.5, 147.4, 140.9, 134.4, 131.2, 128.6, 126.9, 126.8, 126.4, 120.6 , 118.2, 118.1, 55.3, 47.9, 45.6, 35.5, 31.4, 29.2, 25.1, 22.3, 13.7; MS (ES+) m/z 403.2 (M + 1). Example 120 (3R)-3-{[4-( Synthesis of 2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]amino}hexahydropyridine-1-carboxylic acid tert-butyl ester 128409 -235 - 20083 6743

用3-(4·溴苯基）_2_ 丁基喹唑啉-4(3H)-酮置換3-(4-溴基·2_氯苯 基）-2-丁基喹唑啉_4(3Η).，及⑻各胺基六氫吡啶小羧酸第三 -丁醋置換嗎福啉，獲得（3R)-3-{[4-(2-丁基-4·酮基喳唑啉-3(4Η)-基）苯基]胺基}六氫吡啶-μ羧酸第三-丁酯（61%)，為無色固 按照如實例86中所述之程序，施行無關緊要之改變，使 體· 1H NMR (300 MHz，CDC13) 6 8.26 (d，J = 7.8 Ηζ，1Η)，7.79-7.65 (m，2H)，7.48-7.39 (m，lH)，7.06-6.97 (m，2H)，6.77-6.69 (m，2H)，4.16-3.66 (m，3H)，3.50-2.82 (m，3H)，2.49 (t，J = 7·5 Hz，2H)，2.08-1.20 (m， 17H)，0.83 (t，J = 7·5 Hz，3H) ; MS (ES+) m/z 477.3 (M + 1). 實例121 2-丁基-3-{4-[(3R)-六氫P比啶-3-基胺基]苯基}峻峻啦-4(3H)-酮鹽 酸鹽之合成Displacement of 3-(4-bromo-2-cyanophenyl)-2-butylquinazoline _4 (3Η) with 3-(4-bromophenyl)_2-butylquinazolin-4(3H)-one And (8) each of the amine hexahydropyridine small carboxylic acid tert-butyl vinegar substituted morphine to obtain (3R)-3-{[4-(2-butyl-4. ketooxazoline-3) (4Η)-yl)phenyl]amino}hexahydropyridine-μcarboxylic acid tert-butyl ester (61%), colorless solid according to the procedure described in Example 86, insignificant change, body · 1H NMR (300 MHz, CDC13) 6 8.26 (d, J = 7.8 Ηζ, 1 Η), 7.79-7.65 (m, 2H), 7.48-7.39 (m, lH), 7.06-6.97 (m, 2H), 6.77 -6.69 (m, 2H), 4.16-3.66 (m, 3H), 3.50-2.82 (m, 3H), 2.49 (t, J = 7·5 Hz, 2H), 2.08-1.20 (m, 17H), 0.83 (t, J = 7·5 Hz, 3H); MS (ES+) m/z 477.3 (M + 1). Example 121 2-butyl-3-{4-[(3R)-hexahydro-P-pyridine- Synthesis of 3-aminoamino]phenyl}junji-4(3H)-one hydrochloride

按照如實例74中所述之程序，施行無關緊要之改變，使 用（3R)-3-{[4_(2·丁基冰酮基喳唑啉-3(4H)-基）苯基]胺基}六氫吡 啶-1-羧酸第三-丁酯置換[2-(2-丁基-4-酮基喹唑啉-3(4H)-基）乙 基]胺基甲酸第三-丁酯，獲得2-丁基-3-{4-[(3R)-六氫吡啶-3-基 胺基]苯基}喳唑啉-4(3H)-酮鹽酸鹽（80%)，為無色固體··熔點 175-185〇C ； !H NMR (300 MHz, CD3OD) ά 8.32 (d5 J = 7.8 Hz5 1H)? 8.07 (ddd，J = 7.8, 7.8, 1·2 Hz，1H)，7·88_7·75 (m，2H)，7.25 (d，J = 8·7 Hz， 128409 -236 - 200836743 2H)，6.91 (d，J = 8.7 Hz，2H)，3.91-3.78 (m，1H)，3.57-3.48 (m，1Η)， 3.41-3.31 (m，1H)，3.11-2.77 (m，4H)，2.23-1.60 (m，6H)，1.40-1.25 (m， 2H)5 0.82 (t? J = 7.2 Hz? 3H) ； 13 C NMR (75 MHz, CD3OD) δ 166.8? 160.9, 150.0, 138.3, 137.9, 130.5, 130.2, 130.1，129.2, 124·3, 120.5, 120.1， 114.6, 114.2, 48.3, 47.7, 45.1，34.3, 30.5, 29.7, 23.5, 22.1，13.6 ; MS (ES+) m/z 377.3 (M + 1). 實例122 3-[4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯氧基]四氫吡咯-1-羧酸 第三-丁酯之合成According to the procedure as described in Example 74, an irrelevant change was used using (3R)-3-{[4_(2·butylglycosyloxazoline-3(4H)-yl)phenyl]amine } hexahydropyridine-1-carboxylic acid tert-butyl ester replacement [2-(2-butyl-4-ketoquinazolin-3(4H)-yl)ethyl]carbamic acid tert-butyl ester , 2-butyl-3-{4-[(3R)-hexahydropyridin-3-ylamino]phenyl}oxazoline-4(3H)-one hydrochloride (80%) was obtained as colorless Solid · · melting point 175-185 〇 C ; !H NMR (300 MHz, CD3OD) ά 8.32 (d5 J = 7.8 Hz5 1H)? 8.07 (ddd, J = 7.8, 7.8, 1·2 Hz, 1H), 7· 88_7·75 (m, 2H), 7.25 (d, J = 8·7 Hz, 128409 -236 - 200836743 2H), 6.91 (d, J = 8.7 Hz, 2H), 3.91-3.78 (m, 1H), 3.57 -3.48 (m,1Η), 3.41-3.31 (m,1H),3.11-2.77 (m,4H),2.23-1.60 (m,6H),1.40-1.25 (m, 2H)5 0.82 (t? J = 7.2 Hz? 3H) ; 13 C NMR (75 MHz, CD3OD) δ 166.8? 160.9, 150.0, 138.3, 137.9, 130.5, 130.2, 130.1, 129.2, 124·3, 120.5, 120.1, 114.6, 114.2, 48.3, 47.7, 45.1, 34.3, 30.5, 29.7, 23.5, 22.1, 13.6; MS (ES+) m/z 377.3 (M + 1). Example 122 3-[4-(2-butyl Synthesis of -4-ketoquinazolin-3(4H)-yl)phenoxy]tetrahydropyrrole-1-carboxylic acid tert-butyl ester

於2-丁基-3-(4-羥苯基 &gt;奎唑啉·4(3Η)_酮（0.38克，1.29毫莫耳） 在四氫呋喃（10毫升）中之溶液内，在環境溫度下，添加3_ 羥基四氫吡咯-1-羧酸第三-丁酯（0·36克，1.94毫莫耳）、三苯 膦（0.51克，1.94毫莫耳）及偶氮二羧酸二乙酯（〇·35毫升，194 毫莫耳）。將混合物於環境溫度下攪拌十六小時。使混合物 在真空中濃縮，產生殘留物，使其藉急驟式層析純化，獲 得3-[4-(2-丁基斗酮基喳唑啉_3(4Η&gt;基）苯氧基]四氫吡咯小羧 酸第三-丁酯：MS (ES+) m/z 464.3 (Μ + 1). 實例123 2 丁基3 [4 (四氫p比各j基氧基）苯基]p奎唾琳_4(犯)·酮二鹽酸 鹽之合成 128409 -237 - 200836743In a solution of 2-butyl-3-(4-hydroxyphenyl) quinazoline 4(3Η)-one (0.38 g, 1.29 mmol) in tetrahydrofuran (10 mL) at ambient temperature , adding 3 - hydroxytetrahydropyrrole-1-carboxylic acid tert-butyl ester (0 · 36 g, 1.94 mmol), triphenylphosphine (0.51 g, 1.94 mmol) and diethyl azodicarboxylate (〇·35 ml, 194 mmol). The mixture was stirred at ambient temperature for a period of sixteen hours. The mixture was concentrated in vacuo to yield residue which was purified by flash chromatography to afford 3-[4-( 2-butyl ketone oxazoline _3 (4 Η > yl) phenoxy] tetrahydropyrrole carboxylic acid tert-butyl ester: MS (ES+) m/z 464.3 (Μ + 1). Example 123 2 Synthesis of butyl 3 [4 (tetrahydrop to each j-yloxy)phenyl]p-quineline_4(criminal)·keto-dihydrochloride 128409 -237 - 200836743

按…、如貝例74中所述之程序，施行無關緊要之改變，使 用3·[4·(2_丁基-4-_基峻唾琳部H)_基）苯氧基]四氫吡洛小魏 西文第二-丁 g曰置換[2_(2-丁基I酮基喹唑啉_3^Η)_基）乙基]胺基 甲酸第二-丁酯，獲得2-丁基各[4_(四氫吡咯各基氧基）苯基] 4唾琳-4(3Η)-嗣二鹽酸鹽（62%)，為無色固體：熔點125_145 °C ； 'H NMR (300 MHz5 CD3OD) 5 8.24 (dd? J = 8.1? 1.2 Hz5 1H)? 7.97-7.89 (m，1H)，7.74 (d，了 = 8·1 Hz，1H)，7.66-7.59 (m，1H)，7.43-7.36 (m，2H)，7.26-7.19 (m，2H)，5.36-5.30 (m，1H)，3.65-3.46 (m，4H)， 2.63-2.55 (m，2H)，2.44-2.35 (m，2H)，1.73-1.61 (m，2H)，1.35-1.21 (m， 2H)，0·82 (t，J = 7·5 Hz，3H) ; 13C NMR (75 MHz，CD3OD) δ 160.0, 158.8, 136.8，131.2，131.1，129.0, 128.3，124.9, 121.2, 118.0, 117.9, 77.4, 52.0, 45.3, 35.6, 31.7, 30.4, 23.4, 13.8 ; MS (ES+) m/z 364.2 (M + 1). 實例124 2-(4-溴苯基）-3·丁基p奎唾淋-4(3H)-酮之合成According to the procedure described in Example 74, the inconsequential change was made using 3·[4·(2_butyl-4-yl-based sulphate H)-yl)phenoxy]tetrahydro Pyridine, Weiweiwen, second-butyryl hydrazine, [2-(2-butyl 1 ketoquinazoline _3^Η)-yl)ethyl]carbamic acid, second-butyl ester, 2-butyl each [4_(Tetrahydropyrrolidinyloxy)phenyl] 4 sialin-4(3Η)-indole dihydrochloride (62%) as colorless solid: m.p. 125-145 ° C; 'H NMR (300 MHz5 CD3OD) 5 8.24 (dd? J = 8.1? 1.2 Hz5 1H)? 7.97-7.89 (m, 1H), 7.74 (d, = 8·1 Hz, 1H), 7.66-7.59 (m, 1H), 7.43-7.36 ( m,2H), 7.26-7.19 (m,2H), 5.36-5.30 (m,1H), 3.65-3.46 (m,4H), 2.63-2.55 (m,2H),2.44-2.35 (m,2H), 1.73-1.61 (m, 2H), 1.35-1.21 (m, 2H), 0·82 (t, J = 7·5 Hz, 3H); 13C NMR (75 MHz, CD3OD) δ 160.0, 158.8, 136.8, 131.2 , 131.1, 129.0, 128.3, 124.9, 121.2, 118.0, 117.9, 77.4, 52.0, 45.3, 35.6, 31.7, 30.4, 23.4, 13.8; MS (ES+) m/z 364.2 (M + 1). Example 124 2-( Synthesis of 4-bromophenyl)-3·butyl p-quinone- 4(3H)-one

於2-(4-溴苯基）-3-丁基-2,3-二氫p奎峻琳·4(1Η)·8同（0.220克， 0.62毫莫耳）在氯仿（15毫升）中之經攪拌溶液内，添加2,3_二 氣-5,6-二氰基·對-苯g昆（0.154克，0·68毫莫耳）。將混合物於環 土兄溫度下授掉兩小時。在真空下移除溶劑。使殘留物接受 管柱層析（醋酸乙酯/己烷，1/8)，獲得2-(4-溴苯基）-3-丁基峻 128409 -238 - 200836743 唑啉-4(3H)-酮（0.215 克，100%): iH NMR (300 MHz，CDC13) 5 8.34-8.27 (m，1H)，7.79-7.62 (m，4H)，7.54-7.45 (m，1H)，7.44-7.37 (m， 2H)，3.95 (t，J = 7.0 Hz，3H)，1.63-1.50 (m，2H)，1.26-UO (m，2H)，0.78 (t， J = 7.0 Hz，3H) ; MS (ES+) m/z 357.1 (M + 1)，359.1 (M + 1). 實例125 3-(4-(3-丁基-4-酮基-3,4-二氫p奎嗤4 -2-基）苯基胺基）四氫p比嘻 •1-羧酸第三-丁酯之合成2-(4-Bromophenyl)-3-butyl-2,3-dihydrop-quineline·4(1Η)·8 with (0.220 g, 0.62 mmol) in chloroform (15 mL) In the stirred solution, 2,3_di-gas-5,6-dicyano-p-benzoquinone (0.154 g, 0·68 mmol) was added. The mixture was allowed to stand for two hours at the temperature of the ring. The solvent was removed under vacuum. The residue was subjected to column chromatography (ethyl acetate/hexanes, 1/8) to give 2-(4-bromophenyl)-3-butyl s s s s s s s s s s s s s s s s s 0.215 g, 100%): iH NMR (300 MHz, CDC13) 5 8.34-8.27 (m, 1H), 7.79-7.62 (m, 4H), 7.54-7.45 (m, 1H), 7.44-7.37 (m, 2H ), 3.95 (t, J = 7.0 Hz, 3H), 1.63-1.50 (m, 2H), 1.26-UO (m, 2H), 0.78 (t, J = 7.0 Hz, 3H); MS (ES+) m/ z 357.1 (M + 1), 359.1 (M + 1). Example 125 3-(4-(3-butyl-4-keto-3,4-dihydrop-quine-4-yl)phenyl Synthesis of Amino)Tetrahydrop-Phenyl-1-carboxylic Acid Tri-Butyl Ester

於2-(4-溴苯基）-3_ 丁基p奎嗤琳_4(3H)_酮（0.215克，0.62毫莫 耳）、l-Boc-3-胺基四氫吡咯（0.173克，0.93毫莫耳）及2,2，-雙（二 苯膦）-1，Γ-聯莕在甲苯（15毫升）中之經攪拌溶液内，添加參 (二苯亞甲基丙酮）二把（0.045克，〇·〇5毫莫耳），接著添加第 二-丁醇納（0.179克，1.86毫莫耳）。將混合物於i〇〇°c下搜拌 十八小時。使混合物經過矽藻土墊過濾，在真空中濃縮漉 液。使殘留物接受管柱層析（醋酸乙酯/己烷，1/2)，獲得 3-(4-(3-丁基斗酮基-3,4-二氫喳唑啉-2-基）苯基胺基）四氫吡嘻 -1-羧酸第三-丁酯（〇_250 克，87%) : 1H NMR (300 MHz，CDC13) 5 8.32-8.26 (m，1H)，7.75-7.66 (m，2H)，7.49-7.41 (m，1H)，7·35 (d，J = 8.5 Hz，2H)，6.67 (d，J = 8·5 Hz，2H)，4.18-3.95 (m，4H)，3.83-3.61 (m，1H)， 3.56-3.39 (m，2H)，3.37-3.17 (m，1H)，2.30-2.14 (m，1H)，2·0(Μ·82 (m， 1H)，1.68-1.53 (m，2H)，1.46 (s，9H)，1.28] .11 (m，2H)，0.78 (t5 J = 7.0 Hz， 3H) ； MS (ES+) m/z 463.3 (M + 1). 128409 -239 - 200836743 實例126 3-丁基-2-[4-(四氫峨略-3-基胺基）苯基 &gt;奎嗤琳-4(3H)_酮鹽酸鹽 之合成2-(4-Bromophenyl)-3-butyl p-quineline _4(3H)-one (0.215 g, 0.62 mmol), 1-Boc-3-aminotetrahydropyrrole (0.173 g, Add 0.93 millimolar) and 2,2,-bis(diphenylphosphine)-1, hydrazine-hydrazine in toluene (15 ml) in a stirred solution, add two ginseng (diphenylmethyleneacetone) ( 0.045 g, 〇·〇 5 mmoles, followed by the addition of second-butanol (0.179 g, 1.86 mmol). The mixture was mixed for 18 hours at i 〇〇 °c. The mixture was filtered through a pad of celite and concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate / hexane, 1/2) to give 3-(4-(3-butyl </RTI> </RTI> </RTI> <RTIgt; Phenylamino)tetrahydropyridin-1-carboxylic acid tert-butyl ester (〇_250 g, 87%): 1H NMR (300 MHz, CDC13) 5 8.32-8.26 (m, 1H), 7.75-7.66 (m, 2H), 7.49-7.41 (m, 1H), 7·35 (d, J = 8.5 Hz, 2H), 6.67 (d, J = 8·5 Hz, 2H), 4.18-3.95 (m, 4H) ), 3.83-3.61 (m, 1H), 3.56-3.39 (m, 2H), 3.37-3.17 (m, 1H), 2.30-2.14 (m, 1H), 2·0 (Μ·82 (m, 1H) , 1.68-1.53 (m, 2H), 1.46 (s, 9H), 1.28] .11 (m, 2H), 0.78 (t5 J = 7.0 Hz, 3H) ; MS (ES+) m/z 463.3 (M + 1 128409 -239 - 200836743 Example 126 Synthesis of 3-butyl-2-[4-(tetrahydroindol-3-ylamino)phenyl&gt; quetialine-4(3H)-one hydrochloride

於3-(4-(3-丁基-4-酮基-3,4-二氫喹唑啉·2-基）苯基胺基）四氫 吡咯小羧酸第三-丁酯（〇_18克，0.39毫莫耳）在甲醇中之經攪 拌溶液内，添加鹽酸鹽溶液（2毫升，4Μ，在二氧陸圜中， 7.8毫莫耳）。將混合物於環境溫度下攪拌五小時。在真空 下移除溶劑及過量氯化氫。將殘留物以甲醇與醚研製，獲 得3-丁基-2-[4-(四氫吡咯-3-基胺基）苯基;μ奎唑啉_4(3Η)_酮鹽酸 鹽（0.16 克，87%)，為白色固體：iH NMR (300 MHz，DMSO-d6) 5 9.66 (br s，2H)，8.20 (d，J = 7·9 Hz，1H)，7.96 (t，J = 7.6 Hz，1H)，7.87 (d，J = 7.9 Hz，1H)，7.67 (t，J = 7.6 Hz，1H)，7.51 (d，J = 8·5 Hz，2H)，6.80 (d，J = 8·5 Hz，2H)，4.20 (br s，1H)，3.95 (t，J = 7.0 Hz，2H)，3.52-3.14 (m， 3H)，3.13-2.97 (m，1H)，2.30-2.10 (m，1H)，1.97-1.80 (m，1H)，1.65-1.45 (m，2H)，1.20-1.01 (m，2H)，0.71 (t，J = 7·0 Hz，3H) ; 13 C NMR (75 MHz， DMSO-d6) (5 160.4, 159.9, 150.8, 140.1，136.4, 130.8, 128.8, 127.4, 121.7, 119.3, 116.4, 112.3, 51.7, 49.6, 46.7, 43_8, 30.7, 29.9, 19.8, 13.8 ; MS (ES+) m/z 363.3 (M + 1). 實例127 (R)-3-(4_(2-丁基-4-酮基喹唑啉·3(4Η)-基）苯基胺基）四氫吡咯-1- 羧酸第三-丁酷之合成 128409 -240- 2008367433-(4-(3-butyl-4-keto-3,4-dihydroquinazoline-2-yl)phenylamino)tetrahydropyrrolecarboxylic acid tert-butyl ester (〇_ 18 g, 0.39 mmol), a solution of the hydrochloride salt (2 ml, 4 Torr in dioxin, 7.8 mmol) in a stirred solution in methanol. The mixture was stirred at ambient temperature for five hours. The solvent and excess hydrogen chloride were removed under vacuum. The residue was triturated with methanol and ether to give 3-butyl-2-[4-(tetrahydropyrrol-3-ylamino)phenyl; </RTI> </RTI> </RTI> <RTIgt;克, 87%) as a white solid: iH NMR (300 MHz, DMSO-d6) 5 9.66 (br s, 2H), 8.20 (d, J = 7·9 Hz, 1H), 7.96 (t, J = 7.6 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 7.6 Hz, 1H), 7.51 (d, J = 8·5 Hz, 2H), 6.80 (d, J = 8 · 5 Hz, 2H), 4.20 (br s, 1H), 3.95 (t, J = 7.0 Hz, 2H), 3.52-3.14 (m, 3H), 3.13 - 2.97 (m, 1H), 2.30-2.10 (m ,1H),1.97-1.80 (m,1H),1.65-1.45 (m,2H),1.20-1.01 (m,2H),0.71 (t,J = 7·0 Hz,3H) ; 13 C NMR (75 MHz, DMSO-d6) (5 160.4, 159.9, 150.8, 140.1, 136.4, 130.8, 128.8, 127.4, 121.7, 119.3, 116.4, 112.3, 51.7, 49.6, 46.7, 43_8, 30.7, 29.9, 19.8, 13.8 ; MS ( ES+) m/z 363.3 (M + 1). Example 127 (R)-3-(4_(2-butyl-4-ketoquinazoline·3(4Η)-yl)phenylamino)tetrahydro Pyrrole-1-carboxylic acid third-butyl synthesis128409 -240- 200836743

按照如實例86中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）-2-丁基喹唑啉_4(3H)_酮置換3-(4_溴基_2•氯苯 基）-2丁基4唾啉_4(3H)_酮，及（R)-3_胺基四氫吡咯小羧酸第三 -丁醋置換嗎福琳，獲得（r)_3_(4_(2_丁基冰酮基喳唑啉_3(4H)_ 基）苯基胺基）四氫吡咯小羧酸第三_ 丁酯（66%)，為無色固 體：熔點 200-202°C ; 1H NMR (300 MHz，DMSO-d6) 5 8.04 (d，卜 7.8 Hz，1H)，7.80-7.74 (m，1H)，7.61 (d，J = 8.7 Hz，1H)，7.48-7.42 (m，1H)， 7.03 (d，J = 8.7 Hz，2H)，6.66 (d，J = 8·7 Hz，2H)，6.17 (d，J = 6.3 Hz，1H)， 4.00-3.96 (m，1H)，3.56-3.50 (m，1H)，3.43-3.30 (m，2H)，3.12-3.09 (m， 1H)，2.34 (t，J = 7_5 Hz，2H)，2.13-2.07 (m，1H)，1.81-1.77 (m，1H)， 1.61-1.51 (m，2H)，1.37-1.36 (m，9H)，1.24-1.11 (m，2H)，0.74 (t，J = 7.2Inconsistent changes were made according to the procedure described in Example 86, using 3-(4-bromophenyl)-2-butylquinazoline-4(3H)-one to replace 3-(4-bromo) 2 • chlorophenyl)-2 butyl 4 sinoline _4(3H) ketone, and (R)-3_aminotetrahydropyrrole small carboxylic acid third-butyric acid replacement whallin, obtained (r) _3_(4_(2_butylsuccinyloxazoline-3(4H)-yl)phenylamino)tetrahydropyrrole small carboxylic acid tert-butyl ester (66%), colorless solid: melting point 200- 202 ° C ; 1H NMR (300 MHz, DMSO-d6) 5 8.04 (d, 7.8 Hz, 1H), 7.80-7.74 (m, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.48-7.42 (m,1H), 7.03 (d, J = 8.7 Hz, 2H), 6.66 (d, J = 8·7 Hz, 2H), 6.17 (d, J = 6.3 Hz, 1H), 4.00-3.96 (m, 1H), 3.56-3.50 (m, 1H), 3.43-3.30 (m, 2H), 3.12-3.09 (m, 1H), 2.34 (t, J = 7_5 Hz, 2H), 2.13-2.07 (m, 1H) ,1.81-1.77 (m,1H), 1.61-1.51 (m,2H),1.37-1.36 (m,9H),1.24-1.11 (m,2H),0.74 (t,J = 7.2

Hz5 3H) ； MS (ES+) m/z 463.2 (M + 1). 實例128 (R)_2_丁基-3-(4_(四氫吡咯基胺基）苯基）峻唑啉_4(3H)屬鹽酸 鹽水合物之合成Hz5 3H) ; MS (ES+) m/z 463.2 (M + 1). Example 128 (R)_2_butyl-3-(4_(tetrahydropyrrolylamino)phenyl) thiazoline _4 (3H ) is a synthesis of hydrochloric acid salt hydrate

按照如實例74中所述之程序，施行無關緊要之改變，使 用（R)-3-(4-(2-丁基-4_酮基喹唑啉-3(4h)_基）苯基胺基）四氫吡咯 -1-羧酸第三-丁酯置換[2-(2_丁基-4-酮基峻唑琳-3(4H)-基）乙基] 胺基甲酸第三-丁醋，獲得（R)_2-丁基各(4-(四氫吡咯-3-基胺基） 128409 -241 - 200836743 苯基）p奎嗤p林-4(3H)-酮鹽酸鹽水合物（92%)，為無色固體：熔 點 159-162°C ; 1 H NMR (300 MHz, CD3 OD) 5 8.31 (d，J = 0·9 Hz，1H)， 8.07 (dt，J = 8.4, 1·2 Hz，1H)，7.87 (d，J = 8.1 Hz，1H)，7.81-7.76 (m，1H)， 7.32-7.29 (m? 2H)5 6.97-6.94 (m? 2H)? 4.39-4.32 (m? 1H)3 3.64-3.42 (m5 3H)，3.36-3.35 (m，1H)，2.87-2.82 (m5 2H)，2.50-2.38 (m，1H)，2.21-2.11 (m，1H)，1.75-1.65 (m，2H)，1.38-1.26 (m，2H)，0.82 (t，J = 7·4 Hz，3H); 13C NMR (75 MHz，CD3OD) 5 166.7, 160.8, 149.8, 138.2, 137.9, 130.5, 130.2, 129.2, 125.1，120.5, 120.0, 115_3, 115.0, 53.7, 51.3, 45.5, 34.2, 31.5, 30.4, 23.4, 13.5 ； MS (ES+) m/z 363.2 (M + 1). 實例129 (S)-3-(4-(2-丁基-4-酮基p奎唾p林-3(4H)-基）苯基胺基）四氫说π各-μ 羧酸第三-丁 S旨之合成Inconsistent changes were made according to the procedure described in Example 74 using (R)-3-(4-(2-butyl-4-ketoquinazolin-3(4h)-yl)phenylamine Tertiary-tetrahydropyrrole-1-carboxylic acid tert-butyl ester replacement [2-(2-butyl-4-keto-trendazolin-3(4H)-yl)ethyl]carbamic acid tert-butyl Vinegar, (R) 2 -butyl each (4-(tetrahydropyrrol-3-ylamino) 128409 -241 - 200836743 phenyl)p-quine p-lin-4(3H)-one hydrochloride hydrate ( 92%), as colorless solid: mp 159-162 ° C; 1 H NMR (300 MHz, CD3 OD) 5 8.31 (d, J = 0·9 Hz, 1H), 8.07 (dt, J = 8.4, 1· 2 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.81-7.76 (m, 1H), 7.32-7.29 (m? 2H)5 6.97-6.94 (m? 2H)? 4.39-4.32 (m 1H)3 3.64-3.42 (m5 3H), 3.36-3.35 (m, 1H), 2.87-2.82 (m5 2H), 2.50-2.38 (m, 1H), 2.21-2.11 (m, 1H), 1.75-1.65 (m, 2H), 1.38-1.26 (m, 2H), 0.82 (t, J = 7·4 Hz, 3H); 13C NMR (75 MHz, CD3OD) 5 166.7, 160.8, 149.8, 138.2, 137.9, 130.5, 130.2, 129.2, 125.1, 120.5, 120.0, 115_3, 115.0, 53.7, 51.3, 45.5, 34.2, 31.5, 30.4, 23.4, 13.5 ; MS (ES+) m/z 363 .2 (M + 1). Example 129 (S)-3-(4-(2-butyl-4-keto-p-pyrene-p-lin-3(4H)-yl)phenylamino)tetrahydro Synthesis of π-di-carboxylic acid third-butadiene

按照如實例87中所述之程序，施行無關緊要之改變，使 用3-(4-溴苯基）_2_ 丁基喹唑啉-4(3H)-酮置換3-(4·溴基-2_氯苯 基）-2-丁基喹唑啉-4(3H)-酮，及（S)-3-胺基四氫吡咯-1-羧酸第三 -丁酯置換嗎福琳，獲得（S)_3-(4-(2-丁基-4-酮基喳唑# -3(4H)-基）苯基胺基）四氫吡咯-1-羧酸第三-丁酯（51%) : 1 η NMR (300 MHz，CDC13) 5 8·29_8·23 (m，1Η)，7.78-7.66 (m，2Η)，7.49-7.39 (m，1Η)， 7.03 (d，J = 8.7 Hz，2H)，6.71 (d，J = 8·7 Hz，2H)，4.18-3.92 (m，2H)， 3.82-3.65 (m，1H)，3.59-3.42 (m，2H)，3.38-3.20 (m，1H)，2.60-2.37 (m， 2H)，2.30-2.14 (m，1H)，2.03-1.85 (m，1H)，1.75-1.56 (m，2H)，1.48 (s，9H)， 128409 .242- 200836743 1.34-1.19 (m，2H)，0.82 (t，J = 7·2 Hz，3H) ; MS (ES+) m/z 463.3 (Μ + 1)· 實例130 (S)-2-丁基各(4_(四氫吡咯各基胺基）苯基 &gt;奎唑啉_4(3H&gt;酮鹽酸 鹽之合成Inconsistent changes were made according to the procedure described in Example 87, using 3-(4-bromophenyl)_2-butylquinazolin-4(3H)-one to replace 3-(4.bromo-2) Chlorophenyl)-2-butylquinazoline-4(3H)-one, and (S)-3-aminotetrahydropyrrole-1-carboxylic acid tert-butyl ester substitution of whallin, obtained (S ) 3-(4-(2-butyl-4-ketocarbazole #-3(4H)-yl)phenylamino)tetrahydropyrrole-1-carboxylic acid tert-butyl ester (51%): 1 η NMR (300 MHz, CDC13) 5 8·29_8·23 (m, 1Η), 7.78-7.66 (m, 2Η), 7.49-7.39 (m, 1Η), 7.03 (d, J = 8.7 Hz, 2H) , 6.71 (d, J = 8·7 Hz, 2H), 4.18-3.92 (m, 2H), 3.82-3.65 (m, 1H), 3.59-3.42 (m, 2H), 3.38-3.20 (m, 1H) , 2.60-2.37 (m, 2H), 2.30-2.14 (m, 1H), 2.03-1.85 (m, 1H), 1.75-1.56 (m, 2H), 1.48 (s, 9H), 128409 .242- 200836743 1.34 -1.19 (m, 2H), 0.82 (t, J = 7·2 Hz, 3H); MS (ES+) m/z 463.3 (Μ + 1)· Example 130 (S)-2-butyl each (4_( Synthesis of tetrahydropyrroleylamino)phenyl&gt; quinazoline-4 (3H&gt; ketone hydrochloride

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3HCI 使（S)-3-(4-(2-丁基冰酮基碛唑啉·3(4Η)_基）苯基胺基）四氫吡 咯-1-羧酸第三-丁酯（1.66克，3.59毫莫耳）溶於甲醇中，使其 以氣態氣化氫飽和。於環境溫度下二十四小時後，使溶劑 在真空中蒸發至乾涸。將殘留物以己烷研製，獲得⑸-丁 基-3-(4-(四氫吡咯-3-基胺基）苯基）喹唑啉_4(3Η)_酮鹽酸鹽（2.03 克，96%): 4 NMR (300 MHz，CD3OD) 5 8.22-8.16 (m，1Η)，7.99-7.91 (m，1H)，7.79-7.74 (m，1H)，7·70_7·62 (m，1H)，7·23_7·11 (m，2H)， 6.87-6.76 (m，2H)，4.30-4.16 (m，1H)，3.53-3.21 (m，3H)，2.79-2.65 (m， 2H)，2.39-2.23 (m，1H)，2.12-1.95 (m，1H)，1.66-1.49 (m，2H)，1.28-1.12 (m，2H)，0.70 (t，J = 7.3 Hz，3H) ; 13 C NMR (75 MHz，CD3 OD) 5 166.7, 160.8, 149.2, 138.2, 137.9, 130.5, 130·2, 129.1，125.6, 120.4, 120.0, 115.7, 115.5, 54.0, 51.1，45.5, 34.2, 31.3, 30.4, 23.4, 13.5 ; MS (ES+) m/z 363.2 (M + 1). 實例131 以如上述之類似方式，利用經適當取代之起始物質，製 成下列本發明化合物： 2-胺基苯甲酸4-(2-丁基冬酮基喳唑啉_3(4H)_基）苯酯； 128409 •243 - 200836743 2-[(l-甲氧基亞戊基）胺基]苯甲酸4-(2-丁基-4-酮基嗅唑琳 -3(4H)-基）苯酯； (1Ζ)-Ν-[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]戍亞胺酸甲_ ; 4-(2-丁基_4_酮基喹唑啉-3(4H)-基）苯甲酸； 2· 丁基-3-(2-硫酮基-2,3-二氫-1H-苯并咪唑-5-基 &gt;奎唑啉-4(3扣 酮； 2-丁基-3-(2,3-二髮基丙基）ρ奎唾琳_4(3Η)-_ ; 2- 丁基-3-(1-經基-1，2-二氫ρ比唆-4-基 &gt;奎唾琳-4(3Η)-酮； 3- (4-嗎福啉-4-基苯基）-2-{3-[3-(三氟甲基）苯氧基;|苯基奎唑啉 _4(3Η)-酮； 341-(2-.基-3-本氧基丙基）六氫说咬·4_基]4嗤琳_4(犯)__ ;及 Ν-[4-(2-丁基-4-酮基喳唑啉_3(4Η&gt;基）苯基](甲磺醯基）甲燒 石黃酿胺。 生物學檢測 於此項技藝中已知各種技術，以測試本發明化合物 性。為使本文中所述之發明可更充分地被瞭解，故提出下 述生物學檢測。應明瞭的是，此等實例僅供說明目的用， 而非欲被解釋為以任何方式限制本發明。 生物學實例1 脈流入量檢測（活體外檢測） 此實例係說明活體外檢測，用於測試與剖析針對安定地 表現於無論是内源或重組來源之細胞中之人類或大白鼠鈉 通道之試劑。此檢測亦可用於測定鈉通道阻斷化合物之 IC_50。此檢測係以胍通量檢測為基礎，其係等 128409 -244- 200836743 人&quot;Med (1998)，41(17) : 3298-302 所描述。 脈流入量檢測為放射示縱劑通量檢測，用以測定納通道 在高通過量微板為基礎之格式中之離子通量活性。此檢測 係利用14C-胍鹽酸鹽，且併用各種已知鈉通道調制劑，以 檢測試劑之功效。功效係藉由計算測得。選擇性係經 由將化合物對於吾人感興趣通道之功效與其抵抗其他鈉通 道之功效作比較而測得（亦稱為”選擇性剖析”）。 各試劑係針對表現吾人感興趣通道之細胞進行檢測。電 壓選通鈉通道係為無論是TTX敏感性或不敏感性。當評估 吾人感興趣通道之活性時，當其駐留在具有其他鈉通道之 /心ό群木中日守’此性質係為有用的。下表1係摘錄可於 存在或不存在下，用於筛檢某些通道活性之細胞系。 表1 細胞系 mRNA表現 功能性特徵鑒定 CHO-K1 (中國大 頰鼠卵巢；所建 議之宿主細胞 系）ATTC收受 號碼CCL-61 • Navl·4表現已藉由 RT-PCR証實 •無其他Nav表現被 檢出 '— •於[14C]胍流入量上 之18-20倍增加，係 使用TTX完全被阻 斷(Nav1.4 為 TTX 敏 感性通道） L6 (大白鼠肌胚 細胞）ATTC號 碼 CRL-1458 • Navl.4與1·5之表現 •於[14C]胍流入量上 之10-15倍增加，僅 部份被TTX阻斷 (Nav1.5 為 TTX 抗藥 性） 128409 -245 · 200836743 SH-SY5Y (人類 神經胚細胞瘤） ATTC號碼 CRL-2266 •已發表之Nav1.9與 Nav 1.7 表現（Blum 等人） •於[14C]胍流入量 上，高於背景之 10-16倍增加。 •被TTX部份阻斷 (Nav1.9 為 TTX 抗藥 性） SK-N-BE2C (人 類神經胚細胞 瘤細胞系ATCC 號碼 CRL-2268) • Nav 1.8之表現 • BE2C細胞以合成除 蟲菊酯類之刺激會 造成[14C]胍流入量 上高於背景之6倍 增加。 • TTX部份阻斷流入 量（Nav1.8 為 TTX 抗 藥性） PC12 (大白鼠親 鉻細胞瘤） ATTC號碼 CRL-1721 • Nav 1·2之表現 •於[14C]胍流入量上 之8-12-倍增加，係使 用TTX完全被阻斷 (Nav1.2 為 TTX 敏感 性通道） 亦可採用表現此等鈉通道之重組細胞。重組細胞之無性 繁殖與繁殖係為熟諳此藝者所已知（參閱，例如Klugbauer，N 等人，似必〇7：(1995)，14(6):1084-90;與1^^化，（：.等人，#,經元 (2002)，34，第 877-884 頁）。 表現吾人感興趣通道之細胞，係根據供應商，或在重組 細胞之情況中，於選擇性生長培養基譬如G418 (Gibco/ Invitrogen)存在下生長。使細胞以酵素溶液（IX)胰蛋白酶 /EDTA (Gibco/Invitrogen)自培養皿分離，並使用血球計（Neubauer) 分析密度與存活力。將已分離之細胞洗滌且再懸浮於其培 養基中，然後覆蓋於閃爍板（Scintiplate)(Beckman Coulter公司） 中（大約1〇〇,〇〇〇個細胞/井），並於37°C下/5% C02下培養20-24 128409 -246- 200836743 小時。在以低鈉HEPES-緩衝之鹽水溶液（LNHBSS) (150 mM氯 化膽驗，20 nM HEPES (Sigma)，1 mM 氯化鈣，5 mM 氯化鉀，1 mM 氯化鎂，10 mM葡萄糖）廣泛洗滌後，將以LNHBSS稀釋之藥 劑添加至各井中（可使用不同濃度之試劑）。活化/放射性標 識混合物含有烏頭素（Sigma)與14 C-脈鹽酸鹽（ARC)。 在將細胞裝填試劑與活化/放射性標識混合物後，將閃爍 板於環境溫度下培養。在培養之後，將閃爍板廣泛地以補 充脈（Sigma)之LNHBSS洗滌。使閃爍板乾燥，然後使用Wallac MicroBeta Trilux (Perkin-Elmer生命科學）計數。試劑阻斷鈉通道 活性之能力，係經由比較存在於表現不同鈉通道之細胞内 部之14C-胍量而測得。以此數據為基礎，多種計算值，如 洋述於本專利說明書中別處，可用以測定試劑對特定鈉通 道是否具選擇性。 試劑對特定鈉通道之IC_50值可使用上述一般方法測定。 IC-50可使用3、8、1〇、12或16點曲線，以兩份複製或三份 複製測定，具有起始濃度為卜5或⑺顺，連續性地以達到 亞笔微莫耳〉辰度、宅微莫耳濃度及低微莫耳濃度範圍之最 後濃度稀釋。典型上，試劑之中點濃度係設定於_下， 而係應用大於或小於半稀釋液之連續濃度（例如〇·5卓；^ ” 〇·25 //Μ ’ 10 _與〇125 _ ; 2〇靡等）。以〇曲線係使 多數汁异術杈式或s形劑量_回應模式計算（吻合= (A+((B-A)/(l+((c/x，D)))) 〇 數k擇f生、選擇性之因數或選擇性之倍數，係經由將 、鈉通道之IC_5G值除以參考鈉通道例如~ 15，計算而 128409 -247- 200836743 得。 «明之代表性化合物’當在上述檢測中使用會表現納 通道之已知細胞系測試時，係展現如下文表2中所提出之 Κ^(ηΜ)活性含量，其中”A”係指IC5G活性含量從工疆至1〇 nM，B係指IC5 〇活性含量從1〇 nM至1〇〇 nM，&quot;c，，係指冗5 〇 活性含量從100 nM至1000 nM，及”D”係指IC5()活性含量等於 或大於1000 nM。表2中所提供之實例數字係相應於本文之 實例： 表23HCI (S)-3-(4-(2-butylecrocarbyloxazoline·3(4Η)-yl)phenylamino)tetrahydropyrrole-1-carboxylic acid tert-butyl ester (1.66 Grams, 3.59 mmol are dissolved in methanol to make it saturated with gaseous hydrogenation. After twenty-four hours at ambient temperature, the solvent was evaporated to dryness in vacuo. The residue was triturated with hexane to give (5)-butyl-3-(4-(tetrahydropyrrol-3-ylamino)phenyl) quinazoline <RTI ID=0.0>(3 </RTI> </RTI> <RTIgt; 96%): 4 NMR (300 MHz, CD3OD) 5 8.22-8.16 (m, 1 Η), 7.99-7.91 (m, 1H), 7.79-7.74 (m, 1H), 7·70_7·62 (m, 1H) ,7·23_7·11 (m,2H), 6.87-6.76 (m,2H), 4.30-4.16 (m,1H),3.53-3.21 (m,3H),2.79-2.65 (m, 2H), 2.39- 2.23 (m, 1H), 2.12-1.95 (m, 1H), 1.66-1.49 (m, 2H), 1.28-1.12 (m, 2H), 0.70 (t, J = 7.3 Hz, 3H); 13 C NMR ( 75 MHz, CD3 OD) 5 166.7, 160.8, 149.2, 138.2, 137.9, 130.5, 130·2, 129.1, 125.6, 120.4, 120.0, 115.7, 115.5, 54.0, 51.1, 45.5, 34.2, 31.3, 30.4, 23.4, 13.5 MS (ES+) m/z 363.2 (M + 1). </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; -butylbutanyloxazoline_3(4H)-yl)phenyl ester; 128409 •243 - 200836743 2-[(l-methoxypentamethylene)amino]benzoic acid 4-(2-butyl 4-keto tyrosazoline-3(4H)-yl)phenyl ester; (1Ζ)-Ν-[4-(2-butyl 4-ketooxazoline-3(4H)-yl)phenyl]decyl imine A; 4-(2-butyl-4-ylketoquinolin-3(4H)-yl)benzene Formic acid; 2·butyl-3-(2-thioketo-2,3-dihydro-1H-benzimidazol-5-yl>gt; quinazoline-4 (3 ketone; 2-butyl-3 -(2,3-dipropylpropyl) ρ 奎 琳 _ 4 4 4 4 4 4 4 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- &gt;Querazine-4(3Η)-one;3-(4-morpholin-4-ylphenyl)-2-{3-[3-(trifluoromethyl)phenoxy;奎 oxazoline _4(3Η)-one; 341-(2-.yl-3- phenoxypropyl) hexahydro narrate 4_yl]4嗤琳_4(criminal)__ ; and Ν-[ 4-(2-Butyl-4-ketooxazoline-3(4Η&gt;yl)phenyl](methanesulfonyl)methanthroate. Biological Detection Various techniques are known in the art to test the compounds of the present invention. In order for the invention described herein to be more fully understood, the following biological assays are proposed. It is to be understood that the examples are for illustrative purposes only and are not intended to be construed as limiting the invention in any manner. Biological Example 1 Pulse Influx Detection (In Vitro Assay) This example illustrates in vitro assays for testing and profiling reagents for human or rat sodium channels that are stably present in cells of either endogenous or recombinant origin. . This test can also be used to determine the IC50 of the sodium channel blocking compound. This test is based on 胍 flux detection and is described by 128409-244-200836743 People &quot;Med (1998), 41(17): 3298-302. Pulse influx was detected as a radiotropic flux assay to determine the ion flux activity of the nanochannel in a high throughput microplate-based format. This assay uses 14C-guanidine hydrochloride and uses various known sodium channel modulators to test the efficacy of the reagents. Efficacy is measured by calculation. Selectivity is measured by comparing the efficacy of the compound to the channel of interest to us against its efficacy against other sodium channels (also known as "selective profiling"). Each reagent is tested against cells that express the channels of interest to us. The voltage-selected sodium channel is either TTX sensitive or insensitive. When assessing the activity of a channel of interest to us, it is useful when it resides in a group of other sodium channels. Table 1 below is an excerpt from a cell line that can be used to screen for the activity of certain channels in the presence or absence. Table 1 Cell line mRNA performance functional characteristics Identification CHO-K1 (Chinese big cheek ovary; recommended host cell line) ATTC acceptance number CCL-61 • Navl·4 performance has been confirmed by RT-PCR • No other Nav performance It was detected that - 18 - 20-fold increase in [14C] 胍 influx was completely blocked by TTX (Nav1.4 is TTX-sensitive channel) L6 (Large mouse blast) ATTC number CRL- 1458 • Performance of Navl.4 and 1-5 • 10-15 fold increase in [14C] 胍 influx, only partially blocked by TTX (Nav1.5 is TTX resistant) 128409 -245 · 200836743 SH- SY5Y (Human Neuroblastoma) ATTC Number CRL-2266 • Published Nav1.9 and Nav 1.7 performance (Blum et al.) • 10-16 fold increase in [14C] 胍 influx. • Blocked by TTX (Nav1.9 is TTX resistant) SK-N-BE2C (Human neuroblastoma cell line ATCC number CRL-2268) • Performance of Nav 1.8 • Pyrethroids in BE2C cells The stimulus will cause a [14C] 胍 inflow that is 6 times higher than the background. • TTX partial block influx (Nav1.8 is TTX resistant) PC12 (Chromosome chromosomal cell) ATTC number CRL-1721 • Performance of Nav 1·2 • 8 in [14C] 胍 influx A 12-fold increase is completely blocked by the use of TTX (Nav1.2 is a TTX-sensitive channel) and recombinant cells expressing these sodium channels can also be used. The asexual reproduction and propagation of recombinant cells is known to those skilled in the art (see, for example, Klugbauer, N et al., et al., 7: (1995), 14(6): 1084-90; , (:. et al., #, 经元(2002), 34, pp. 877-884). Cells that express the channels of interest to us, depending on the supplier, or in the case of recombinant cells, in selective growth media For example, growth is carried out in the presence of G418 (Gibco/Invitrogen). The cells are separated from the culture dish by enzyme solution (IX) trypsin/EDTA (Gibco/Invitrogen) and the density and viability are analyzed using a hemocytometer (Neubauer). The cells were washed and resuspended in their medium and then covered in a scintillation plate (Beckman Coulter) (approximately 1 inch, one cell/well) and at 37 ° C / 5% C02 Culture 20-24 128409 -246-200836743 hours. In low sodium HEPES-buffered saline solution (LNHBSS) (150 mM chlorination test, 20 nM HEPES (Sigma), 1 mM calcium chloride, 5 mM potassium chloride , 1 mM magnesium chloride, 10 mM glucose) After extensive washing, the drug diluted with LNHBSS was added to each well. (Different concentrations of reagents can be used.) The activation/radioactive labeling mixture contains aconitin (Sigma) and 14 C-hypoflurane (ARC). After mixing the cells with the activation/radioactive labeling, the scintillation plate is placed in the environment. Culture at temperature. After incubation, the scintillation plates were extensively washed with LNHBSS supplemented with Sigma (Sigma). The scintillation plates were dried and then counted using Wallac MicroBeta Trilux (Perkin-Elmer Life Sciences). The ability of the reagent to block sodium channel activity , measured by comparing the amount of 14C-胍 present in cells that exhibit different sodium channels. Based on this data, various calculated values, such as elsewhere in this patent specification, can be used to determine reagents for specific sodium channels. Whether it is selective. The IC_50 value of the reagent for a specific sodium channel can be determined using the above general method. IC-50 can be measured in two copies or three copies using a 3, 8, 1 〇, 12 or 16-point curve. The initial concentration is 5 or (7) cis, and is continuously diluted to reach the final concentration of the sub-micro-mole, the house micro-mole concentration and the low micro-mole concentration range. The point concentration of the reagent is set to _, and the application is greater or less than the continuous concentration of the semi-dilution solution (for example, 〇·5卓; ^ 〇 25·25 //Μ ' 10 _ and 〇 125 _ ; 2〇靡Etc.) The 〇 curve is used to calculate the majority of the juice or sigmoid dose _ response mode (always = (A + ((BA) / (l + ((c / x, D))))) The factor of birth, selectivity, or selectivity is calculated by dividing the IC_5G value of the sodium channel by the reference sodium channel, for example, ~ 15, and 128409 -247-200836743. "Representative compound of the formula" when tested in a known cell line which exhibits a nanochannel in the above assay, exhibits an activity of Κ^(ηΜ) as set forth in Table 2 below, where "A" refers to IC5G activity. The content ranges from labor to 1〇nM, and B refers to IC5 〇 active content from 1〇nM to 1〇〇nM,&quot;c, which means redundant 5 〇 active content from 100 nM to 1000 nM, and “D” system Refers to an IC5() active content equal to or greater than 1000 nM. The example numbers provided in Table 2 correspond to the examples in this paper: Table 2

實例 編號 化合物名稱 IC5〇 活性含量 1 丁基-3_(4-甲氧苯基）π奎唾琳_4(3H)·酮 D 2 3-(3-胺基苯基）-2-丁基4唾琳-4(3H)·酮 D 3 2-丁基-3-(4-經苯基&gt;套4淋_4(311)-酮 C 4 4-(2-丁基-4-g同基p奎唾p林-3(4H)-基）苯甲酸胺 D 5 二鼠1甲烧石頁酸4-(2-丁基-4-嗣基P奎σ坐P林 -3(4Η)-基）苯酯 D 7 3-(4-胺基苯基）-2-丁基喹唑啉_4(3Η)-酮 B 8 5-(2-丁基-4-酮基喳唑啉-3(4Η)-基）-2,3-二氫-1Η-吲哚-1-羧酸第三-丁酯 D 9 2-丁基-3·(2,3-二氫-1Η_啕哚-5-基）喳唑啉 -4(3Η)·酮 D 10 4-(2-丁基-4-酮基ρ奎唆淋-3(4Η)-基）苯績醯胺 D 11 4·(2-丁基-4·酮基喹唑啉·3(4Η)-基） 苯甲酸甲酯 D 13 2-丁基哚-5-基）喳唑啉-4(3Η)-酮 D 16 3-(4-胺基苯基）-2-丙基喹唑啉-4(3Η)-酮 B 18 3-(4-胺基苯基）-2-乙基喹唑啉-4(3Η)-酮 C 128409 -248 - 200836743Example No. Compound Name IC5〇Active Content 1 Butyl-3_(4-methoxyphenyl)π奎奎琳_4(3H)·ketone D 2 3-(3-Aminophenyl)-2-butyl 4 Salivin-4(3H)·ketone D 3 2-butyl-3-(4-Phenyl)&gt; Set 4 _4(311)-ketone C 4 4-(2-butyl-4-g基普奎唾p林-3(4H)-yl)benzoic acid amine D 5 two mice 1 a burnt stone acid 4-(2-butyl-4-mercapto P quinine sitting P Lin-3 (4 Η) -yl)phenyl ester D 7 3-(4-aminophenyl)-2-butylquinazoline-4(3Η)-one B 8 5-(2-butyl-4-ketooxazoline- 3(4Η)-yl)-2,3-dihydro-1Η-fluorene-1-carboxylic acid tert-butyl ester D 9 2-butyl-3·(2,3-dihydro-1Η_啕哚-5-yl)oxazoline-4(3Η)·ketone D 10 4-(2-butyl-4-keto-p-quine-indole-3(4Η)-yl)benzene phthalamide D 11 4·( 2-butyl-4·ketoquinazoline·3(4Η)-yl) methyl benzoate D 13 2-butylindole-5-yl)oxazoline-4(3Η)-one D 16 3- (4-Aminophenyl)-2-propylquinazoline-4(3Η)-one B 18 3-(4-Aminophenyl)-2-ethylquinazoline-4(3Η)-one C 128409 -248 - 200836743

實例 編號 化合物名稱 iQ〇 活性含量 19 3-(4-溴苯基）-2-丁基喹唑啉-4(3H)-酮 D 21 2-丁基-3-(2-酮基-2,3-二氫-1，3-苯并嘮唑-6-基）喹唑啉-4(3H)-酮 D 22 3-(1Η-苯并三唑-5-基）-2-丁基喳唑啉-4(3H)-酮 D 23 5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-1Η-蚓唑 -1-羧酸第三-丁酯 D 24 2-丁基-3-(1Η-吲唑-5-基）喹唑啉-4(3H)-酮 D 25 1_[4-(2-丁基-4-酮基喹唑啉-3(4H)-基） 苯基]脲 D 26 3-(6-胺基吡啶各基）-2-丁基喹唑啉-4(3H)-酮 D 28 2_丁基各[4-(甲胺基）苯基]喹唑啉-4(3H)·酮 D 29 3-(4-胺基苯基）-2·甲基喹唾啉-4(3H)-酮 D 30 3-(3-胺基苯基&gt;2-甲基喹唑啉-4(3H)-酮 D 31 3-(4-胺基苯基）-2-戊基喹嗤啉-4(3H)-酮 B 33 3-(2-胺基苯基&gt;2-丁基喹唑啉-4(3H)-酮 D 36 1-[4-(2-丁基-4-酮基喹唑啉-3(4H)-基） 苯基]胍 D 37 2-丁基-3-(4-硝基苄基）喹唑啉-4(3H)-酮 D 38 3-(4-胺基苄基）-2-丁基喹唑啉-4(3H)-酮 D 39 1-[4-(2-丁基-4-S同基喹唑啉-3(4H)-基）苯 基]-3-氣脈 D 40 3-(4-胺基-2,5-二氯苯基）-2-丁基喳唑啉 -4(3H)-酮 D 41 3-(4-胺基-2,5-二甲基苯基）-2-丁基p奎嗤淋 -4(3H)-酉同 D 42 3-(4-胺基-2,3,5,6-四曱基苯基）-2-丁基喳唑 啉-4(3H)-酮 D 43 4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯甲月f D 128409 -249- 200836743Example No. Compound Name iQ〇 Active Content 19 3-(4-Bromophenyl)-2-butylquinazolin-4(3H)-one D 21 2-butyl-3-(2-keto-2, 3-Dihydro-1,3-benzoxazol-6-yl)quinazolin-4(3H)-one D 22 3-(1Η-benzotriazol-5-yl)-2-butylindole Oxazoline-4(3H)-one D 23 5-(2-butyl-4-ketoquinazolin-3(4H)-yl)-1Η-indazole-1-carboxylic acid tert-butyl ester D 24 2-butyl-3-(1Η-indazol-5-yl)quinazolin-4(3H)-one D 25 1_[4-(2-butyl-4-ketoquinazolin-3) 4H)-yl)phenyl]urea D 26 3-(6-aminopyridinyl)-2-butylquinazoline-4(3H)-one D 28 2-butyl each [4-(methylamine) Phenyl]quinazolin-4(3H)·ketone D 29 3-(4-aminophenyl)-2·methylquinoxalin-4(3H)-one D 30 3-(3-amine Phenylphenyl&gt;2-methylquinazolin-4(3H)-one D 31 3-(4-Aminophenyl)-2-pentylquinoxaline-4(3H)-one B 33 3- (2-Aminophenyl)&gt;2-butylquinazolin-4(3H)-one D 36 1-[4-(2-butyl-4-ketoquinazolin-3(4H)-yl Phenyl]indole D 37 2-butyl-3-(4-nitrobenzyl)quinazolin-4(3H)-one D 38 3-(4-aminobenzyl)-2-butylquin Oxazoline-4(3H)-one D 39 1-[4-(2-butyl-4-S-isoquinoquine Porphyrin-3(4H)-yl)phenyl]-3-intragas D 40 3-(4-Amino-2,5-dichlorophenyl)-2-butyloxazoline-4(3H)-one D 41 3-(4-Amino-2,5-dimethylphenyl)-2-butyl p-quinone-lead-4(3H)-酉 with D 42 3-(4-Amino-2,3 ,5,6-tetradecylphenyl)-2-butyloxazoline-4(3H)-one D 43 4-(2-butyl-4-ketooxazoline-3(4H)-yl ) Benzene month f D 128409 -249- 200836743

實例 編號 化合物名稱 IC5〇 活性含量 44 2-丁基-3巧比唆-4-基峻嗤琳-4(3H)__ D 45 2-丁基-3-(6-甲乳基^比σ定-3·基）峻唾淋_ 4(3Η)， D 46 [4-(2-丁基-4-酮基喹唾啉-3(4Η)-基）苄基] 胺基甲酸第三-丁酯 D 47 3-[4-(胺基甲基）苯基]-2-丁基喳唑啉-4(3Η)-酮 D 48 3-(1，3-苯并二氧伍圜烯-5-基）-2-丁基喹唑 啉-4(3H)-酮 D 49 3-(5-胺基奈-1_基）-2-丁基峰σ坐p林-4(3H)-酉同 D 50 2-丁基-3-(6-0同基-1，6-二鼠^σ定-3-基奎σ坐口林 -4(3 Η)-嗣 D 53 3-[4-胺基各(三氟甲基）苯基]-2-丁基喳唑啉 -4(3Η)-酮 D 55 3-[4-胺基-2-(三氟甲基）苯基]-2-丁基喹唑啉 -4(3H)-酉同 D 62 3-(4-胺基苯基）-2-丁基-6-氣基峻。坐琳_ 4(3H)-酮 C 63 3-(4-胺基苯基）-2-丁基-7-氣基峻嗤琳_ 4(3H)-酮 D 65 2-丁基-3-(4-氟苯基）喳唑啉-4(3H)-酮 D 66 2-丁基-7-硝基-3-苯基喳唑淋-4(3H)-酮 D 67 2-丁基-6-硝基-3-苯基喹唑啉-4(3H)-酮 D 68 2-丁基-3-(4-氯苯基）喳唑啉-4(3H)-酮 D 69 7-胺基-2-丁基-3-苯基邊°坐^林-4(3H)-酉同 D 70 3-(2,3-二羥基丙基）-2-甲基喹唑啉·4(3Η)_酮 D 71 6-胺基-2-丁基-3-苯基喹唑啉-4(3Η)-酮 D 72 [3-(2-丁基-4-酮基喳唑啉-3(4Η)-基）丙基] 胺基甲酸第三-丁酯 D 128409 -250 - 200836743Example No. Compound name IC5 〇 active content 44 2-butyl-3 Qiao 唆-4-基君嗤琳-4(3H)__ D 45 2-butyl-3-(6-methyllater^ ratio σ -3·基)峻唾淋_ 4(3Η), D 46 [4-(2-butyl-4-ketoquinoxalin-3(4Η)-yl)benzyl]carbamic acid tert-butyl Ester D 47 3-[4-(Aminomethyl)phenyl]-2-butyloxazoline-4(3Η)-one D 48 3-(1,3-benzodioxanthene-5 -yl)-2-butylquinazoline-4(3H)-one D 49 3-(5-Aminona-1-yl)-2-butyl peak σ sitting p-lin-4(3H)-酉D 50 2-butyl-3-(6-0-iso-l-,6-di-rhamnium sigma--3- ke sigma sigma-4 -3 3)-嗣D 53 3-[4-amino Each (trifluoromethyl)phenyl]-2-butyloxazoline-4(3Η)-one D 55 3-[4-amino-2-(trifluoromethyl)phenyl]-2-butene Alkyl quinazoline-4(3H)-indole with D 62 3-(4-aminophenyl)-2-butyl-6-gas base. Sitting _ 4(3H)-ketone C 63 3-( 4-aminophenyl)-2-butyl-7-gasyl 嗤 _ _ 4(3H)-one D 65 2-butyl-3-(4-fluorophenyl)oxazoline-4 (3H )-ketone D 66 2-butyl-7-nitro-3-phenyloxazolidine-4(3H)-one D 67 2-butyl-6-nitro-3-phenylquinazoline-4 (3H)-ketone D 68 2-butyl-3-(4-chlorobenzene )oxazoline-4(3H)-one D 69 7-Amino-2-butyl-3-phenyl side °^^^(3H)-酉同D 70 3-(2,3-二Hydroxypropyl)-2-methylquinazoline·4(3Η)-one D 71 6-Amino-2-butyl-3-phenylquinazoline-4(3Η)-one D 72 [3- (2-butyl-4-ketooxazoline-3(4Η)-yl)propyl] carbamic acid tert-butyl ester D 128409 -250 - 200836743

實例 編號 化合物名稱 ic50 活性含量 73 [2-(2·丁基-4-嗣基喹唑啉-3(4H)-基）乙基] 胺基曱酸第三-丁酯 D 74 3-(2-胺基乙基）-2-丁基喳唑啉·4(3Η)·酮二鹽 酸鹽 D 75 3-(3-胺基丙基）-2-丁基喹唑啉-4(3Η)-酮二鹽 酸鹽 D 76 2-丁基-3-(2-六氮ρ比σ定-1-基乙基）峻σ坐琳 ·4(3Η)_ 酮 D 77 3-(4-溴基-2-氟苯基）-2-丁基喹唑啉-4(3Η)-酮 D 78 2-丁基-3-(3-六氮ρ比σ定-1-基丙基）^奎°坐口林 -4(3Η)-酉同 D 79 3-(4-溴基-2-氯苯基）-2-丁基喳唑啉-4(3Η)-酮 D 80 3-[4-&gt;臭基-2-(二氣甲基）苯基]-2-丁基ρ奎吐ρ林 -4(3Η)-酉同 D 81 3-(4-溴基-2,6-二氟苯基）-2-丁基喹唑啉 -4(3H)-酮 D 82 3-(4-&gt;臭基-2-甲基苯基）-2-丁基^奎嗤p林_ 4(3H)-酮 D 83 3·(4-溴基-2,6-二甲基苯基）-2-丁基喹唑啉 -4(3H)·酉同 D 84 2-丁基-3-(3-四氫卩比洛-1-基丙基 &gt;奎吐口林 -4(3H)-酮 D 85 2-丁基-3-[2-(l-甲基四氫吡咯-2-基）乙基]喳 唾琳-4(3H)-酮 D 87 2·丁基-3-[4-嗎福啉-4-基-2-(三氟甲基）苯基] ττ奎ΰ坐琳-4(3H)-酮 D 88 2-丁基-3-(2,6-二氟-4-嗎福啉-4-基苯基）喹唑 口林-4(3H)-酉同 D 89 2-丁基-3-(2-曱基-4-嗎福啉-4-基苯基）喹唑 啉-4(3H)-酮 D 128409 -251 - 200836743Example No. Compound name ic50 Active content 73 [2-(2·butyl-4-mercaptoquinazolin-3(4H)-yl)ethyl]amino decanoic acid tert-butyl ester D 74 3-(2 -aminoethyl)-2-butyloxazoline·4(3Η)·one dihydrochloride D 75 3-(3-Aminopropyl)-2-butylquinazoline-4(3Η) -keto dihydrochloride D 76 2-butyl-3-(2-hexanitro-p-r-butyr-1-ylethyl) σσ坐琳·4(3Η)_ ketone D 77 3-(4-bromo 2-fluorophenyl)-2-butylquinazoline-4(3Η)-one D 78 2-butyl-3-(3-hexanitro-p-r-azyl-1-ylpropyl)-quine ° Stomach Lin-4(3Η)-酉同D 79 3-(4-Bromo-2-chlorophenyl)-2-butyloxazoline-4(3Η)-one D 80 3-[4- &gt;Smellyyl-2-(dimethylmethyl)phenyl]-2-butyl ρ 奎 ρ 林 -4 -4 (3Η)-酉同D 81 3-(4-bromo-2,6-difluoro Phenyl)-2-butylquinazolin-4(3H)-one D 82 3-(4-> odor-2-methylphenyl)-2-butyl^ quinone p _ 4 ( 3H)-ketone D 83 3·(4-bromo-2,6-dimethylphenyl)-2-butylquinazoline-4(3H)·酉 with D 84 2-butyl-3-( 3-tetrahydroindolebi-1-ylpropyl&gt; Kudzuulin-4(3H)-one D 85 2-butyl-3-[2-(l-methyltetrahydropyrrole-2-yl) Ethyl] 喳 琳 琳 - 4 (3H) -ketone D 87 2·butyl-3-[4-morpholino-4-yl-2-(trifluoromethyl)phenyl] ττ奎ΰ坐琳-4(3H)-one D 88 2-butyl 3-(2,6-difluoro-4-morpholine-4-ylphenyl)quinazoline-4(3H)-indole D 89 2-butyl-3-(2-indenyl) -4-morpholine-4-ylphenyl)quinazolin-4(3H)-one D 128409 -251 - 200836743

實例 編號 化合物名稱 IC5〇 活性含量 90 2-丁基各(2,6-二甲基-4-嗎福啉-4-基苯基）喹 唑啉-4(3H)-酮 D 91 2-丁基-3-(2-氣基-4-嗎福淋-4_基苯基奎。坐 淋-4(3H)-酉同 D 93 2-丁基-3-{4-[2-(苯氧基曱基）嗎福啉-4-基]苯 基}喹唑啉-4(3H)-酮 D 94 2-丁基-3·(4-{[(2,2-二曱基-1，3-二氧伍圜-4-基）曱基]胺基}苯基）峻唾淋-4(3H)-酉同 D 95 2-丁基-3-{4·[(2,3-二羥基丙基）胺基]苯基} π奎。坐琳-4(3Η)·酮 D 96 2_丁基-Η4-[(2_經基-3_苯氧基丙基）胺基]苯 基ρ奎唑淋-4(3Η)-酮 D 98 3-(4-胺基環己基）-2-丁基ρ奎嗤琳-4(3Η)-酮鹽 酸鹽 D 101 2-丁基-3-[1-(2-經基-3-苯氧基丙基）六氫υ比 啶-4-基]喹唑啉-4(3Η)-酮 D 102 3-{1-[3-(爷氧基）-2-經丙基]六氫峨。定-4-基}-2-丁基4峻琳-4(3Η)-酮 D 103 Ν-[4-(2-丁基-4-酮基ρ查唾琳-3(4Η)-基）苯基] 甲烷磺醯胺 D 104 Ν-[4_(2-丁基-4-酮基喳唑琳-3(4Η)-基）苯基] 乙酿胺 D 105 2-丁基-3-[4-(吡啶-2-基胺基）苯基]喹唑啉 -4(3Η)-酮 D 106 2-丁基_3-(4-嗎福淋-4·基苯基奎嗤琳_ 4(3Η)， C 107 3-{[4-(2-丁基-4-酮基喳唑啦_3(4Η)_基）苯基] 胺基}四氫吡咯-1_綾酸第三-丁酯 D 108 2_ 丁基-3-(4-{[2-(二甲胺基）乙基]胺基}苯基) 口套吐4 -4(3Η)-酮 D 128409 -252- 200836743 實例 編號 化合物名稱 IC5〇 活性含量 109 2-丁基_3-[4-(4·甲基六氫吡。井小基）苯基p奎 唑啉-4(3H)-酮 D 111 2_丁基-3-(4-六氮峨17定-1-基苯基）p奎σ坐p林 -4(3Η)-酮 D 113 2_丁基·3_[4-(四氫卩比略-3-基胺基）苯基]卩奎〇坐 p林-4(3H)-嗣 D 114 2-丁基-3-(4-六氯ρ比呼-1-基苯基奎u坐琳 -4(3H)-酮二鹽酸鹽 D 115 2-丁基-3-[4-(六氣ρ比σ定-3-基胺基）苯基]峻σ坐 淋-4(3 Η)-酮二鹽酸鹽 D 116 3-(4-嗎福琳-4-基苯基）-2-苯基ρ奎。坐淋-4(3H)-酮 D 131 2-胺基本甲酸4-(2-丁基-4-0¾基峻唾p林 -3(4H)-基）苯酯 D 131 2-[(1-甲氧基亞戊基）胺基]苯甲酸4-(2-丁基 -4-酮基喳唑啉·3(4Η&gt;基）苯酯 D 131 (1Ζ)-Ν-[4-(2-丁基-4-酮基 π奎唾 ρ林-3(4Η)-基）苯 基]戊亞胺酸甲酯 B 131 4-(2-丁基-4-酉同基π奎唾琳_3(4Η)_基）苯甲酸 D 131 1 2-丁基-3-(2,3-二經基丙基）ρ奎u坐琳-4(3Η)-酮 D 131 3-(5-胺基-3，4-二氫莕小基）-2-丁基p奎唾琳 -4(3H)-酮 D 131 2-丁基-3-(1-¾基-1，2-二氫p比咬-4-基）p奎唾琳 -4(3H)-酮 D 131 2·丁基-3-(6-氣基-4-嗎福琳-4-基苯基奎唾 琳-4(3H)-酉同 D 131 3-(4-嗎福啉-4-基苯基）-2-{3-[3-(三氟甲基）苯 氧基]苯基}喹唾啉-4(3H)-酮 D 131 3-[1-(2·經基-3-苯氧基丙基）六氫说σ定_4_基] 邊峻琳-4(3Η)-酮 D ----- 128409 -253 - 200836743Example No. Compound name IC5〇 Active content 90 2-butyl each (2,6-dimethyl-4-norfosolin-4-ylphenyl)quinazolin-4(3H)-one D 91 2-butyl Benzyl-3-(2-carbyl-4-?-fluofole-4-ylphenyl quinone. sitine-4(3H)-酉 with D 93 2-butyl-3-{4-[2-(benzene Oxyfluorenyl)norfosolin-4-yl]phenyl}quinazolin-4(3H)-one D 94 2-butyl-3·(4-{[(2,2-didecyl-1) ,3-dioxy-indolyl-4-yl)indolyl]amino}phenyl) sulphate-4(3H)-酉 with D 95 2-butyl-3-{4·[(2,3- Dihydroxypropyl)amino]phenyl} π quinine.Shenlin-4(3Η)·ketone D 96 2_butyl-indole 4-[(2_transyl-3-phenoxypropyl)amino] Phenyl ρ quinazolin-4(3Η)-one D 98 3-(4-Aminocyclohexyl)-2-butyl ρ 嗤 -4 -4-4(3Η)-one hydrochloride D 101 2-butyl -3-[1-(2-Phenyl-3-phenoxypropyl)hexahydrobipyridin-4-yl]quinazolin-4(3Η)-one D 102 3-{1-[3- (yloxy)-2-propyl-propyl hexahydroindole. 1,4-yl}-2-butyl 4-junolin-4(3Η)-one D 103 Ν-[4-(2-butyl- 4-keto group ρ 唾 琳 -3 -3 (4 Η)-yl) phenyl] methane sulfonamide D 104 Ν-[4_(2-butyl-4-keto oxazolin-3(4Η)-yl) Phenyl] ethylamine D 105 2-butyl-3 -[4-(pyridin-2-ylamino)phenyl]quinazolin-4(3Η)-one D 106 2-butyl_3-(4-isofolin-4-phenylphenylquinone _ 4(3Η), C 107 3-{[4-(2-butyl-4-ketocarbazolela_3(4Η)-yl)phenyl]amino}tetrahydropyrrole-1_decanoic acid Tri-butyl ester D 108 2_ butyl-3-(4-{[2-(dimethylamino)ethyl]amino}phenyl) mouth spit 4 -4(3Η)-one D 128409 -252- 200836743 Example No. Compound name IC5〇Active content 109 2-butyl_3-[4-(4·methylhexahydropyridyl. well small)phenyl p-quinazoline-4(3H)-one D 111 2_ Butyl-3-(4-hexanitropurine 17-den-1-ylphenyl)p-quinone sigma p-lin-4(3Η)-one D 113 2_butyl·3_[4-(tetrahydroanthracene -3-ylamino)phenyl]indole quinone sitting p-lin-4(3H)-嗣D 114 2-butyl-3-(4-hexachloro-p-hept-1-ylphenyl quinone -4(3H)-keto-dihydrochloride D 115 2-butyl-3-[4-(hexa-gas ρ σ -3-amino-amino)phenyl] σ 坐 坐 -4 (3 Η) - keto dihydrochloride D 116 3-(4-fofolin-4-ylphenyl)-2-phenyl ρ 奎. Sesame-4(3H)-keto D 131 2-amine basic formic acid 4-(2-butyl-4-03⁄4 base saponin-3-(4H)-yl)phenyl ester D 131 2-[(1- 4-(2-butyl-4-ketooxazoline·3(4Η&gt;yl)phenyl ester of methoxypentylene)amino]benzoic acid D 131 (1Ζ)-Ν-[4-(2- Methyl butyl-4-keto π quinegonin-3(4Η)-yl)phenyl]pentimidolate B 131 4-(2-butyl-4-oxirane π 奎奎琳_3 (4Η)_yl)benzoic acid D 131 1 2-butyl-3-(2,3-dipropylpropyl) ρ 奎u sitin-4(3Η)-ketone D 131 3-(5-amino group -3,4-dihydroindolyl)-2-butyl p-quineline-4(3H)-one D 131 2-butyl-3-(1-3⁄4yl-1,2-dihydrop ratio Bite-4-yl)p-quineline-4(3H)-one D 131 2·butyl-3-(6-carbyl-4-fofofene-4-ylphenylquinidine-4(3H )-D-D 131 3-(4-Morfosolin-4-ylphenyl)-2-{3-[3-(trifluoromethyl)phenoxy]phenyl}quinoxalin-4 (3H )-ketone D 131 3-[1-(2·Pyryl-3-phenoxypropyl)hexahydro sigma _4_yl] Bian Junlin-4(3Η)-ketone D ----- 128409 -253 - 200836743

實例 編號 化合物名稱 IC5〇 活性含量 131 N-[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯 基]-N-(甲磺醯基）甲烷磺醯胺 D 生物學實例2 電生理學檢測（活體外檢測） 將表現吾人感興趣通道之細胞在具有0.5毫克/毫升G418, +/-1% PSG與10%熱失活牛胎兒血清之DMEM生長培養基 (Gibco)中，於37°C與5% C02下培養。為了電生理學記錄，將 細胞覆蓋於10毫米培養皿上。 全細胞記錄係藉由已建立之全細胞電壓夾持方法（Bean 等人，在冷&quot;遂之|作尹），使用Axopatch 200B放大器與 Clampex軟體（Axon儀器，Union City，CA)檢驗。所有實驗係於環 境溫度下進行。使電極著火拋光至2-4 Mohm電阻，電壓誤 差與電容人為產物係個別藉由串聯電阻補償作用與電容補 償作用而被降至最低。數據係在40 kHz下獲取，及在5 kHz 下過濾。外部（浴槽）溶液包含：NaCl (140 mM)，KC1 (5 mM)， CaCl2 (2 mM)，MgCl2 (1 mM)，HEPES (10 mM)在 pH 7·4 下。内部（吸 量管）溶液包含（以 mM 表示）：NaCl (5)，CaCl2 (0.1)，MgCl2 (2)，CsCl (10)，CsF (120)，HEPES (10)，EGTA (10)在 pH 7.2 下。 為估計化合物對通道之靜止與失活狀態之穩定狀態親和 力（個別為Kr與Ki)，故對來自保持電位-110 mV之去極化電 壓-60至+90 mV，使用12_5毫秒試驗脈衝，以建立電流-電 壓關係（I-V曲線）。接近IV-曲線尖峰之電壓（-30至0 mV)係在 此實驗之整個其餘部份中作為試驗脈衝使用。然後建構穩 128409 -254 - 200836743 定狀悲失活（有效性）曲線，其方式是在對範圍為_11〇至 mV電位之1秒調節脈衝後，度量8·75毫秒試驗脈衝期間所 活化之電流。為監測穩定狀態下之通道，係產生具有保持 電位-110 mV之單一 ”曰記”擬案，以記錄靜止狀態電流⑽ 宅秒試驗脈衝），快速失活後之電流（5毫秒前脈衝為·8〇至 -50 mV，接著為1〇毫秒試驗脈衝），及在各種保持電位期 間之電流（35毫秒激升至試驗脈衝程度）。化合物係在，，日 記’’擬案期間施加，而阻斷係在15秒間隔下監測。 在化合物達成平衡後，於化合物存在下，測定穩定狀態 失活之電壓依存性。會阻斷通道靜止狀態之化合物，會降 低試驗脈衝期間自所有保持電位誘出之電流，然而主要是 阻斷失活狀態之化合物，會降低試驗脈衝期間在較被去極 化電位下所誘出之電流。於靜止狀態下之電流(1靜止)與在失 活狀態期間之電流(1失)係被用以計算化合物之穩定狀態親 和力。以Miehaelis—Menton抑制模式為基礎，&amp;與％係被計算 為個別造成I靜止或！失之50%抑制所需要之化合物濃度。°介 %抑制 =VmaX*[藥物t [藥物]h+Kmh vmax為抑制速率，h為而係數（對交互作用位置），κ為 Michaelis-Menten常數’及[藥物]為待測化合物之濃度。在f靜止 或工失之抑制（1/2ν_)下，藥物濃度係於數字上等於 且個別近似Kr與Kj。 生物學實例3 藉由鈉通道阻斷劑所弓丨致之止痛 128409 -255 - 200836743 熱引致之尾部輕彈潛伏期試驗 在此項試驗中，藉由投予本發明化合物所產生之止痛作 為係在老氣中經過熱引致之尾部輕彈觀察。此項試驗包 ,、、、源#包括投影燈，具有光束，經聚焦且指向被測全式 老二尾部之-個點上。尾部輕彈潛伏期，其係在藥物治療 之::砰估’且回應有害熱刺激’意即從施加輻射熱於尾部 之月側表面上，至發生尾部輕彈之回應時間，係在4〇、8〇、 120及160分鐘下度量與記錄。 對此項研究之第一部份’65隻動物係接受基線尾部輕彈 潛伏期之評估，n，歷經兩個連續天。然後，將此 等動物隨機地指定至n個不同處理組之_，包括媒劑對昭 物：：啡對照組及9種化合物，在3〇毫克/公斤下，以肌内 方式杈予。在劑量投藥之後，密切地監測動物之毒性跡象， 包：震顫或發作、活動過度、淺臥、快逮或抑制之呼吸及 未能=梳。對各化合物之最適宜誘導時間，係經由回歸分 析測定。待測化合物之止痛活性係被表示為最大可能作用 之百分比（％MPE)，並使用下式計算： 截止時間（10秒）-服藥前潛伏期 X 100% 0/〇MPE 伏期-服藥前潛j犬期 其中 服樂後潛伏期=在接受藥物後，尾部移離（輕彈）熱源前， 各個別動物所花費之潛伏時間。 :樂珂潛伏期=在接受藥物之前’於尾部輕彈離開熱源 之如’各個別動物所花費之潛伏時間。 128409 -256- 200836743 截止日T間（10秒）=為對熱源之最高曝露。 急性疼痛（福馬林試驗） 、細馬K驗係作為急性疼痛之動物模式使用。在福馬林 式驗中係、使動物在實驗天前之當天，短$地習慣有機玻 璃试驗室20分鐘。在試驗當天，將動物隨機地注射試驗物 件。於藥物投藥後3〇分鐘時，將5〇微升1〇%福馬林以皮下方 式注射至大白祝左後足掌之足底表面中。影像數據獲取係 在^田馬林技藥後立即開始，歷經分鐘延續時間。 影像係使用Actimetrix Limelight軟體拍攝，其儲存檔案於 *·11η延伸區，然後使其轉化成_£(}_4編碼。然後，使用行 為刀析軟體觀察者5·1”（5·〇版，Noldus資訊技術，Wageningen， The Netherlands)分析影像。影像分析係藉由注意動物行為， 並根據類型將每一項記分，及界定行為長度而達成 (Dubmsson與Dennis，1977)。被評分之行為包括：⑴正常行為， (2)未置放重量於該足掌上，（3)提高該足掌，⑷舐/咬或刮 搔名足莩。經注射足掌之升高、關照或過度紙、咬及刮搔， 係顯示疼痛回應。若兩足掌均靜止於地板上，未具有經注 射足掌之顯著關照，過度舐、咬或刮搔，則顯示來自化合 物之止痛回應或保護。 福馬林試驗數據之分析，係根據兩項因數進行：⑴百分 比隶局可能抑制作用（％MPIE)與（2)疼痛評分。％MPIE係藉由 一系列步驟計算，其中第一個係將每隻動物之非正常行為 (行為1，2,3)之長度加總。媒劑組之單一數值係經由將媒劑處 理組内之所有評分平均而獲得。下列計算係產生每隻動物 128409 -257 - 200836743 之MPIE值： MPIE (/〇) - 100 -[(處理總和/平均媒劑值）χ IQ。％] 疼痛評分係計算自如上述之加權尺度。將行為之延續時 間乘以加權值（回應嚴重性之等級），並除以觀察之總長 度’以測疋母隻動物之疼痛等級。計算係以下式表示： 疼痛等級=[〇(To) + 1(T1) + 2(T2) + 3(T3)]/(To + T1 + T2 + T3) 本發明化合物在30毫克/公斤與〇1毫克/公斤之範圍内， 經証實有效。 * CFA所引致之慢性炎性疼痛 在此項試驗中，觸覺感覺異常係以經校準iv〇nFrey纖絲 評估。在適應飼養所設備一整週後，將15〇微升，，完全Freund 氏佐劑（CFA)乳化液（CFA被懸浮於油/鹽水（丨：丨）乳化液中， 在〇·5耄克/毫升之濃度下），於輕微異弗烷（is〇flurane)麻醉下， 以皮下方式注射至大白鼠左後足掌之足底表面中。使動物 自麻醉恢復，並於CFA投藥後一週，評估所有動物之基線 熱與機械感受傷害低限。於實驗開始前當天，使所有動物 習慣實驗設備20分鐘。將待測與對照物件投予動物，並在 藥物投予後之限定時間點下’度量感受傷害低限，以測定 對/、種可採用治療藥品之每一個之止痛回應。所使用之時 間點係預先決定’以對各試驗化合物顯示最高止痛作用。 動物之熱感受傷害低限值係使用Hargreaves試驗評估。將 動物放置在膠質玻璃封閉物中，經設置在具有加熱單元之 升同玻㈣平台上方。玻璃平台對所有試驗嘗試係經恒溫控 制在大約3G°C之溫度下。在安置至封閉物之後，允許動物 128409 - 258 - 200836743 k應20刀n ’直到停止所有探查行為為止。使用⑽型足底 /尾邛刺激态止痛計（IITC，w〇〇dland腿，ca)，以自玻璃平台 下方施加輻射熱束至後；^掌之^底表面。在所有試驗嘗試 期間，熱源之空轉強度與活性強度係個別設定於丨與必下， 且採用20秒之截止時間，以防止組織傷害。 動物對觸覺刺激之回應低限值，係按試驗， 使用2290型Electrovonfrey麻醉計（IITC生命科學，肠〇(11—匪s， CA)度量。將動物放置在升高之膠質玻璃封閉物中，經設置 在泥濘網片表面上。順應10分鐘後，將預先校準之v〇nFrey 毛髮垂直施加至動物兩足掌之足底表面上，以上升順序， 從0.1克毛髮開始，具有足夠力，以造成毛髮對著足掌之稍 微彎曲。持續測試，直到測定出具有最低力之毛髮引致足 掌之快速輕彈，或當達到截止力為大約20克為止。使用此 截止力’因其表示大約10〇/。之動物體重，且其係用以防止 由於利用較僵硬毛髮所致之整個肢體升高，這將改變刺激 之性質。本發明化合物經証實在3〇毫克/公斤與〇1毫克/公 斤之範圍内為有效的。 感受傷害之手術後模式 在此模式中’係度ϊ因在足掌中之足底内切開術所造成 之痛覺過敏，其方式是對足掌施加增加之觸覺刺激，直到 動物自所施加之刺激縮回其足掌。當動物在3·5%異氟燒 (Isofluorane)下麻醉（其係經由鼻錐傳輸）時，使用1〇號解剖刀 片，在左後足掌之足底方面中，造成1公分縱向切口，經過 皮膚與筋膜，距腳跟之近基邊緣0.5公分開始，並延伸朝向 128409 -259- 200836743 腳趾。於切開後，使用2,3-0殺菌絲縫合線，使皮膚放在附 近將已文傷害之位置以多史潑菌素與貝達汀（betadine)覆 蓋。使動物返回其原本籠子，供過夜恢復。 ^ ;、、二手術（同側）與未經手術（對側）兩足掌，動物對觸 覺刺激之縮回低限值，可使用2290型Electr〇v〇nfrey麻醉計 (IITC生命科學，woodland Hills，CA)度量。將動物放置在升高 之膠質玻璃封閉物中，經設置在泥濘網片表面上。於適應 至少10分鐘後，將預先校準之vonFrey毛髮垂直施加至動物 兩足掌之足底表面，以上升順序，自10克毛髮開始，具有 足夠力，以造成毛髮對著足掌稍微彎曲。持續測試，直到 測定出毛髮以最低力引致足掌之快速輕彈，或當達到大約 20克之截止力為止。使用此截止力，因其表示大約1〇%之 動物體重，且其係用以防止由於利用較僵硬毛髮所致之整 個肢體升而’這將改變刺激之性質。 本發明化合物經註實在30毫克/公斤與〇1毫克/公斤之範 圍内為有效的。 神經病原性疼痛模式；慢性挾縮損傷 簡言之，係在動物左後腳之中大腿層次處，使用1〇號解 剖刀片，經過皮膚與筋膜，造成大約3公分切口。經由鈍器 解剖經過股二頭肌，使左邊坐骨神經外露，小心使出血降 至最低。將四個鬆散缚線沿著坐骨神經，使用4_〇不可降解 經殺菌絲縫合線，每隔1至2毫米間隔打結。當在解剖顯微 鏡下，於4倍放大倍率下觀察時，鬆散缚線之張力係足夠緊 密’以引致坐骨神經之輕微挾縮。在模擬操作動物中，係 128409 -260- 200836743 使左邊坐骨神經外露，而未進一步處理。將抗細菌軟膏直 接塗敷至傷口中，並使用經殺菌縫合線，使肌肉閉合。將 貝達汀（betadine)塗敷至肌肉及其周圍上，接著以手術夾使皮 膚閉合。 動物對觸覺刺激之回應低限值，係使用229〇型 Electrovonfrey麻醉計（IITC生命科學，w〇〇dland扭❿，cA)度量。 將動物放置在升南之膠質玻璃封閉物中，經設置在泥濘網 片表面上。於順應10分鐘後，將預先校準之v〇nFrey毛髮垂 直施加至動物兩足掌之足底表面，以上升順序，自0 1克毛 髮開始，具有足夠力，以造成毛髮對著足掌之稍微彎曲。 持續測試，直到測定出毛髮以最低力引致足掌之快速輕 彈’或當達到大約20克之截止力為止。使用此截止力，因 其表示大約10%之動物體重’且其係用以防止由於利用較 僵硬毛髮所致之整個肢體升高，這將改變刺激之性質。本 發明化合物經註實在3 0毫克/公斤與〇 ·丨毫克/公斤之範圍内 為有效的。 動物之熱感受傷害低限值係使用Hargreaves試驗評估。在 觸覺低限值度量之後’將動物放置在膠質玻璃封閉物中， 經設置在具有加熱單元之升高玻璃平台上方。玻璃平台對 所有試驗嘗試係經恒溫控制在大約24至2fC之溫度下。在 安置至封閉物之後，允許動物適應10分鐘，直到停止所有 探查行為為止。使用226型足底/尾部刺激器止痛計（IITc, Woodland Hills，CA)，以自玻璃平台下方施加輻射熱束至後足 掌之足底表面。在所有試驗嘗試期間，熱源之空轉強度與 128409 -261 - 200836743 活性強度係個別設，且使㈣秒之截止時間 以防止組織傷害。 生物學實例4 烏頭素所引致之節律不齊試驗 本發明化合物之抗節律不齊活性係藉由下述試驗証實。 節律不齊係藉由靜脈内投予已溶於生理食鹽水中之烏頭素 (2·〇微克/公斤）而被誘發。待測化合物係在烏頭素投藥後， 以靜脈内方式投予5分鐘。抗節律不齊活性之評估係藉由度 量從烏頭素投藥至發生期外收縮（ES)之時間，與從烏頭素 投藥至發生心室搏動過速（VT)之時間進行。 在異弗烷（iS〇fhirane)(2%之1/4至1/3)麻醉下之大白鼠中，進 仃氣管切開術，藉由首先在頸部區域中建立切口，然後單 離氣笞，並造成2宅米切口，以插入氣管管件進入氣管中2 公分，以致管件之開口正好位於口部上方。將管件以縫合 線固定，並連接至通風器，歷經實驗期間。 」後，於股區域中造成切口（2·5公分），並使用鈍器解剖 如針’單離股血管。將兩個股靜脈插管，一個供戊巴比妥 ^醉劑維持（0.02-0.05毫升），而一個供灌注與注射藥物及媒 劑。將股動脈以傳送器之血壓凝膠導管插管。 使ECG導線連接至胸肌，在導線π位置（右上方/心臟上方 -白色導線，與左下方/心臟下方-紅色導線）。導線係以縫 合線固定。 將所有手術區域使用以0.9%鹽水濕潤之紗布覆蓋。供應 （Μ·5毫升，〇·9%溶液）以濕潤手術後區域。使動物之 128409 -262- 200836743 ECG與通氣平衡至少3〇分鐘。 節律不齊係以2微克/公斤/分鐘烏頭素灌注5分鐘而被引 致。在此段期間内，記錄ECG並連續地監測。待測化合物 之靜脈内大丸劑注射（10、30或100微克/公斤），會造成完全 返回正常基線ECG。 因此，本發明化合物，當在此模式中測試時，係展現抗. 節律不齊活性。 生物學實例5 絕血引致之節律不齊試驗 心室節律不齊之齧齒動物模式，在急n轉向術與預 防範例兩者中，已被採用於測試潛在治療劑，供人類中之 心房與心室節律不齊兩者用。會導致心肌梗塞之心臟絕血， 係為發病率與死亡率之常見原因。化合物預防絕血所引致 之心室搏動過速與纖維顫動之能力，係為所接受之模式， 用於敎化合物在臨床環境中對於心、房與心、室搏動過速與 纖維顏動之功效。 將在第4與第5根肋骨間之胸部打開， 口，以致心臟可見及。將各大白鼠放置在 將金屬約束器鈎住肋骨骨架，打開胸腔。 麻醉係首先藉由戊巴比妥（腹膜腔内）引致，並藉由靜脈 ，大丸劑灌注保持著。雄性SDA白鼠具有其以套管插入之 氣管’以室内空氣進行人工通氣，在每搏量lG毫升/公斤下， 6〇搏/分鐘m邊股缝與㈣“χρΕ5()管件插管，個別供 平均動脈域(MAP)記錄，與化合物之靜脈内投藥。 以產生1.5公分開 凹口平台上，並 使用縫合針以穿 128409 -263 - 200836743 並在向下對角線方向上離 透心室’正好在升高前房下方 出口位置 。將縫合 形成。然 〇 供ECG度 開心室，以致將獲得&gt;30%至&lt;50%閉塞區帶（〇z)。 係低於其中主動脈連接至左心室處下方〜〇.5公分 線拉緊，以致鬆散線圈（閉塞物）係環繞動脈支管 後，使胸部以可進入胸部外部之閉塞物末端閉合 將電極置於導線II位置（右邊前房至頂端）中， 量，如下述：將一個電極插入右前掌中， ^ l Λ 羊甲，而另一個電極插 入左後足掌中。 體溫、MAP、ECG及心跳速率係不斷地在整個實驗中記 錄。一旦關鍵參數已被安定化，即取得丨_2分鐘記錄，以建 立基線值。-旦基線值被建立，即起始該化合物或對照物 質之灌注。於化合物或對照物之5_分鐘灌注後，將縫合線 拉緊以結紮LCA，並在左心室中造成絕血。於結紮後，連 續記錄關鍵參數20分鐘，除非MAP達到臨界程度2〇_3〇毫米 Hg，歷經至少3分鐘，於此種情況中，即停止記錄，因為動 物將被宣告死亡，然後使其犧牲。此化合物預防節律不齊 且維持接近正常MAP與HR之能力，係經評分並與對照組比 較0 本發明化合物，當在此模式中測試時，係展現預防絕血 所引致心室搏動過速與纖維顫動之能力。 生物學實例6 關於良性攝護腺增生（BPH)之活體内檢測 本發明化合物用於治療BPH之有效性係藉由下述活體内 檢測f正實。 128409 -264- 200836743 使狗在〇写克/公斤與100毫克/公斤間之口服劑量下，經 服用本t明化合物，歷經4週期間。對照組係接受安慰劑。 使動物犧牲’ ϋ將攝護腺解剖出來，輕拍使其乾燥，然後 2重田與經媒劑處理（〇毫克/公斤）之對照組比較時，証 :本發明化合物在顯著地降低狗之攝護腺重量上，係以劑 里依賴方式，於5毫克/公斤與1〇〇毫克/公斤之範圍内為有 效，此等化合物沒有任何不利事件，使得彼等成為安全治 療ΒΡΗ與有關聯病徵（譬如但不限於急性尿滞留與尿道感 染）之理想候選者。 生物學實例7 關於抗高膽固醇血症功效與抗動脈粥瘤硬化劑功效之活體 内檢測 本t月化合物係具有抗高膽固醇血症功效與抗動脈粥瘤 硬化劑功效，如藉由其在下述檢測中之活性所証實者。 狗具有類似人類之心血管系統，使得彼等理想地用於研 九經设計以治療心血管病症之醫藥化合物之作用。 使狗在0毫克/公斤至1〇〇毫克/公斤之範圍下，每日經口 服用本發明化合物，歷經2-4週期間。在2與4週後，將動物 採血，並收集其血清，供總膽固醇分析，且與服用單獨媒 劑（〇毫克/公斤）之動物作比較。 ” 膽固醇之度量係4臨床實驗室環土竟中所進行冑常見試驗 之一。經常使用關於血漿或血清中總膽固醇之敏感性定量 之簡單螢光汁方法。於一種檢測中，係首先使試樣中之膽 固醇基i曰類藉由膽固醇酯酶水解。然後，使所有贍固醇， 128409 -265 - 200836743 無論是預先經醋化或在循環中 卜 盾衣中之現有自由態，藉由膽固醇 氧化酶氧化成其相應之鲷與過氧化氯。adhp(i〇_乙酿基私 二經基啡十井）係作為過氧化氫之高度地敏感性與安定探 測物使用。辣根過氧化酶會催&lt;tADHP與過氧化氫之反應， 產生高度地螢光產物瑞奢‘a/ 祐宗如为（resorufin)，其可使用565-580 毫微米之激發波長與游595毫微米之發射波長監控。 當在上述檢測中，以5-100毫克/公斤之每日口服劑量範圍 投予狗’歷經2-與4-週期間時，树明化合物係顯示影響總 血清膽固醇上之顯著降低之能力。 生物學實例8 關於治療搔癢病之活體内檢測 本發明化合物可藉由活體内試驗，使用齧齒動物模式， 評估關於其作為止疼劑之活性。關於以末梢方式誘發搔爆 病之一種經建立模式，係經過血清素之注射至無毛大白鼠 之嘴側背後區域（頸部）中。在血清素注射（例如2毫克/毫 升50微升）之月ij ’本發明化合物之劑量可經過口腔、靜脈 :或腹膜腔内途徑系統地或以局部方式施用至圓形區域固 定直徑(例如18毫米）。在服藥之後，於局部服藥之區域中 給予血清素注射。於血清素注射後，動物行為係藉由顯像 記錄監控20分鐘-L5小時，並將此段時間中抓疼之次數與 經媒劑處理之動物作比較。因此’本發明化合物之施用可 在大白鼠中壓抑血清素所引致之抓癢。 .，•’ V 个个 於本專利說明書中引用之所有美國專利、美國專利申請 128409 -266 - 200836743 案公報、美國專利申請案、國外專利、國外專利申請案及 非專利刊物，均以其全文併於本文供參考。 雖然前述發明已大致詳細地加以描述以幫助瞭解，但應 明瞭的是，某些改變與修正可在隨文所附請求項之範圍内 ^施H所述具體實施例係被認為是說明性 性，且本發明计b心 F丨良制Example No. Compound name IC5〇 Active content 131 N-[4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]-N-(methylsulfonyl)methanesulfonate Amine D Biological Example 2 Electrophysiological assay (in vitro assay) DMEM growth medium with cells expressing the channel of interest in DMO with 0.5 mg/ml G418, +/-1% PSG and 10% heat-inactivated bovine fetal serum (Gibco), cultured at 37 ° C with 5% CO 2 . For electrophysiological recording, cells were plated on 10 mm culture dishes. Whole-cell recordings were performed using the established whole-cell voltage clamping method (Bean et al., in Cold &quot; 遂之|作尹) using the Axopatch 200B amplifier and Clampex software (Axon Instruments, Union City, CA). All experiments were performed at ambient temperature. The electrode is fired to a 2-4 Mohm resistor, and the voltage error and capacitance artifacts are minimized by series resistance compensation and capacitance compensation. The data was acquired at 40 kHz and filtered at 5 kHz. The external (bath) solution contained: NaCl (140 mM), KC1 (5 mM), CaCl2 (2 mM), MgCl2 (1 mM), and HEPES (10 mM) at pH 7.4. The internal (pipette) solution contains (expressed in mM): NaCl (5), CaCl2 (0.1), MgCl2 (2), CsCl (10), CsF (120), HEPES (10), EGTA (10) at pH Under 7.2. To estimate the steady state affinity of the compound for the stationary and inactive states of the channel (individually Kr and Ki), a demodulation voltage of -60 to +90 mV from the holding potential of -110 mV is used, using a 12-5 ms test pulse to Establish a current-voltage relationship (IV curve). The voltage close to the IV-curve peak (-30 to 0 mV) was used as the test pulse throughout the remainder of the experiment. Then construct a stable 128409 -254 - 200836743 steady-state inactivation (effectiveness) curve by measuring the pulse during the test pulse of 8.75 milliseconds after adjusting the pulse for a period of _11〇 to mV. Current. In order to monitor the channel under steady state, a single "drill" simulation with a holding potential of -110 mV is generated to record the current at rest (10) test pulse), and the current after rapid deactivation (5 milliseconds before the pulse is 8 〇 to -50 mV, followed by a 1 〇 test pulse), and current during various holding potentials (35 milliseconds rise to the test pulse level). Compounds were applied during the diary's case and the blocking lines were monitored at 15 second intervals. After the compound was equilibrated, the voltage dependence of the steady state deactivation was measured in the presence of the compound. Compounds that block the quiescent state of the channel will reduce the current drawn from all holding potentials during the test pulse, but primarily block the inactive state compound, which will reduce the induced voltage during the test pulse. The current. The current in the quiescent state (1 quiescent) and the current during the deactivation state (1 lapse) are used to calculate the steady state affinity of the compound. Based on the Miehaelis-Menton suppression mode, & and % are calculated as individual I or still! The concentration of the compound required to inhibit 50% of the loss. °% inhibition = VmaX* [drug t [drug] h+Kmh vmax is the inhibition rate, h is the coefficient (for the interaction position), κ is the Michaelis-Menten constant' and [drug] is the concentration of the test compound. At f standstill or inhibition of work loss (1/2 ν _ ), the drug concentration is numerically equal and individual approximations Kr and Kj. Biological Example 3 Analgesic pain caused by a sodium channel blocker 128409 - 255 - 200836743 Thermally induced tail flick latency test In this test, the pain caused by administration of the compound of the present invention is used as a lineage. In the old gas, the tail is flicked by heat. The test package, , , and source # include a projection lamp with a light beam that is focused and pointed at a point of the measured omnipresent tail. The tail flicking latency, which is in the medical treatment:: 砰 ' 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加 施加Measurements and records under 〇, 120 and 160 minutes. For the first part of the study, '65 animals received an assessment of the baseline tail flick latency, n, for two consecutive days. Then, these animals were randomly assigned to n different treatment groups, including vehicle-to-preparation: a control group of thyroid and 9 compounds, which were administered intramuscularly at 3 mg/kg. After dose administration, the animal's signs of toxicity are closely monitored, including: tremor or seizures, hyperactivity, shallow lying, fast catching or inhibiting breathing and failure = combing. The optimum induction time for each compound was determined by regression analysis. The analgesic activity of the test compound is expressed as a percentage of the maximum possible effect (%MPE) and is calculated using the following formula: Cut-off time (10 seconds) - pre-dose latency X 100% 0 / 〇 MPE volt - predatory j Latency in the dog period after the service = the latency of each individual animal before the tail is removed (lightly bombed) after receiving the drug. : Le 珂 latency = the latency of the individual animals that flew away from the heat source at the end of the drug before receiving the drug. 128409 -256- 200836743 Deadline T (10 seconds) = the highest exposure to heat source. Acute pain (formalin test) and fine horse K test are used as animal models of acute pain. In the Formalin test, the animals were accustomed to the organic glass laboratory for 20 minutes on the day before the test day. On the day of the experiment, the animals were randomly injected into the test article. At 3 minutes after the drug was administered, 5 liters of microliters of 1% of formalin was injected subcutaneously into the plantar surface of the left hind paw of Dabaizhu. The image data acquisition system begins immediately after the ^Mallin technique, and lasts for a minute. The image was taken using the Actimetrix Limelight software, which stores the file in the *·11η extension and then converts it into _£(}_4 encoding. Then, using the behavioral knife to analyze the software observer 5.1" (5·〇版, Noldus Information Technology, Wageningen, The Netherlands) Analyze images. Image analysis is achieved by paying attention to animal behavior and assigning each score according to type and defining the length of the behavior (Dubmsson and Dennis, 1977). (1) normal behavior, (2) no weight placed on the palm of the foot, (3) raising the sole of the foot, (4) licking/biting or scraping the name of the foot. After the injection of the foot, the care or over-paper, bite Scraping, showing pain response. If both feet are resting on the floor, without significant care of the injected foot, excessive sputum, bite or scraping, it shows analgesic response or protection from the compound. The analysis was based on two factors: (1) percent inhibition of possible inhibition (%MPIE) and (2) pain score. %MPIE was calculated by a series of steps, the first of which was abnormal for each animal The sum of the lengths of (acts 1, 2, 3) is obtained by averaging all the scores in the vehicle treatment group. The following calculations yield MPIE values of 128409 - 257 - 200836743 per animal. : MPIE (/〇) - 100 - [(Processing Sum/Average Media Value) χ IQ.%] The pain score is calculated from the weighted scale described above. Multiply the duration of the behavior by the weighted value (level of response severity) And divide by the total length of observation to measure the pain level of the female animal. The calculation is expressed as follows: Pain level = [〇(To) + 1(T1) + 2(T2) + 3(T3)]/ (To + T1 + T2 + T3) The compound of the present invention was confirmed to be effective in the range of 30 mg/kg and 〇1 mg/kg. * Chronic inflammatory pain caused by CFA In this test, tactile sensory abnormality Evaluated with calibrated iv〇nFrey filaments. After a full week of adaptation to the feeding facility, 15 liters of microliters, complete Freund's adjuvant (CFA) emulsion (CFA was suspended in oil/saline (丨:丨) In the emulsion, at a concentration of 耄·5耄g/ml, under anesthesia with a slight flurane The rats were injected subcutaneously into the plantar surface of the left hind paw of the rats. The animals were recovered from anesthesia and the baseline thermal and mechanical nociceptive lows of all animals were evaluated one week after CFA administration. All animals were accustomed to the experimental equipment for 20 minutes. The animals to be tested and the control were administered to the animals, and the lower limit of the nociceptive was measured at a defined time point after the administration of the drug to determine the pain relief of each of the therapeutic drugs. Respond. The time points used were predetermined to show the highest analgesic effect on each test compound. The lower limit of thermal sensation in animals was assessed using the Hargreaves test. The animals were placed in a colloidal glass enclosure and placed over a platform with a heating unit. The glass platform was thermostatically controlled at a temperature of approximately 3 G ° C for all test attempts. After placement to the enclosure, animals 128409 - 258 - 200836743 k are allowed to be 20 kn' until all exploration is stopped. Use the (10) type of foot/tail stimuli analgesic meter (IITC, w〇〇dland leg, ca) to apply a radiant heat beam from below the glass platform to the back; During all trial attempts, the idling intensity and activity intensity of the heat source were individually set at 丨 and must be with a 20 second cut-off time to prevent tissue damage. The animal's low response to tactile stimuli was measured by a model 2290 Electrovonfrey anesthesia (IITC Life Sciences, Intestinal Hemorrhoids (11-匪s, CA). The animals were placed in an elevated colloidal glass enclosure, Placed on the surface of the loach mesh. After 10 minutes, the pre-calibrated v〇nFrey hair is applied perpendicularly to the sole surface of the animal's two feet, starting from 0.1 g of hair in ascending order, with sufficient force to Causes the hair to bend slightly against the sole of the foot. Continue testing until the hair with the lowest force is detected to cause a rapid flick of the foot, or when the cut-off force is about 20 grams. Use this cut-off force 'because it represents about 10 The weight of the animal is used to prevent the entire limb from rising due to the use of stiffer hair, which will alter the nature of the stimulus. The compounds of the invention have been shown to be at 3 mg/kg and 1 mg/kg. Within the scope of the effect. The post-operative mode of receptive injury in this mode is the hyperalgesia caused by the incision in the sole of the foot. Increase the tactile stimulus until the animal retracts its foot from the applied stimulus. When the animal is anesthetized with 3.5% isoflurane (which is transmitted via the nose cone), use a 1 解剖 anatomical blade, In the sole of the left hind paw, a longitudinal incision of 1 cm is made through the skin and fascia, starting at 0.5 cm from the proximal edge of the heel and extending towards the toe of 128409 -259-200836743. After cutting, use 2, 3-0 sterilizing silk suture, so that the skin is placed nearby to cover the position of the wounded with multiple sputum and betadine. The animal is returned to its original cage for overnight recovery. ^ ;, 2 Surgery (ipsilateral) and non-surgical (contralateral) both feet, the animal's retraction threshold for tactile stimulation can be measured using the Model 2290 Electronv〇nfrey anesthesia (IITC Life Sciences, Woodland Hills, CA) The animals are placed in an elevated colloidal glass enclosure and placed over the surface of the loach. After at least 10 minutes of adaptation, the pre-calibrated von Frey hair is applied perpendicularly to the sole surface of the animal's feet to rise. Order, from 10 grams Start with enough force to cause the hair to bend slightly against the sole of the foot. Continue testing until the hair is measured to cause a rapid flick of the foot with minimal force, or when a cut-off force of approximately 20 grams is reached. Using this cut-off force, Since it represents about 1% of the animal's body weight, and it is used to prevent the entire limb from rising due to the use of stiffer hair, 'this will change the nature of the stimulus. The compound of the invention is labeled at 30 mg/kg with 〇1 Effective in the range of mg/kg. Neuropathogenic pain pattern; chronic contracture damage, in short, at the thigh level in the left hind foot of the animal, using a 1 解剖 anatomical blade, through the skin and fascia, causing approximately 3 cm incision. The biceps nerve is exposed through a blunt dissection through the biceps femoris, and care is taken to minimize bleeding. Four loose lines were placed along the sciatic nerve, using 4_〇 non-degradable sterilized silk sutures, knotted at intervals of 1 to 2 mm. When viewed under anatomical microscopy at 4x magnification, the tension of the loose binding line is sufficiently tight to cause a slight contraction of the sciatic nerve. In mock-operated animals, lines 128409-260-200836743 exposed the left sciatic nerve without further processing. The antibacterial ointment is applied directly to the wound and the sterilized suture is used to close the muscle. Betadine is applied to the muscle and its surroundings, and the skin is closed with a surgical clip. Animals responded to low limits on tactile stimuli using the 229〇 Electrovonfrey anesthesia meter (IITC Life Sciences, w〇〇dland torsion, cA). The animals were placed in a gelatin glass enclosure of Shengnan and placed on the surface of the loach web. After 10 minutes of compliance, the pre-calibrated v〇nFrey hair was applied perpendicularly to the sole surface of the animal's two feet, starting in the ascending order, starting from 0 1 gram of hair, with sufficient force to cause the hair to face slightly to the sole of the foot. bending. The test is continued until the hair is measured to cause a rapid flick of the paw with minimal force or when a cut-off force of approximately 20 grams is reached. This cut-off force is used because it represents about 10% of the animal's weight&apos; and it is used to prevent the entire limb elevation due to the use of stiffer hair, which will alter the nature of the stimulus. The compound of the present invention is effective in the range of 30 mg/kg and 〇·丨 mg/kg. The lower limit of thermal sensation in animals was assessed using the Hargreaves test. The animal is placed in the colloidal glass enclosure after the tactile low limit metric, disposed over the elevated glass platform with the heating unit. The glass platform was thermostatically controlled at a temperature of approximately 24 to 2 fC for all test attempts. After placement in the enclosure, the animals are allowed to acclimate for 10 minutes until all exploration is stopped. A Model 226 Foot/Tail Stimulator Analgesic (IITc, Woodland Hills, CA) was used to apply a radiant heat beam from beneath the glass platform to the plantar surface of the hind paw. During all trial attempts, the idling intensity of the heat source was individually set to 128409 - 261 - 200836743 and the cut-off time was (four) seconds to prevent tissue damage. Biological Example 4 Arrhythmia Test Affected by Aconitine The anti-arrhythmia activity of the compound of the present invention was confirmed by the following experiment. Rhythm is induced by intravenous administration of aconitin (2·〇 microgram/kg) dissolved in physiological saline. The test compound was administered intravenously for 5 minutes after administration of aconitine. The assessment of anti-arrhythmia activity was performed by the time from the administration of aconitine to the onset of external contraction (ES), and from the time of administration of aconitine to the onset of ventricular tachycardia (VT). In a rat under anesthesia with iS〇fhirane (1% to 1/3 of 2%), a tracheotomy was performed, by first creating an incision in the neck region and then leaving the gas. And caused a 2 house meter cut to insert the tracheal tube into the trachea 2 cm, so that the opening of the tube is just above the mouth. The tube was secured with a suture and attached to a ventilator during the experiment. After that, an incision (2.5 cm) was made in the femoral region, and a blunt dissection was used, such as a needle, to separate the femoral blood vessels. Two femoral veins were cannulated, one for pentobarbital (about 0.02-0.05 ml), and one for perfusion and injection of drugs and vehicles. The femoral artery was cannulated with a blood pressure gel catheter of the transmitter. Connect the ECG lead to the pectoral muscle at the π position of the lead (upper right / above the heart - white lead, with the lower left / below the heart - red lead). The wire is fixed with a seam. All surgical areas were covered with gauze moistened with 0.9% saline. Supply (Μ·5 ml, 〇·9% solution) to moisten the area after surgery. Animals were allowed to equilibrate with 128409-262-200836743 ECG for at least 3 minutes. The rhythm was induced by infusion of 2 μg/kg/min of aconite for 5 minutes. During this period, the ECG is recorded and continuously monitored. Intravenous bolus injection (10, 30 or 100 μg/kg) of the test compound will result in a complete return to normal baseline ECG. Thus, the compounds of the invention, when tested in this mode, exhibit anti-rrhythmia activity. Biological example 5 Arrhythmia caused by arrhythmia The rodent pattern of ventricular arrhythmia has been used to test potential therapeutic agents for atrial and ventricular rhythms in humans in both acute n-stealing and prevention paradigms. Not both. Cardiac arrhythmia, which causes myocardial infarction, is a common cause of morbidity and mortality. The ability of compounds to prevent ventricular tachycardia and fibrillation caused by blood loss is a accepted mode for the efficacy of bismuth compounds in heart, room and heart, ventricular tachycardia and fiber sensation in a clinical setting. The chest between the 4th and 5th ribs will open, so that the heart is visible. Place the rats in the metal frame to hook the rib cage and open the chest. The anesthesia was first induced by pentobarbital (intraperitoneal) and maintained by intravenous, bolus infusion. Male SDA rats have their trachea inserted into the cannula's artificial ventilation with indoor air, at a stroke volume of 1G ml/kg, 6 strokes/min m-side sewn and (4) “χρΕ5() tube intubation, individual supply Mean Arterial Domain (MAP) was recorded, administered intravenously with the compound. To create a 1.5 mm separate notch platform, and use a suture needle to wear 128409-263 - 200836743 and in the downward diagonal direction away from the ventricle' In the lower exit position of the anterior chamber, the suture will be formed. Then the ECG will be happy, so that it will get &gt;30% to &lt;50% occlusion zone (〇z). The system is lower than the aorta connected to the left. The lower part of the ventricle is lower than the 〇.5 cm line, so that the loose coil (occlusion) surrounds the artery branch, so that the chest is closed at the end of the occlusion that can enter the chest, and the electrode is placed in the position of the wire II (right anterior chamber to the top) Medium, quantity, as follows: Insert one electrode into the right forefoot, ^ l 羊 羊甲, and the other electrode into the left hind paw. Body temperature, MAP, ECG, and heart rate are continuously recorded throughout the experiment. Reference The number has been stabilized, ie a 丨_2 minute record is taken to establish a baseline value. Once the baseline value is established, the perfusion of the compound or control substance is initiated. After the 5 minute infusion of the compound or control, The suture is tightened to ligate the LCA and cause septicemia in the left ventricle. After ligation, the key parameters are continuously recorded for 20 minutes unless the MAP reaches a criticality of 2〇_3〇mm Hg for at least 3 minutes. In the middle, the recording is stopped because the animal will be declared dead and then sacrificed. This compound prevents the rhythm and maintains the ability to approach normal MAP and HR, is scored and compared with the control group 0 compound of the invention, when When tested in the model, it demonstrates the ability to prevent ventricular tachycardia and fibrillation caused by hematopoiesis. Biological Example 6 In vivo detection of benign prostatic hyperplasia (BPH) The effectiveness of the compounds of the invention in the treatment of BPH The positive in vivo test was carried out by the following in vivo. 128409 -264- 200836743 The dog was administered with the compound of t in the oral dose of gram/kg and 100 mg/kg for 4 weeks. The control group received a placebo. The animal was sacrificed 'ϋ The prostate was dissected out, patted to dry, and then the 2 field was compared with the control group treated with vehicle (〇mg/kg). The compounds of the invention are effective in reducing the weight of the dog's prostate in a dose-dependent manner, in the range of 5 mg/kg and 1 mg/kg, and these compounds do not have any adverse events, making them It is an ideal candidate for safe treatment of sputum and associated symptoms such as, but not limited to, acute urinary retention and urinary tract infections. Biological Example 7 In vivo detection of anti-hypercholesterolemia efficacy and anti-atheroma sclerosing agent efficacy The monthly compound has anti-hypercholesterolemia efficacy and anti-atheroma sclerosing agent efficacy, as evidenced by its activity in the assay described below. Dogs have a human-like cardiovascular system that makes them ideally suited for the study of the role of pharmaceutical compounds designed to treat cardiovascular disorders. The compound of the present invention is orally administered to the dog at a dose ranging from 0 mg/kg to 1 mg/kg for 2-4 weeks. After 2 and 4 weeks, the animals were bled and their serum was collected for total cholesterol analysis and compared to animals taking a separate vehicle (〇 mg/kg). The measurement of cholesterol is one of the common tests performed in the clinical laboratory. It is often used as a simple fluorescent juice method for quantifying the sensitivity of total cholesterol in plasma or serum. In one test, the first test is performed. The cholesterol-based steroids in the sample are hydrolyzed by cholesterol esterase. Then, all steroids, 128409-265 - 200836743, either pre-acetified or in the circulation of the existing free state in the shield, by cholesterol The oxidase is oxidized to its corresponding hydrazine and chlorine peroxide. Adhp (i〇) is used as a highly sensitive and stable probe for hydrogen peroxide. Horseradish peroxidase It will prompt the reaction of &lt;tADHP with hydrogen peroxide to produce a highly fluorescent product, resauer'a/resorufin, which can use an excitation wavelength of 565-580 nm and an emission wavelength of 595 nm. Monitoring. When the dog was administered to the dog at a daily oral dose ranging from 5 to 100 mg/kg in the above test, the compound showed a significant effect on the total serum cholesterol. Biological Example 8 In vivo detection of the treatment of scrapie The compound of the present invention can be evaluated for its activity as an analgesic by an in vivo test using a rodent model. Regarding an established mode of inducing a blast disease in a peripheral manner, Serotonin is injected into the back area (neck) of the mouth of the hairless rats. The dose of the compound of the present invention can be passed through the oral cavity and vein during the serotonin injection (for example, 2 mg/ml 50 μl). Or the intraperitoneal route is administered systemically or locally to a circular area of fixed diameter (eg 18 mm). After administration, serotonin is administered in the area of topical administration. After serotonin injection, animal behavior is borrowed. The imaging record was monitored for 20 minutes-L5 hours, and the number of pains in this period of time was compared with that of the vehicle treated animals. Therefore, the application of the compound of the present invention can suppress the serotonin caused by the rats. Itching. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Requests, foreign patents, foreign patent applications, and non-patent publications are hereby incorporated by reference in their entireties. The specific embodiments are described as being illustrative in the scope of the claims appended hereto, and the invention is considered to be illustrative.

.^ ” 文限於本文中所予之詳細說日月，A H 在隨文所附4主七^ 凡月，而是可 付响求項之範圍與等效事物内修正。 128409 267-. . . ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ” ”

Claims (1)

200836743 十、申請專利範圍： 1· 一種式（I)化合物： 〇200836743 X. Patent application scope: 1. A compound of formula (I): 〇 其中： η為1至4 ; Q 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、_基、鹵烷 基、i烯基、齒炔基、環烷基、環烷基烷基、環烷基 稀基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基 '雜芳基烯基、雜芳基炔基、_R6_CN、 &quot;R6-N〇2 &gt; . .R6.N(R4)R5 λ .R6.S(〇)pR4 , .R6 .C(〇)R4 , -R6 -C(S)R4、-R6 -C(r4 )2 C(〇)r5、-R6 _C(〇)〇R4、_r6 -〇c(〇)R4、 -R6 -C(S)OR4 、-R6 -C(0)N(R4 )R5 、-R6 -C(S)N(R4 )R5 、 &quot;R6-N(R5 )C(0)R4 ^ -R6-N(R5 )C(S)R4 ^ -R6-N(R5 )C(0)0R4 ^ -R6-N(R5)C(S)OR4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)C(S)-N(R4 )R5、_R6 -N(R5 )S(0)t R4、_R6 -N(R5 )S(0)tN(R4 )R5、 -R6 -S(0)tN(R4 )R5、-R6 -N(R5 )C〇=NR5 )N(R4 )R5 及 _R6 -N(R5)_ C(N=C(R4)R5)N(R4)R5，其中各p係獨立為0, i或2，且各t 係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子— 128409 200836743 起’可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、_烷基、_烯基、_炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R為氫、烧基、浠基、炔基、鹵烧基、鹵烯基、函炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、-R7-N(R4)R5或 -R7-n(r4)c(o)or4 ; 其中環烧基、環烧基烧基、環烧基烯基 '環烧基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 鹵基、鹵烷基、鹵烯基、_炔基、視情況經取代之 環烷基、視情況經取代之環烷基烷基、視情況經取 代之環烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烷基、 128409 200836743 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烧基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、-R6-CN、-R6-N02、-R6-OR5、 &quot;R6-0C(0)R4 . -R6-0S(0)2R4 ^ -R6-C(0)R4 ^ -R6-C(0)0R4 . -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)〇R4 . -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5&gt; S(〇)tR4 . -R6-N[S(0)tR4]2 ^ -R6-N(R5 )C(=NR5 )N(R4 )R5 . -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4].N(R4&gt; C(0)〇R4 . -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 、-R6-N(R5)-R6-OR5 、-r6-s(o)pr4 及 HS(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各t 係獨立為1或2 ; 各R與R5係獨立選自包括氫、烷基、烯基、炔基、齒烷基、 經燒基、烷氧烷基、視情況經取代之環烷基、視情況 ί 經取代之環烷基烷基、視情況經取代之芳基、視情況 、、二取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； ，/、R和彼兩者所連接之氮一起，形成視情況經取代之 雜環基或視情況經取代之队雜芳基； 各汉6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 &quot;、二取代之直鏈或分枝狀次块基鏈；且 128409 200836743 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鍵或分枝狀次炔基鏈； 為其立體異構物、對掌異構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 2·如請求項1之化合物，其中·· η為1至4 ; Q 為稠合芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、齒基、鹵烷 基、i烯基、鹵炔基、環烷基、環烷基烷基、環烷基 稀基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基 '雜芳基烯基、雜芳基炔基、_R6 _CN、 -R6-N〇2、-R6_〇R5、_R6 领R4)R5、-R6-S(〇)pR4、r6 _c(〇)r4、 -R6-C(S)R4 &gt; -R6-C(R4 )2 C(0)R5 - -R6-C(0)〇R4 - -R6-〇C(0)R4 ^ -R6 -C(S)OR4、-R6 -C(0)N(R4 )R5、_R6 -C(S)N(R4 )R5、 -R6-N(R5)C(0)R4、-R6-N(R5)C(S)R4、-R6-N(R5)c(〇)〇R4、 -R6-N(R5)C(S)OR4、-R6-N(R5)C(0)N(R4)R5、-R6_N(R5)C(s)-N(R4)R5、HN(R5)S(〇)tR4、_r6-N(r5)s(〇xn(r4)r5、 •R6 -S(0)tN(R4 )R5 、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 及 -R6-N(R5)C(N=C(R4)R5)N(R4)R5,其中各p 係獨立為 〇, 1 或2， 且各t係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳環原子一起，可 形成稠合環，選自環烷基、芳基、雜環基或雜芳基， 128409 200836743 而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳稀基、^炔基、雜環基、雜環基烧基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烷基、烯基、炔基、鹵烷基、函烯基、_炔基、 罗二燒基、環烧基、環烧基院基、環烧基烯基、環烧基 炔基、芳基、芳烧基、芳烯基、芳炔基、雜環基、雜 %基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、_R7_N(R4)R5或 -R7-n(r4)c(o)or4 ; 其中環烷基、環烷基燒基、環烷基婦基、環烷基快基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代’取代基選自包括烧基、稀基、炔基、 .基、鹵烷基、-烯基、.炔基、視情況經取代之 環烷t、視情況經取代之環烷基烷基、視情況經取 代之％燒基稀基、視情況經取代之環燒基炔基、視 情況經取代之芳基、視情況經取代之芳燒基、視情 况、、、工取代之㈣基、視情況經取代之芳炔基、視情 、取代m環基、視情況經取代之雜環基烧基、 視情況經取代之雜環_基、視情驗取代之雜環 128409 200836743 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、-R6-CN、-R6-N02、-R6-OR5、 -R6-oc(o)R4、-R6-〇s(o)2R4、-R6-C(0)R4、-R6-C(0)0R4、 -R6-c(〇)N(R4)R5、_r6-n(r4)r5、_r6-n(r5)c(0)r4、 -R6-N(R5 )C(0)0R4 ^ -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5&gt; S(0)tR4、-R6_N[S(0)tR4]2、-R6_n(r5)c(=nr5)n(r4)r5 ' -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4].N(R4&gt; C(〇)〇r4 &gt; -R6-N(R5)-R7-N(R4)R5 . -R6-N=C(OR4)R5 . -R6 -N=C(R4 )R5、-R6 -N(R5 )-R6 _0R5、-R6 _S(0)p R4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5㈣兩者所連接之氮―起，形成視情況經取代之 N-雜ί衣基或視情況經取代之队雜芳美· 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烧基 鏈、視情況經取代之直鍵或分枝狀次烯基鏈或視情、i 經取代之直鏈或分枝狀次炔基鏈；且 W為直鏈或分枝狀:欠烧基鏈、直鏈或分枝狀㈣基鍵或直 128409 200836743 鏈或分枝狀次炔基鏈。 3·如請求項2之化合物，其中： η為1至4 ; G、. 為祠合本基， 各R1係獨立選自包括氫、烷基、烯基、炔基、^基、鹵烷 基、i烯基、齒炔基、環烷基、環烷基烷基、環烷基 稀基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 方基、雜方烧基、雜方基稀基、雜芳基快基、_r6_Cn、 -R6-N〇2 - -R6-〇R5 &gt; -R6-N(R4)R5 &gt; -R6-S(0)pR4 &gt; -R6-C(0)R4 &gt; -R6-C(S)R4、-R6-C(R4)2c(0)r5、_r6_c(〇)〇r4、_r6 〇c(〇)r4、 -R6-C(S)OR4、-R6-C(0)N(R4)R5、-R6 -c⑸N(R4 )r5、 -R6-N(R5)C(0)R4、-R6-N(R5)C(S)R4、-R6_N(R5)c(〇)〇R4、 -R6-n(r5)c(s)or4、-r6-n(r5)c(o)n(r4)r5、-R6_n(R5)c(s)_ N(R4 )r5、_R6 -N(R5 )S(0)t R4、-R6 -N(R5 )s(0)t N(R4 )R5、 -R6 -S(0)t N(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 _N(R5 )C(N= 〇讲4瓜5如讲4取5，其中各p係獨立為〇, 1或2，且各^系獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳環原子一起，可 形成稠合環，選自環烷基、芳基、雜環基或雜芳基， 而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烧基、環烧基烧基、環烧基浠基、芳基、芳烧基、 128409 200836743 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烧基、烯基、炔基、_烧基、_烯基、齒炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 快基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烧基、雜環基稀基、雜環基炔基、雜芳基、雜芳 烧基、雜芳基烯基、雜芳基炔基、_R7_N(R4)R5或 -r7-n(r4)c(o)or4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 _基、鹵録、㈣基4快基、視情I經取代之 環烧基、視情況經取代之環烧基燒基、視情況經取 代之環烧基烯基、視情況經取代之^基㈣、視 %代之芳烷基、視情 W况經取代之芳基、視情 況經取代之芳稀基、視情況經取代之芳块基、視情 況經取代之雜環基、視情況經取代之雜環基烧基、 視情況經取狀雜環基縣、視h㈣代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 視情況經取代之雜芳基婦基況經 取代之W基块基、_r6_cn、_r 128409 200836743 -r6-oc(o)r4、-R6-〇S(〇)2R4、-R6-C(0)R4、-R6-C(0)0R4、 -R6-C(0)N(R4)R5、-R6-N(R4)R5、-r6-n(r5)c(o)r4、 -R6-N(R5)C(0)OR4 、 -R6-N(R5 )C(0)N(R4)R5 、 -R6-N(R5)S(0)tR4 、 -R6 -N[S(0)t R4 ]2 、 -R6-N(R5)C(=NR5)N(R4)R5、-r6-N(R5)C(=NR5)N(R4)CN、 -R6 -N(R5 )C[=NC(Q)OR4 ]-N(R4 )-C(0)OR4 、 -R6-N(R5&gt;R7-N(R4)R5 ^ -R6-N=C(OR4)R5 - -R6-N=C(R4)R5 &gt; -R6 -N(R5 )-R6 -〇R5、-R6 -S(〇)p R4 及-R6 n(r4 )r5，其中 各p係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R:和彼兩者所連接之氮一起，形成視情況經取代之 队雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次燒某 =直T代之直鏈或分枝狀次缚基鏈或恤 、、二取代之直鏈或分枝狀次炔基鏈；且 ❹枝狀次烯基-直 4.如請求項3之化合物，其中： η為1 ; 128409 200836743 0、. 、^為稠合笨基， Ri為氮； R2為氯或烧基， R3為芳基，視情況被一或多個取代基取代，取代基選自包 括烧基、浠基、快基、鹵基、_烧基、iS稀基、鹵快 基、視情況經取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基快基、_r6_CN、-R6-N02、》R6_C)R^、 -R6-0C(0)R4、-R6-〇S(0)2R4、_R6_c(〇)r4、-R6-C(〇)〇r4 ' -R6 -C(0)N(R4 )R5 ' -R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)OR4、-R6-N(R5)C(0)N(R4)R5、-R6_N(R5)S(0)tR4、 &quot;R6 -N[S(0)t R4 ]2 - -R6 -N(R5 )C(=NR5 )N(R4 )R5 - -R6 -N(R5 )C(=NR5 y N(R4)CN 、 -R6 -N(R5 )C[=NC(0)〇R4 ]-N(R4 )-C(0)0R4 、 -R6-N(R5 )-R7-N(R4 )R5 &gt; -R6-N=C(OR4 )R5 &gt; -R6-N=C(R4 )R5 λ -R6-N(R5)-R6视5、…卻㈣及此卻乂專^，其中各 p係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 128409 -10- 200836743 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之n-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 5·如晴求項4之化合物，其中·· η為1 ; Q 為稠合苯基； R1為氫； R2為氫或烷基； R3為苯基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、鹵基、_烷基、_烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 128409 -11 - 200836743 快基、視情況經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基…R6 -CN…R6 -N〇2…R6 _〇r5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 . -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)〇R4，-R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 . -R6 -N[S(0)t R4 ]2、-R6 _N(R5 )c(=nr5 )n(r4 )r5、_r6 _n(r5 )c(=nr5 )_ N(R4 )CN 、 -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 、 -R6-N(R5&gt;R7-N(R4)R5 . -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 . -R6-N(R5)-R6-〇r5、_R6-S(〇)pR4&amp;_R6_s(〇)tN(R4)R5，其中各 P係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、齒烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 、、、二取代之環烧基烧基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4R5和彼兩者所連接之氮_起，形成視情況經取代之 N雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 ;且 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈 128409 -12- 200836743 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 6.如請求項5之化合物，其中： η為1 ; G、. 為稠合本基， R1為氫； R2為氫或烧基； R3為苯基，視情況被一或多個取代基取代，取代基選自包 括烧基、鹵基、鹵烧基、-R6 -Qs[、-R6 -OR5、-R6 -〇C(0)R4、 -R6 -0S(0)2 R4、-R6 -C(0)0R4、-R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、 -R6 -N(R5 )C(0)R4、-R6 -N(R5 )C(0)〇R4、-R6 _n(R5 )C(0)N(R4 )R5、 -R6 -N[S(0)t R4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、-R6 -N(R5 )C(=NR5)- N(R^)CN ^ -R6-N(R5&gt;R^N(R4)R5 . -R6-N(R5)C[=NC(0)0R4]. N(R4)-C(0)0R4、.R6.N=C(〇R4)r5、.R6.N=C(R4)R5 . -R6-N(R5)-R6-OR5 及 _R6_s(0)tN(R4)R5，其中各 p 係獨立為 〇, 1或2 ’且各t係獨立為i或2 ; 各R4、與R5係獨立選自包括氳、燒基、齒烧基、視情況經取 代之芳基、視情況經取代之雜環基、視情況經取代之 雜環基烷基及視情況經取代之雜芳基； 或R與R和彼兩者所連接之氮一起，形成視情況經取代之 N-雜ί哀基或視情況經取代之N-雜芳基； 各R為直接冑結、視情況經取代之直鏈或分枝狀次院基 鏈、視f青況經取代之直鏈或分枝狀次烯基鏈或視情況 128409 -13- 200836743 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次歸基鍵 &lt; 直 鏈或分枝狀次炔基鏈。 7·如請求項6之化合物，其係選自包括： 2·丁基_3_(4-甲氧苯基 &gt;奎唑啉-4(3H)-酮； 4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯曱醯胺； 2-胺基苯曱酸4-(2-丁基-4-酮基喳唑啉-3(4H)-基）笨g旨； 2- [(1·甲氧基亞戍基）胺基]苯甲酸4-(2-丁基-4-自同基峻α坐琳 ·3(4Η)-基）苯酯； (1Ζ)-Ν-[4-(2-丁基-4-酮基喹唑啉-3(4Η&gt;基）苯基]戊亞胺酸甲 酯； 三氟甲烷磺酸4-(2-丁基-4-酮基喳唑啉-3(4Η)-基）苯酯； 3- (4-胺基苯基）-2-丁基ρ奎嗤ρ林-4(3Η)-酮； 4- (2-丁基-4-酮基喳唑啉-3(4Η)_基）苯磺醯胺； 4·(2-丁基-4-酮基喳唑啉-3(4Η)_基）苯甲酸甲酯； 4-(2·丁基冬酮基喹唑啉-3(4Η)-基）苯甲酸； % 3-(4-漠苯基）-2-丁基7奎吐淋_4(311)-酉同； 3-(3-胺基苯基）-2-丁基峻峻琳-4(3Η)-酮； 1- [4-(2-丁基-4-酮基喹吐啉-3(4Η)-基）苯基]脲； 2- 丁基-3-[4-(甲胺基）苯基]喳唑啉_4(3Η)_酮； 3- (4-胺基苯基）-2-甲基喹唑啉-4(3Η)-酮； 3-(3-胺基苯基）-2-甲基喳唑啉-4(3Η)-酮； 3-(4-胺基苯基）-2-戊基喳唑啉-4(3Η&gt;酮； 3-(4-胺基苯基）-2-丙基峻。坐淋-4(3Η)-酮； 128409 -14- 200836743 2_丁基各[4_(吡啶-2-基胺基）苯基 &gt;奎唑啉-4(3H)-酮； 2- 丁基-3-(4-嗎福啉-4_基苯基 &gt;奎唑啉-4(3H)-酮； 2· 丁基各⑷氟苯基）峻唑啉-4(3H)-酮； 3- (2-胺基苯基）_2·丁基喳唑啉-4(3H)-酮； 1- [4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]胍； 2- 丁基-3-(4-氣苯基）喳唑啉-4(3H)-酮； 1- [4-(2-丁基_4_酮基喳唑啉_3(4H)_基）苯基]-3-氰胍； 3- {[4-(2-丁基_4_酮基喹唑啉-3(4H)-基）苯基]胺基}四氫吡咯小 羧酸第三-丁酯； 2- 丁基-3·[4-(四氫ρ比洛-3-基胺基）苯基]峻峻琳-4(3H)-酮； 2-丁基_3-(4-{[2-(二甲胺基）乙基]胺基}苯基）邊唑啉-4(3H)-酮； 2-丁基-3-[4-(4-甲基六氯ρ比17井-1-基）苯基]p奎唾p林-4(3H)-闕； 2- 丁基-3-(4-六氫外匕_ -1-基苯基）峻。坐琳-4(3H)-_ ; 3- (4-胺基-2,5-二甲基苯基）-2-丁基喹唑啉-4(3H)-酮； 3- (4-胺基苯基）-2-乙基喹唑啉·4(3Η)_酮； 4- (2-丁基-4-酮基喹唑啉-3(4Η)-基）苯甲腈； 3-(4-胺基-2,3,5,6-四甲基苯基）-2-丁基喳唑啉-4(3Η)-酮； 3-(4-胺基-2,5-二氣苯基）-2-丁基喳唑啉-4(3Η)-酮； 3-(4-溴基-2-氟苯基）-2-丁基喳唑啉-4(3Η)-酮； 3-[4·(胺基甲基）苯基]-2-丁基喳唑啉-4(3Η)-酮； [4-(2•丁基-4-酮基喳唑啉-3(4Η)-基）苄基]胺基甲酸第三_丁酯； 3-(4-溴基-2-氣苯基）-2-丁基喳唑啉-4(3Η)-酮； 3-[4-漠基-2-(三氟甲基）苯基]-2-丁基ρ奎嗤ρ林-4(3H)-g同； 3-(4-溴基-2,6-二氟苯基）·2-丁基喳唑啉-4(3H)-_ ; 128409 -15- 200836743 3-(4-漠基-2_甲基苯基）·2-丁基p套嗤琳-4(3H)-酮； 3-(4•漠基-2,6-二甲基苯基）-2-丁基π奎嗤琳-4(3H)-酮； 2-丁基-3-(2-氣基-4-嗎福琳-4-基苯基奎a坐琳-4(3H)-嗣； 2-丁基-3-[4-嗎福啉冬基-2_(三氟曱基）苯基]喹唑啉-4(3H)-酮； 2-丁基-3-(2,6-二氟*4·嗎福琳-4-基苯基 &gt;奎峻琳-4(3H)-酮； 2-丁基-3-(2-甲基-4-嗎福淋-4-基苯基）峻a坐p林-4(3H)-酮； 2-丁基-3-(2,6-二甲基-4-嗎福淋-4-基苯基）峻唆琳-4(311)-8同； 2-丁基-3-(2-氟基-4-嗎福p林-4-基苯基 &gt;奎唾琳-4(3H)-酮； 2-丁基-3-(4-六鼠批咬-1-基苯基）pr奎σ坐p林-4(3H)-嗣； 2- 丁基-3·[4-(六氫ρ比咬-3-基胺基）苯基]p奎嗤琳-4(3H)-酮； 3- [4-胺基-3-(三氟曱基）苯基]-2-丁基ρ奎唾琳-4(3H)-酮； 3-[4-胺基-2-(三氟曱基）苯基]-2-丁基峻哇琳-4(3H)-酮； 2-丁基-3-{4-[(2·羥基-3-苯氧基丙基）胺基]苯基}喹唑啉-4(3H)· 酮； 2-丁基-3-{4-[2-(苯氧基甲基）嗎福啉冰基]苯基}喹唑啉-4(3H)- 酮； 2-丁基-3_(4-{[(2,2-二甲基-1，3-二氧伍圜冰基）甲基]胺基}苯基） 口奎唾淋-4(3H)-酮； 2- 丁基-3-{4_[(2,3-二經基丙基）胺基]苯基}峻。坐琳-4(3H)-酮； N-[4-(2-丁基-4-酮基喹唑啉_3(4H&gt;基）苯基]甲烷磺醯胺； N-[4-(2-丁基-4-酮基喹唑啉-3(4H)-基）苯基]乙醯胺； N-[4-(2_丁基-4-酮基喳唑啉-3(4H&gt;基）苯基]-N-(甲磺醯基）甲烷 磺醯胺； 3- [4-( —氮四圜-3-基胺基）苯基]-2-丁基p奎唾p林-4(3H)-酮鹽酸 128409 -16- 200836743 鹽； 2-丁基-3-{4-[(7aS)-3-酮基四氫-1H-吡咯并[l，2-c]咪唑-2(3H)-基] 苯基奎吐1(7林-4(3H)-嗣； 2-丁基-3-{4-[(3R)-六氫吡啶-3-基胺基]苯基}喳唑啉-4(3H)-酮鹽 酸鹽； 2- 丁基各[4-(四氫吡咯-3-基氧基）苯基]喹唑啉·4(3Η)_酮二鹽 酸鹽； 3- 丁基·2-[4-(四氫吡咯-3-基胺基）苯基]喳唑啉-4(3Η)-酮鹽酸 鹽； (R) -2-丁基-3-(4-(四氫吡咯-3-基胺基）苯基）喹唑啉-4(3Η)-酮；及 (S) -2· 丁基-3-(4-(四氫吡咯-3-基胺基）苯基）喹唑啉-4(3Η)-酮鹽 酸鹽。 8.如請求項6之化合物，其係選自包括： 2-丁基_3-(4-羥苯基）喹唑啉-4(3Η)-酮； 2-丁基-3·{4-[(二本亞甲基）胺基]苯基奎嗤淋-4(3Η)-酮； [4-(2·丁基-4-酮基喹唑啉-3(4Η)·基）苯基]胺基甲酸第三_丁酯； [4-(4-酮基-2-丙基喹唑啉-3(4Η)-基）苯基]胺基甲酸第三-丁酯； [4-(2-乙基-4-酮基喹唑啉-3(4Η)-基）苯基]胺基甲酸第三_丁酯； [4-(2· 丁基冰酮基喳唑啉-3(4Η)-基）苯基]甲基胺基甲酸第三· 丁醋； [2-(2-丁基-4-酮基喹唑啉-3(4Η)·基）苯基]胺基甲酸第三_丁酯； [4-(2-丁基-4-酮基喳唑啉-3(4Η)_基）-3-(三氟甲基）苯基]胺基甲 酸第三-丁酯； [(弟二-丁氧幾基）胺基]{[4-(2-丁基-4-S同基峻哇淋-3(4H)-基）苯 128409 -17- 200836743 基]胺基}亞甲基]胺基甲酸第三丁酯； [4_(2_丁基-4-酮基喹唑啉-3(4H)·基）爷基]胺基甲酸第三-丁酯； [4-(2-丁基-4-酮基喳唑啉-3(4H)-基）_2-(三氟甲基）苯基]胺基甲 酸第三-丁酯； 4-[4-(2-丁基-4-酮基喳唑啉-3(4H)-基）苯基]六氫吡畊-1-羧酸第 三-丁酯； 3-{[4-(2-丁基-4-酮基喹唑啉-3(4H)_基）苯基]胺基}六氫吡啶-1-羧酸第三-丁酯； 3-{[4_(2-丁基-4-酮基喳唑啉·3(4Η)_基）苯基]胺基}一氮四圜-1-羧酸第三-丁酯； (3R)-3-{[4-(2-丁基-4-酮基喳。坐啉-3(4Η)-基）苯基]胺基}六氫吡 σ定-1-魏酸第三-丁醋， 3-[4-(2•丁基-4·酮基喳唑啉-3(4Η)·基）苯氧基]四氫吡咯-1-羧酸 第三-丁酯； 2_(4_溴苯基）-3-丁基喳唑啉-4(3Η)-酮； 3-(4-(3_丁基-4-酮基-3,4-二氫喹唑啉-2-基）苯基胺基）四氫吡咯 -1-羧酸第三-丁酯； (R) -3-(4-(2-丁基-4-嗣基峻唆淋-3(4Η)-基）苯基胺基）四氮ρ比π各 -1-羧酸第三-丁酯；及 (S) -3-(4-(2-丁基-4-酮基ρ奎。坐琳-3(4Η)_基）苯基胺基）四氯p比洛小 羧酸第三-丁酯。 9.如請求項4之化合物，其中： η為1 ; 128409 -18 - 200836743 G、. 為稠合笨基； R1為氫； R2為氫或烷基； R為奈基’視情況被_或多個取代基取代，取代基選自包 括烷基、烯基、炔基、齒基、i烷基、㈣基、齒炔 土視^況、、、工取代之環烷基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 %烧基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視h況經取代之芳烯基、視情況經取代之芳 炔基視彳肖况經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、_R6_C]Si、_r6_n〇2、&quot;R6-〇R5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 - -R6-C(0)R4 - -R6-C(0)0R4 --R6 -C(0)N(R4 )R5、-R6-N(R4)R5 ^ -R6-N(R5 )C(0)R4 -R6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6_N(R5)s(〇)tR4、 •R6 -N[S(0)t R4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、_R6 -N(R5 )c(=nr5 N(R4)CN、_R6-N(R5)C[=NC⑼OR4]_&gt;C R7 -N(R4 )R5 &gt; -R6 -N=C(OR4 )R5 ^ -R6 -N=C(R4 )R^ &gt; .r6 .N=C(R4 )R5 、-R6-N(R5)-R6-OR5、-R6-S(0)pR4 及-R6_s(〇)tN(R4)R5，其中 各p係獨立為0, 1或2，且各t係獨立為丨或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 128409 -19- 200836743 況 況 況經 羥烷基、烷氧烷基、視情況經取代之環烷基、視情 經取代之環烷基烷基、視情況經取代之芳基、視= 經取代之芳烷基、視情況經取代之雜環基、視情 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基；Wherein: η is 1 to 4; Q is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, yl, haloalkyl, i-alkenyl, Tetraalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl ,heterocyclylalkenyl,heterocyclylalkynyl,heteroaryl,heteroarylalkyl 'heteroarylalkenyl,heteroarylalkynyl, _R6_CN, &quot;R6-N〇2 &gt; . .R6.N (R4)R5 λ .R6.S(〇)pR4 , .R6 .C(〇)R4 , -R6 -C(S)R4, -R6 -C(r4 )2 C(〇)r5, -R6 _C( 〇)〇R4, _r6 -〇c(〇)R4, -R6 -C(S)OR4 , -R6 -C(0)N(R4 )R5 , -R6 -C(S)N(R4 )R5 , &quot ;R6-N(R5 )C(0)R4 ^ -R6-N(R5 )C(S)R4 ^ -R6-N(R5 )C(0)0R4 ^ -R6-N(R5)C(S) OR4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)C(S)-N(R4)R5, _R6 -N(R5)S(0)t R4, _R6 - N(R5)S(0)tN(R4)R5, -R6 -S(0)tN(R4)R5, -R6 -N(R5)C〇=NR5)N(R4)R5 and _ R6 - N(R5)_ C(N=C(R4)R5)N(R4)R5, wherein each p-system is independently 0, i or 2, and each t-system is independently 1 or 2; or two adjacent R1 group and their Connected carbon or heteroatoms - 128409 200836743 to form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl, and the remaining R1 groups, if present, are as described above; R2 Is hydrogen, alkyl, alkenyl, alkynyl, _alkyl, alkenyl, ethynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aralkenyl , aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R is Hydrogen, alkyl, mercapto, alkynyl, haloalkyl, haloalkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl Alkyl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroaralkyl, heteroarylalkenyl , heteroarylalkynyl, -R7-N(R4)R5 or -R7-n(r4)c(o)or4; wherein cycloalkyl, cycloalkyl, cycloalkylenyl'cycloalkylene Base, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocycle Alkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl may be optionally substituted by one or more substituents selected from alkyl, alkenyl Alkyl, alkynyl, halo, haloalkyl, haloalkenyl, ynkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl Substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted alkynyl, optionally as appropriate Substituted heterocyclic group, optionally substituted heterocyclylalkyl, 128409 200836743 optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, Optionally substituted heteroaryl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, &quot;R6 -0C(0)R4 . -R6-0S(0)2R4 ^ -R6-C(0)R4 ^ -R6-C(0)0R4 . -R6 -C(0)N(R4 )R5,-R6 - N(R4)R5, -R6 -N(R5)C(0)R4, -R6-N(R5)C(0)〇R4 -R6-N(R5)C(0)N(R4)R5 &gt;-R6-N(R5&gt; S(〇)tR4 . -R6-N[S(0)tR4]2 ^ -R6-N( R5)C(=NR5)N(R4)R5 . -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4].N (R4&gt; C(0)〇R4 . -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 -R6-N(R5)-R6-OR5, -r6-s(o)pr4 and HS(0)tN(R4)R5, wherein each p-system is independently 〇, i or 2, and each t-system is independently 1 Or 2; each R and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, dentate alkyl, alkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted Cycloalkylalkyl, optionally substituted aryl, optionally, disubstituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted a heteroaryl group and optionally substituted heteroaralkyl; , /, R together with the nitrogen to which they are attached, form optionally substituted heterocyclic groups or optionally substituted heteroaryl groups; Han 6 is a direct-bonded, optionally substituted linear or branched alkylene chain, optionally substituted linear or branched olefin a chain or, as appropriate, a disubstituted linear or branched secondary block chain; and 128409 200836743 R7 is a linear or branched subalkyl chain, a linear or branched subalkenyl chain or a straight bond Or a branched hypoalkynyl chain; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 2. The compound of claim 1, wherein η is 1 to 4; Q is a fused aryl group; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, dentyl, haloalkyl, Ialkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, hetero Cycloalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl 'heteroarylalkenyl, heteroarylalkynyl, _R6_CN, -R6-N〇2, -R6 _〇R5, _R6 collar R4)R5, -R6-S(〇)pR4, r6 _c(〇)r4, -R6-C(S)R4 &gt; -R6-C(R4)2 C(0)R5 - -R6-C(0)〇R4 - -R6-〇C(0)R4 ^ -R6 -C(S)OR4, -R6 -C(0)N(R4 )R5,_R6 -C(S)N( R4)R5, -R6-N(R5)C(0)R4, -R6-N(R5)C(S)R4, -R6-N(R5)c(〇)〇R4, -R6-N(R5 C(S)OR4, -R6-N(R5)C(0)N(R4)R5, -R6_N(R5)C(s)-N(R4)R5, HN(R5)S(〇)tR4, _r6-N(r5)s(〇xn(r4)r5, •R6 -S(0)tN(R4)R5, -R6 -N(R5)C(=NR5 )N(R4 )R5 and -R6-N (R5)C(N=C(R4)R5)N(R4)R5, wherein each p is independently 〇, 1 or 2, and each t is independently 1 or 2; or two adjacent R1 groups and They are straight The attached carbon ring atoms together form a fused ring selected from cycloalkyl, aryl, heterocyclic or heteroaryl groups, 128409 200836743 and the remaining R1 groups, if present, are as described above; R2 is hydrogen, alkane Base, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aryl, alkynyl , heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is hydrogen, alkyl , alkenyl, alkynyl, haloalkyl, alkenyl, ynkynyl, oxadialkyl, cycloalkyl, cycloalkyl, cycloalkylene, cycloalkylenyl, aryl, aromatic Anthracenyl, aralkenyl, arylalkynyl, heterocyclyl, heteroenylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroaryl Alkynyl, _R7_N(R4)R5 or -R7-n(r4)c(o)or4; wherein cycloalkyl, cycloalkylalkyl, cycloalkyl, cycloalkyl, aryl, aryl Alkyl, aralkenyl, arylalkynyl, heterocyclic, heterocyclylalkyl, heterocyclic An alkenyl group, a heterocyclyl alkynyl group, a heteroaryl group, a heteroarylalkyl group, a heteroarylalkenyl group or a heteroarylalkynyl group may be optionally substituted by one or more substituents. The substituent is selected from the group consisting of an alkyl group and a dilute group. , alkynyl, .syl, haloalkyl, alkenyl, alkynyl, optionally substituted cycloalkane t, optionally substituted cycloalkylalkyl, optionally substituted, alkyl thiol, Substituted cycloalkylenyl, optionally substituted aryl, optionally substituted aryl, optionally, substituted (tetra), optionally substituted alkynyl, as appropriate Substituted m-ring group, optionally substituted heterocyclic alkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclic ring 128409 200836743 alkynyl group, optionally substituted heteroaryl group, Substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, -R6-oc (o) R4, -R6-〇s(o)2R4, -R6-C(0)R4, -R6-C(0)0R4, -R6-c(〇)N(R4)R5, _r6-n( R4)r5, _r6-n(r5)c(0)r4, -R6-N(R5)C(0)0R4^-R6-N(R5)C(0)N(R4)R5 &Gt-R6-N(R5&gt; S(0)tR4, -R6_N[S(0)tR4]2, -R6_n(r5)c(=nr5)n(r4)r5 '-R6-N(R5)C (=NR5)N(R4)CN &gt;-R6-N(R5)C[=NC(0)0R4].N(R4&gt; C(〇)〇r4 &gt; -R6-N(R5)-R7- N(R4)R5 . -R6-N=C(OR4)R5 . -R6 -N=C(R4 )R5, -R6 -N(R5 )-R6 _0R5, -R6 _S(0)p R4 and -R6 -S(0)tN(R4)R5, wherein each p is independently 〇, i or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, Alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted Alkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 and R5(d) The nitrogen is formed by the N-heteroyl group which is substituted as the case may be, or the group which is replaced by the case, and each R6 is a direct-bonded or optionally substituted linear or branched secondary alkyl chain. a direct bond or a branched sub-alkenyl chain, as appropriate, or as appropriate The secondary linear or branched alkynyl chain; and W is a straight-chain or branched: under-firing group, straight chain or branched group iv bond or a straight-chain or branched 128,409,200,836,743 times alkynyl chain. 3. The compound of claim 2, wherein: η is 1 to 4; G, is a chelating base, and each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, yl, haloalkyl , i alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, Heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroaryl, heteroaryl, heteroaryl, _r6_Cn, -R6-N〇2 - -R6 -〇R5 &gt; -R6-N(R4)R5 &gt; -R6-S(0)pR4 &gt; -R6-C(0)R4 &gt; -R6-C(S)R4, -R6-C(R4 ) 2c(0)r5, _r6_c(〇)〇r4, _r6 〇c(〇)r4, -R6-C(S)OR4, -R6-C(0)N(R4)R5, -R6 -c(5)N(R4 )r5, -R6-N(R5)C(0)R4, -R6-N(R5)C(S)R4, -R6_N(R5)c(〇)〇R4, -R6-n(r5)c( s)or4, -r6-n(r5)c(o)n(r4)r5, -R6_n(R5)c(s)_ N(R4)r5, _R6 -N(R5)S(0)t R4, -R6 -N(R5 )s(0)t N(R4 )R5, -R6 -S(0)t N(R4 )R5, -R6 -N(R5 )C(=NR5 )N(R4 )R5 and -R6 _N(R5 )C(N= 〇 4 4 瓜 5, say 4, 5, where each p is independently 〇, 1 or 2, and each ^ is independently 1 or 2; or two adjacent R1 groups Group and Together with the directly attached carbon ring atoms, a fused ring may be formed, selected from cycloalkyl, aryl, heterocyclyl or heteroaryl, and the remaining R1 groups, if present, are as described above; R2 is hydrogen , alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkyl, cycloalkyl, aryl, aryl, 128409 200836743 aralkenyl , aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is Hydrogen, alkyl, alkenyl, alkynyl, _alkyl, alkenyl, alkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkyl fast radical, aromatic Alkyl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl , heteroarylalkynyl, _R7_N(R4)R5 or -r7-n(r4)c(o)or4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl Base, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl The heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl groups. , alkenyl, alkynyl, yl, halo, (iv)yl 4, cyclyl optionally substituted, optionally substituted cycloalkyl, optionally substituted cycloalkylene Substituted (IV), as appropriate, aralkyl group, aryl group substituted as appropriate, optionally substituted aryl group, optionally substituted aryl group, optionally substituted a heterocyclic group, optionally substituted heterocyclic alkyl group, optionally a heterocyclic alkynyl group, optionally a heterocyclic alkynyl group, optionally substituted heteroaryl group, optionally substituted Substituted W-block bases, _r6_cn, _r 128409 200836743 -r6-oc(o)r4, -R6-〇S(〇)2R4, -R6-C(0) R4, -R6-C(0)0R4, -R6-C(0)N(R4)R5, -R6-N(R4)R5, -r6-n(r5)c(o)r4, -R6-N (R5)C(0)OR4, -R6-N(R5)C(0)N(R4)R5, -R6-N(R5)S(0)tR4, -R6 -N[S(0)t R4 ]2, -R6-N( R5)C(=NR5)N(R4)R5, -r6-N(R5)C(=NR5)N(R4)CN, -R6 -N(R5)C[=NC(Q)OR4 ]-N( R4)-C(0)OR4, -R6-N(R5&gt;R7-N(R4)R5^-R6-N=C(OR4)R5 - -R6-N=C(R4)R5 &gt; -R6 - N(R5)-R6-〇R5, -R6-S(〇)p R4 and -R6 n(r4)r5, wherein each p-system is independently 〇, 1 or 2, and each t-series is independently 1 or 2; Each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl. Alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted a substituted heteroarylalkyl group; or R4 and R: together with the nitrogen to which they are attached, form an optionally substituted heterocyclic group or an optionally substituted N-heteroaryl; each R6 is directly Bonded, optionally substituted linear or branched sub-sinter = straight or branched sub-chain or t-shirt, di-substituted linear or branched sub-alkynyl chain; And lychee-like alkenyl-straight 4. as requested The compound of Item 3, wherein: η is 1; 128409 200836743 0, . , ^ is a fused base, Ri is nitrogen; R 2 is chloro or alkyl, R 3 is aryl, optionally substituted by one or more substituents a substituent selected from the group consisting of an alkyl group, a fluorenyl group, a fast group, a halogen group, a decyl group, an iS group, a halogen group, an optionally substituted cycloalkyl group, optionally substituted cycloalkylalkyl group, Optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally as appropriate Substituted aralkynyl, optionally substituted heterocyclic, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, Substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryl, _r6_CN, -R6-N02, "R6_C" R^, -R6-0C(0)R4, -R6-〇S(0)2R4, _R6_c(〇)r4, -R6-C(〇)〇r4 ' -R6 -C(0)N(R4 )R5 ' -R6 -N(R4 )R5, -R6 -N(R 5) C(0)R4, -R6-N(R5)C(0)OR4, -R6-N(R5)C(0)N(R4)R5, -R6_N(R5)S(0)tR4, &quot ; R6 -N[S(0)t R4 ]2 - -R6 -N(R5 )C(=NR5 )N(R4 )R5 - -R6 -N(R5 )C(=NR5 y N(R4)CN , -R6 -N(R5 )C[=NC(0)〇R4 ]-N(R4 )-C(0)0R4 , -R6-N(R5 )-R7-N(R4 )R5 &gt; -R6-N =C(OR4)R5 &gt; -R6-N=C(R4)R5 λ -R6-N(R5)-R6 视5,...but (4) and this 乂 乂 ^, where each p is independent 〇, 1 Or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, 128409 -10- 200836743 hydroxyalkyl, alkoxyalkyl , optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally Substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-hetero a cyclic group or an optionally substituted n-heteroaryl; each R6 is a direct-bonded, optionally substituted linear or branched alkylene group a linear or branched sub-alkenyl chain or a linear or branched nalynyl chain optionally substituted; and R is a linear or branched alkylene chain, linear or A branched secondary alkenyl chain or a linear or branched subalkynyl chain. 5. A compound according to item 4, wherein η is 1; Q is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or alkyl; R3 is phenyl, optionally substituted by one or more substituents. a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, halo, _alkyl, alkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, Optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally as appropriate Substituted aryl 128409 -11 - 200836743 Fast-rading, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclic ring Alkynyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl...R6-CN...R6 -N〇2...R6 _〇r5, -R6-0C(0)R4 &gt; -R6-0S(0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 . -R6 -C(0)N(R4)R5, -R6 -N(R4)R 5, -R6 -N(R5)C(0)R4, -R6-N(R5)C(0)〇R4,-R6-N(R5)C(0)N(R4)R5 &gt; -R6- N(R5)S(0)tR4 . -R6 -N[S(0)t R4 ]2, -R6 _N(R5 )c(=nr5 )n(r4 )r5, _r6 _n(r5 )c(=nr5 )_N(R4 )CN , -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 , -R6-N(R5&gt;R7-N(R4)R5 -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 . -R6-N(R5)-R6-〇r5, _R6-S(〇)pR4&_R6_s(〇)tN (R4) R5, wherein each P is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and alkenyl , hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally, disubstituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, Optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4R5 and the nitrogen to which they are attached _ Forming optionally substituted N heterocyclic groups or optionally substituted heteroaryl groups; each R6 is a direct-bonded, optionally substituted linear or branched alkylene group; a linear or branched subalkenyl chain, or optionally substituted linear or branched subalkynyl chain, 128409 -12-200836743 R7 is a linear or branched alkyl chain a linear or branched subalkenyl chain or a linear or branched subalkynyl chain. 6. The compound of claim 5, wherein: η is 1; G, is a fused radical, R1 is hydrogen; R2 is hydrogen or alkyl; R3 is phenyl, optionally substituted by one or more substituents. The substituent is selected from the group consisting of an alkyl group, a halogen group, a halogen group, -R6-Qs[, -R6-OR5, -R6-〇C(0)R4, -R6-0S(0)2 R4, -R6- C(0)0R4, -R6 -C(0)N(R4)R5, -R6 -N(R4)R5, -R6 -N(R5)C(0)R4, -R6 -N(R5)C( 0) 〇R4, -R6 _n(R5)C(0)N(R4)R5, -R6 -N[S(0)t R4 ]2, -R6 -N(R5 )C(=NR5 )N(R4 R5, -R6 - N(R5)C(=NR5)- N(R^)CN ^ -R6-N(R5&gt;R^N(R4)R5 . -R6-N(R5)C[=NC( 0)0R4]. N(R4)-C(0)0R4, .R6.N=C(〇R4)r5,.R6.N=C(R4)R5 . -R6-N(R5)-R6-OR5 And _R6_s(0)tN(R4)R5, wherein each p is independently 〇, 1 or 2' and each t is independently i or 2; each R4, and R5 are independently selected from the group consisting of ruthenium, ruthenium, and tooth An alkyl group, optionally substituted aryl group, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl group, and optionally substituted heteroaryl group; or R and R and both Together with the nitrogen, form an N-heterolyzed group that is substituted as appropriate or N-substituted as appropriate Aryl; each R is a direct oxime, a linear or branched sub-base chain that is optionally substituted, or a linear or branched sub-alkenyl chain substituted by the condition or as appropriate 128409 -13- 200836743 Substituted linear or branched subalkynyl chain; and R7 is a linear or branched alkylene chain, a linear or branched sub-base bond &lt; linear or branched hypoalkynyl 7. The compound of claim 6 which is selected from the group consisting of: 2·butyl-3-(4-methoxyphenyl) quinazoline-4(3H)-one; 4-(2-butyl 4-ketoquinazoline-3(4H)-yl)benzamide; 2-aminobenzoic acid 4-(2-butyl-4-ketooxazoline-3(4H)-yl Stupid; 2-[(1. methoxyindenyl)amino]benzoic acid 4-(2-butyl-4-carboyl-α-azate-3(4Η)-yl)phenyl ester (1Ζ)-Ν-[4-(2-butyl-4-ketoquinazolin-3(4Η&gt;yl)phenyl]pentaminate; 4-trifluoromethanesulfonic acid 4-(2- Butyl-4-ketooxazoline-3(4Η)-yl)phenyl ester; 3-(4-aminophenyl)-2-butyl ρ 奎嗤ρ林-4(3Η)-one; 4 - (2-butyl-4-ketooxazoline-3(4Η)-yl)benzenesulfonamide; 4·(2-butyl-4-ketooxazoline-3 (4 Η) _ base) methyl benzoate; 4-(2·butylbutanyl quinazolin-3(4Η)-yl)benzoic acid; % 3-(4-diphenyl)-2-butyl 7奎吐淋_4(311)-酉同; 3-(3-Aminophenyl)-2-butyljunjun-4(3Η)-one; 1-[4-(2-butyl-4-one) 5-quinoline-3(4Η)-yl)phenyl]urea; 2-butyl-3-[4-(methylamino)phenyl]oxazoline-4(3Η)-one; 3- (4 -aminophenyl)-2-methylquinazoline-4(3Η)-one; 3-(3-aminophenyl)-2-methyloxazoline-4(3Η)-one; 3- (4-Aminophenyl)-2-pentyloxazoline-4 (3Η&gt;ketone; 3-(4-aminophenyl)-2-propyl jun.坐-4 (3Η)-ketone; 128409 -14- 200836743 2_butyl each [4_(pyridin-2-ylamino)phenyl&gt;quinazoline-4(3H)-one; 2-butyl -3-(4-morpholin-4-ylphenyl)&gt;quinazoline-4(3H)-one;2·butyl(4)fluorophenyl)trazoline-4(3H)-one;-(2-Aminophenyl)_2.butyloxazoline-4(3H)-one; 1-[4-(2-butyl-4-ketoquinazolin-3(4H)-yl) Phenyl]anthracene; 2-butyl-3-(4-phenylphenyl)oxazoline-4(3H)-one; 1-[4-(2-butyl-4-yl-oxazoline-3 (4H)-yl)phenyl]-3-cyanoguanidine; 3-{[4-(2-butyl-4-yl)quinazolin-3(4H)-yl)phenyl]amino}tetrahydro Pyrrole small carboxylic acid tert-butyl ester; 2-butyl-3·[4-(tetrahydroρylo-3-ylamino)phenyl]junjun-4(3H)-one; 2-butyl 3-3-(4-{[2-(Dimethylamino)ethyl]amino}phenyl)oxazoline-4(3H)-one; 2-butyl-3-[4-(4- Methyl hexachloro-p-ratio 17 well-1-yl)phenyl]p-quino-p-lin-4(3H)-indole; 2-butyl-3-(4-hexahydroexo- -1-ylphenyl) ) Jun.坐琳-4(3H)-_ ; 3-(4-Amino-2,5-dimethylphenyl)-2-butylquinazolin-4(3H)-one; 3-(4-amine Phenyl)-2-ethylquinazoline·4(3Η)-one; 4-(2-butyl-4-ketoquinazolin-3(4Η)-yl)benzonitrile; 3-( 4-amino-2,3,5,6-tetramethylphenyl)-2-butyloxazoline-4(3Η)-one; 3-(4-amino-2,5-dibenzene 2-(2-butyloxazoline-4(3Η)-one; 3-(4-bromo-2-fluorophenyl)-2-butyloxazoline-4(3Η)-one; 3- [4. (Aminomethyl)phenyl]-2-butyloxazoline-4(3Η)-one; [4-(2•butyl-4-ketooxazoline-3(4Η)- Benzyl]aminocarbamic acid tert-butyl ester; 3-(4-bromo-2-oxophenyl)-2-butyloxazoline-4(3Η)-one; 3-[4- Benzyl-2-(trifluoromethyl)phenyl]-2-butyl ρ 嗤 嗤 林 林 - 4 (3H)-g with the same; 3-(4-bromo-2,6-difluorophenyl) 2-butyloxazoline-4(3H)-_ ; 128409 -15- 200836743 3-(4-Molyl-2-methylphenyl)·2-butyl p-set 嗤琳-4(3H)- Ketone; 3-(4•glycine-2,6-dimethylphenyl)-2-butyl π-quineline-4(3H)-one; 2-butyl-3-(2-carbyl- 4-fofolin-4-ylphenyl quinone a sitin-4(3H)-oxime; 2-butyl-3-[4-morpholinoline-2_( Trifluoromethyl)phenyl]quinazolin-4(3H)-one; 2-butyl-3-(2,6-difluoro*4·fofolin-4-ylphenyl) 奎奎琳-4(3H)-keto; 2-butyl-3-(2-methyl-4-moffa-4-ylphenyl) Juna sitting p-lin-4(3H)-one; 2-butyl -3-(2,6-dimethyl-4-norfos-4-ylphenyl) Junyulin-4(311)-8 with; 2-butyl-3-(2-fluoro-4) - 福福普林-4-ylphenyl&gt;Quiniumline-4(3H)-one; 2-butyl-3-(4-six-biten-1-ylphenyl)pr-σ Lin-4(3H)-oxime; 2-butyl-3·[4-(hexahydrop-buty-3-ylamino)phenyl]p-quineline-4(3H)-one; 3- [ 4-amino-3-(trifluoromethyl)phenyl]-2-butyl quinquinine-4(3H)-one; 3-[4-amino-2-(trifluoromethyl)benzene 2-butylwanowin-4(3H)-one; 2-butyl-3-{4-[(2.hydroxy-3-phenoxypropyl)amino]phenyl}quinazoline- 4(3H)·ketone; 2-butyl-3-{4-[2-(phenoxymethyl)morpholine yl]phenyl}quinazoline-4(3H)-one; 2-butyl -3-(4-{[(2,2-dimethyl-1,3-dioxosulfanyl)methyl]amino}phenyl) phenquinidine-4(3H)-one; 2 - Butyl-3-{4_[(2,3-dipropylpropyl)amino]phenyl}.琳琳-4(3H)-one; N-[4-(2-butyl-4-ketoquinazolin-3(4H&gt;yl)phenyl]methanesulfonamide; N-[4-(2 -butyl-4-ketoquinazolin-3(4H)-yl)phenyl]acetamide; N-[4-(2-butyl-4-ketooxazoline-3 (4H&gt;) Phenyl]-N-(methylsulfonyl)methanesulfonamide; 3-[4-(-azatetraindole-3-ylamino)phenyl]-2-butyl p-quinegrin-p--4 (3H)-ketohydrochloride 128409 -16- 200836743 salt; 2-butyl-3-{4-[(7aS)-3-ketotetrahydro-1H-pyrrolo[l,2-c]imidazole-2 ( 3H)-yl]phenyl quinone 1 (7-lin-4(3H)-oxime; 2-butyl-3-{4-[(3R)-hexahydropyridin-3-ylamino]phenyl}anthracene Oxazoline-4(3H)-one hydrochloride; 2-butyl[4-(tetrahydropyrrol-3-yloxy)phenyl]quinazoline·4(3Η)-one dihydrochloride; 3-butyl 2-[4-(tetrahydropyrrol-3-ylamino)phenyl]oxazoline-4(3Η)-one hydrochloride; (R)-2-butyl-3-( 4-(tetrahydropyrrol-3-ylamino)phenyl)quinazolin-4(3Η)-one; and (S)-2·butyl-3-(4-(tetrahydropyrrol-3-yl) Amino)phenyl)quinazolin-4(3Η)-one hydrochloride. 8. A compound according to claim 6 which is selected from the group consisting of: 2-butyl-3-(4-hydroxyphenyl)quina Azole Porphyrin-4(3Η)-one; 2-butyl-3·{4-[(dibenzylidene)amino]phenylquinidine--4(3Η)-one; [4-(2·丁4--4-ketoquinazoline-3(4Η)-yl)phenyl]carbamic acid tert-butyl ester; [4-(4-keto-2-propylquinazoline-3(4Η) -Phenyl]phenyl]carbamic acid tert-butyl ester; [4-(2-ethyl-4-ketoquinazolin-3(4Η)-yl)phenyl]carbamic acid tert-butyl ester [4-(2·butyl keto keto oxazoline-3(4Η)-yl)phenyl]methylaminocarboxylic acid third · butyl vinegar; [2-(2-butyl-4-keto) Quinazoline-3(4Η)·yl)phenyl]carbamic acid tert-butyl ester; [4-(2-butyl-4-ketooxazoline-3(4Η)-yl)-3- (trifluoromethyl)phenyl]carbamic acid tert-butyl ester; [(di-butoxymethyl)amino]{[4-(2-butyl-4-S) 3(4H)-yl)benzene 128409 -17- 200836743 yl]amino}methylene]carbamic acid tert-butyl ester; [4_(2_butyl-4-ketoquinazolin-3(4H)) · ) ] ] 胺 胺 胺 胺 胺 胺 胺 [ [4-(2-butyl-4-ketooxazoline-3(4H)-yl)_2-(trifluoromethyl)phenyl] Tert-butyl carbamic acid; 4-[4-(2-butyl-4-ketooxazoline-3(4H)-yl)phenyl]hexahydro Pyridin-1-carboxylic acid tert-butyl ester; 3-{[4-(2-butyl-4-ketoquinazolin-3(4H)-yl)phenyl]amino}hexahydropyridine- 1-carboxylic acid tert-butyl ester; 3-{[4_(2-butyl-4-ketooxazoline·3(4Η)-yl)phenyl]amino}mononitrotetradec-1-carboxylate Acidic third-butyl ester; (3R)-3-{[4-(2-butyl-4-ketoindole). Cyclosporin-3(4Η)-yl)phenyl]amino}hexahydropyridinium-1-weilic acid tert-butyl vinegar, 3-[4-(2•butyl-4·ketooxazoline) -3(4Η)·yl)phenoxy]tetrahydropyrrole-1-carboxylic acid tert-butyl ester; 2-(4-bromophenyl)-3-butyloxazoline-4(3Η)-one; 3-(4-(3-butyl-4-keto-3,4-dihydroquinazolin-2-yl)phenylamino)tetrahydropyrrole-1-carboxylic acid tert-butyl ester; R) -3-(4-(2-butyl-4-fluorenylphosphonium-3(4Η)-yl)phenylamino)tetrazo-ρ ratio to π-l-carboxylic acid tert-butyl ester ; and (S) -3-(4-(2-butyl-4-keto-p-quine. sitin-3(4Η)-yl)phenylamino)tetrachloro-p-pyrrolic acid carboxylic acid third- Butyl ester. 9. The compound of claim 4, wherein: η is 1; 128409 -18 - 200836743 G, is a fused base; R1 is hydrogen; R2 is hydrogen or alkyl; R is a naphthyl group _ or Substituted by a plurality of substituents selected from the group consisting of alkyl, alkenyl, alkynyl, dentate, i-alkyl, (tetra), ortho-alkyne, cycloalkyl, substituted, optionally substituted Cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted alkylalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, as appropriate Substituted aralkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally Substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_C ]Si, _r6_n〇2, &quot;R6-〇R5, -R6-0C(0)R4 &gt; -R6-0S(0)2R4 - -R6-C(0)R4 - -R6-C(0)0R4 --R6 -C(0)N(R4)R5, -R6-N(R4)R5 ^ -R 6-N(R5 )C(0)R4 -R6-N(R5)C(0)0R4, -R6-N(R5)C(0)N(R4)R5, -R6_N(R5)s(〇) tR4, •R6 -N[S(0)t R4 ]2, -R6 -N(R5 )C(=NR5 )N(R4 )R5, _R6 -N(R5 )c(=nr5 N(R4)CN, _R6-N(R5)C[=NC(9)OR4]_&gt;C R7 -N(R4)R5 &gt; -R6 -N=C(OR4 )R5 ^ -R6 -N=C(R4 )R^ &gt; .r6 . N=C(R4)R5, -R6-N(R5)-R6-OR5, -R6-S(0)pR4 and -R6_s(〇)tN(R4)R5, wherein each p-system is independently 0, 1 or 2, and each t is independently 丨 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, 128409 -19-200836743, hydroxyalkyl, alkoxy Alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally a substituted heterocyclylalkyl group, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R together with R5 and the nitrogen to which they are attached, form an optionally substituted N- a heterocyclic group or an optionally substituted N-heteroaryl; 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 、&quot;二取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 1〇·如請求項9之化合物，其係為3_(5_胺基蓁_丨_基&gt;2_丁基喳唑 琳-4(3H)-酮。 U·如請求項3之化合物，其中： η為1 ; 0 為稠合苯基； R1為氫； R2為氫或烷基； R為雜芳基，視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、鹵基、鹵烷基、鹵烯基、鹵 炔基、視情況經取代之環烷基、視情況經取代之環烷 基烷基、視情況經取代之環烷基烯基、視情況經取代 128409 •20- 200836743 之環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 务快基、視情況經取代之雜環基、視情況經取代之雜 環基烷基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、_R6_N〇2、^6^r5、 -R6-0S(0)2R4、-R6-〇c(〇)R4、_R6-C(〇)R4、r6_c(〇)〇r4、 _R6 -C(0)N(R4 )R5、-R6 _N(R4 )r5、-R6 _N(R5 )c(〇)R4、 -R6-N(R5)C(0)0R4 . -R6-N(R^)C(0)N(R^)R5 . .R6.N(R5)s(〇)tR4 , -R6 -N[S(0)t R4 ]2 ^ -R6，N(R5 )C(=NR5 )N(R4 )R5 λ .r6 .n^R5 )C(=NR5). n(r4)cn ^ Λ -r6-n(r5)- R7-N(R4)R5 . -R6-N=C(OR4)R5 . .R6-N=C(R4)R5 . -R6.N(r5).R6. 〇R R S(〇)pR 及-R6-S(〇)tN(R4)R5，其中各 p 係獨立為 0, 1或2，且各t係獨立為1或2 ; \ 各R4與R5係獨立選自包括氫、院基、烯基、炔基'鹵烧基、 經烧基、燒氧烧基、視情況經取代之環院基、視情況 α取代之％燒基烧基、視情況經取代之芳基、視情況 經取代之芳烧基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 彬成視情況經取代 或R與R5和彼兩者所連接 Ν雜環基或視情況經取代之队雜芳基· 各&quot;直接鍵結、m絲代之錢或分枝狀次炫基 128409 -21 - 200836743 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 12.如請求項11之化合物，其係選自包括： 5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-2,3-二氫-1H-啕哚-1-羧酸第 三-丁酯； 5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-1Η-啕哚-1-羧酸第三-丁酯； 2-丁基-3-(2,3-二氫-1Η-啕哚 _5-基）喹唑啉-4(3Η)-酮； 2-丁基-3-(1Η-啕哚-5-基）喳唑啉-4(3Η)-酮； 2-丁基-3-(2-酮基-2,3-二氫-1，3-苯并崎唑-5-基）喳唑啉-4(3Η)-酮； 5-(2-丁基-4-酮基喹唑啉-3(4Η)-基）-1Η-蚓唑-1-羧酸第三-丁醋； 2-丁基-3·(2-硫酮基-2,3·二氫-1Η-苯并咪唑-5-基）喹唑啉-4(3Η)-酮； 2- 丁基-3-(1Η-吲唑-5-基）喳唑啉-4(3Η)-酮； 3- (1Η-苯并三唑-5-基）-2-丁基喹唑啉-4(3Η)-酮； 3-(6-胺基外b。定-3-基）-2-丁基峻ϋ坐14木-4(3H)-S同， 2- 丁基-3-外1：啶-4·基喳唑啉-4(3H)-酮； 3- (l，3-苯并二氧伍圜烯-5-基）-2-丁基喹唑啉-4(3H)-酮； 2-丁基-3-(6-甲氧基吡啶-3-基）喳唑啉-4(3H)-酮； 5-(2-丁基-4-酮基喹唑啉-3(4H)-基）-2,3-二氫-1H-㈤哚小羧酸第 三-丁酯； 2·丁基-3-(6-酮基-5,6-二氫吡啶-3-基）喹唑啉-4(3H)-酮；及 128409 -22- 200836743 2·丁基、3介羥基_1，2·二氫吡啶-4-基 &gt;奎唑啉·4(3Η)-酮。 13·如請求項u之化合物，其係選自包括： 2 丁基、3_(2-硫基-1H-苯并咪唑I基）ττ奎唾淋_4(3h)-酮； [5-(2-丁基_4_酮基喹唑啉_3(4H)_基）吡啶_2_基]胺基甲酸第三 丁酯；及 2-丁基-3-(1-氧化p比咬基）π奎唾琳_4(3H)_酮。 14·如請求項3之化合物，其中： η為1 ; Q 為稠合苯基； R1為氫； R2為氫或烷基； R3為雜環基，視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、鹵基、鹵烷基、鹵烯基、鹵 炔基、 基烷基 視情況經取代之環烷基、視情況經取代之環烷 、視情況經取代之環烷基烯基、視情況經取代 之環烧基块基、視情況經取代之芳基、視情況經取代 1芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔土才見f月況1取代之雜環基、才見，清況經取代之雜 環基烧基、視情況經取代之雜環基稀基、視情況經取 代之雜基块基、視情況經取代之雜若基、視情況經 取代之雜芳烧基、視情況經取代之雜芳基稀基、視情 況經取代之雜芳基块基、_r6_cn、_r6_n〇2、_r6_〇r5、 -R6-OS(0)2R4 . -r6-〇C(〇)r4 ^ .r6_C(〇)r4 ^ _r6 c(〇)〇r4 , 128409 -23- 200836743 -R6 -C(0)N(R4 )R5 、-R6-N(R4)R5 、_R6 -N(R5 )C(0)R4 、 -R6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)S(0)tR4、 -R6 -N[S(0)t R4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、-R6 _N(R5 )C(==NR5 &gt; N(R4 )CN 、 -R6 -N(R5 )C[-NC(0)0R4 ]-N(R4 &gt;C(0)0R4 、 -R6 -N(R5 )-R7 -N(R4 )R5 - -R6 -N=C(OR4 )R5 &gt; -N=C(R4 )R5 &gt; -R6_N(R5)-R6-〇R5、-R6_S(〇)pR4 及-R6_S(〇)tN(R4)R5，其中各 P係獨立為0, 1或2，且各t係獨立為丨或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之_ 堤按之虱一起，形成視情況經取代之 N-雜環基或視情況經取代之N•雜芳基，· =為直=結、視情況經取代之直鏈或分枝狀次院基 γ視h况、..工取代之直鏈或分枝狀次稀基 經取代之直鏈或分枝狀次块基鍵；1 R7為直鏈或分枝狀次烷基鏈、 鏈或分枝狀讀基鏈。枝狀次縣鏈或直 15.如請求項14之化合物，其係選自包括： 2-丁基-3_[l-(2-羥基_3_苯氧基 _4(3办酮； 丙基L風峨咬斗基Μ唾琳 Μΐ-Ι&gt;(苄氧基&gt;2•經丙 土]/、氳吡啶冰基卜孓丁基喹唑啉 128409 •24- 200836743 -4(3H)-酮； 3- [H2-羥基-3_苯氧基丙基）六氫吡啶冰基]喹唑啉_4(3H),; 4- (2-丁基-4-酮基喳唑啉_3(4H)-基）六氫吡啶小羧酸第三·丁 酯；及 2-丁基-3-六氫吡啶-4-基喹唑啉-ΑΡΗ)-酮。 16.如睛求項3之化合物，其中： η為1 ; Q. 為稠合本基， R1為氫； R2為氮或烧基； R為環烷基，視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、鹵基、_烷基、函烯基、鹵 炔基、視丨㈢况經取代之環烧基、視情況經取代之環燒 基烧基、視情況經取代之環烷基烯基、視情況經取代 之環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烧基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基快基、-R6 -CN、-R6 、_R6 -〇R5、 -R6-0C(0)R4 &gt; -R6-OS(0)2R4 &gt; -R6-C(0)R4 . -R6-C(0)0R4 &gt; -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、_R6 -N(R5 )C(0)R4、 128409 -25- 200836743 -R6-N(R5 )C(0)〇R4 &gt; -R6-N(R5 )C(0)N(R4 )R5 - -R6-N(R5 )S(0)t R4 &gt; -R6 -N[S(0)t R4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、-R6 -N(R5 )C(=NR5 )· N(R4 )CN 、 -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 、 -R6 -N(R5 )-R7 -N(R4 )R5 ^ -R6 -N=C(OR4 )R5 &gt; .r6 -N=C(R4 )R5 &gt; -R6-N(R5)-R6-〇R5、-R6-S(0)pR4 及·Κ64(0)ίΝ(κ4)κ5，其中各 P係獨立為0, 1或2，且各t係獨立為i或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、^烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次院基 鏈、視情況經取代之直鏈或分枝狀次稀基鍵或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次稀基鏈或直 鏈或分枝狀次炔基鏈。 17·如請求項16之化合物，其係選自包括： 3-(4_胺基環己基）_2_丁基喳唑啉_4(班),·，與 [吵丁基斗酮基峻唾琳-3(傅| )環己基]胺基甲酸第三-丁 酉旨。 18·如請求項3之化合物，其中： 128409 -26- 200836743 η為1 ; Q 〇為稠合苯基； R1為氫； R2為氫或烷基； 反為方烧基’視情況被一或多個取代基取代，取代基選自 包括烷基、烯基、炔基、！i基、i烷基、鹵烯基、鹵 炔基、視情況經取代之環烷基、視情況經取代之環烷 基烧基、視情況經取代之環烧基晞基、視情況經取代 之環烷基炔基、視情況經取代之芳基、視情況經取代 之芳烷基、視情況經取代之芳烯基、視情況經取代之 芳炔基、視情況經取代之雜環基、視情況經取代之雜 環基烧基、視情況經取代之雜環基烯基、視情況經取 代之雜環基炔基、視情況經取代之雜芳基、視情況經 取代之雜芳烷基、視情況經取代之雜芳基烯基、視情 況經取代之雜芳基炔基、_R6_CN、_R6_N〇2、-R6-〇R5、 -R6-0C(0)R4 ^ »R6-〇S(0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 ^ -r6-c(o)n(r4)r5 、-R6-N(R4)R5 、-r6-n(r5)c(o)r4 、 -R6-N(R5)C(0)〇R4 . -R6-N(R5)C(0)N(R4)R5 ^ -R6-N(R5)S(0)tR4 λ -R6 -N[S(0)t R4 ]2 . .r6 .N(R5 )C(=nR5 )N(R4 )R5 &gt; -R6 -N(R5 )C(=NR5 y N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5). R7-N(R4)R5、-R6-N=C(〇R4)R5、-R6-N=C(R4)R5、-R6-N(R5)-R6_ 〇115、-116-8(〇)13 114及此义〇)洲114)]^5，其中各1)係獨立為0, 1或2，且各t係獨立為1或2; 128409 -27- 200836743 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、i烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R與R和彼兩者所連接之氮一起，形成視情況經取代之 队雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鍵、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次稀基鏈或直 鏈或分枝狀次炔基鏈。 19·如請求項18之化合物，其中·· η為1 ; 0 為稠合苯基； R1為氫； R2為氫或烷基； R3為节基，視情況被一或多個取代基取代，取代基選自包 括烧基、：^基、炔基、_基、_烧基、_烯基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 垸基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代之 128409 -28- 200836743 芳烧基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基院基、視情況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烧基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基…、-R6_n〇2、_R6-OR5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 . -R6-C(0)R4 - -R6-C(0)0R4 --R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)0R4 ^ -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 &gt; -R6 -N[S(0)t R4 ]2、-R6 _N(R5 )c(=nr5 例r4 )r5、_r6 _n(r5 似=皿5)_ N(R4)CN 、-R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 、 -R6-N(R5&gt;R7-N(R4)R5、_R6_N=c(〇R4)R5、_R6_N=C(R4)R5、 -R6 -N(R5 )-R6 -〇R5、-R6 _s⑼p r4 及·r6 _s⑼$ n(r4 )r5，其中各 P係獨立為0, 1或2，且各t係獨立為i或2 ; 各R4與R5係獨立選自包括氫、燒基、稀基、块基、_院基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； ㈣與R5和彼兩者料接之氮—起，形疏情論取代之 N-雜環基或視情況經取代之队雜芳基； 各於為直接鍵結、視情況經取代之直鏈或分枝狀次院基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 128409 •29- 200836743 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次稀基鏈或直 鏈或分枝狀次快基鏈。 20. 如請求項19之化合物，其係選自包括： 3-(4-胺基苄基）-2-丁基喹唑啉-4(3H)-酮；與 2-丁基-3·(‘硝基苄基）喹唑啉-4(3H)·酮。 21. 如請求項3之化合物，其中： η為1 ; Q, ^^為稠合本基， R1為氫； R2為氫或烷基；且 R3為羥烷基。 22. 如請求項21之化合物，其係選自包括： 2- 丁基-3-(2,3-二羥基丙基）喹唑啉-4(3Η)-酮；與 3- (2,3-二羥基丙基）-2-甲基喳唑啉-4(3Η)·酮。 23. 如請求項3之化合物，其中： η為1 ; Q 為稠合苯基； R1為氫； R2為氫或烷基； R3 為-R7 -N(R4 )R5 或-R7 -N(R4 )C(0)0R4 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 128409 -30· 200836743 經烧基、燒氧烧基、視情況經取代之環烧基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基；且 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈視^况經取代之直鍵或分枝狀次烯基鍵或視情況 經取代之直鏈或分枝狀次炔基鏈。 24·如請求項23之化合物，其係選自包括： [3-(2-丁基-4-酮基p奎唑琳-3(4H)·基）丙基]胺基甲酸第三_丁酯； [2-(2-丁基-4-酮基喹唑啉-3(4H)-基）乙基]胺基甲酸第三_丁酯； 3-(2•胺基乙基）-2-丁基喳唑啉-4(3H)-酮； 3-(3-胺基丙基）_2·丁基喳唑啉-4(3H)-酮； 2-丁基-3-(2-六氫p比咬-1-基乙基 &gt;奎吐琳-4(3H)-g同； 2·丁基-3-(3-六氫p比唆-1-基丙基 &gt;奎唾淋-4(3H)-_ ;及 2·丁基-3-(3-四氫吡咯小基丙基）喳唑啉_4(3H)，。 25·如請求項3之化合物，其中： η為1 ; Q 〇為稠合苯基； R1為氫； R2為氫或烷基； 128409 -31 - 200836743 R3為雜環基烷基，視情況被一或多個取代基取代，取代基 選自包括烷基、烯基、炔基、_基、鹵烷基、_烯基、 齒炔基、視情況經取代之環烷基、視情況經取代之環 烷基烷基、視情況經取代之環烷基烯基、視情況經取 代之環烷基炔基、視情況經取代之芳基、視情況經取 代之芳烧基、視丨月況經取代之芳稀基、視情況經取代 之芳炔基、視情況經取代之雜環基、視情況經取代之 雜環基烷基、視情況經取代之雜環基烯基、視情況經 取代之雜環基炔基'視情況經取代之雜芳基、視情況 經取代之雜芳烷基、視情況經取代之雜芳基烯基、視 情況經取代之雜芳基炔基、_R6-CN、HN〇2、_r0_〇r5、 -R6-0C(0)R4 ^ -R6-0S(0)2R4 , ^R6-C(0)R4 ^ -R6-C(0)OR4 . -R6-C(0)N(R4 )R5、-R6-N(R4)R5、-R6_n(R5)c(〇)r4、 -R6-N(R5 )C(0)〇R4 &gt; -R6-N(R5 )C(0)N(R4 )R5 - -R6-N(R5 )S(0)t R4 &gt; -R -N[S(0)t R4 ]2、_N(R5 )c(=nr5 )n(r4 )r5、_r6 _n(r5 )c卜皿5)_ N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 . -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 . -R6-N=C(R4)R5 . -R6-N(R5&gt; R6_OR5、-R、S(〇)pR4 及 _R6-S(〇)tN(R4)R5，其中各p 係獨立 為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、由烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 128409 -32- 200836743 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N-雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烧基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 26·如請求項25之化合物，其係為2_丁基各[2_(1_甲基四氫吡咯 -2-基）乙基]喹唑啉_4(3H)-酮。 27·如請求項3之化合物，其中： η為1 ; Q 〇為稠合苯基； R1 為氫、鹵基、-R6 -Ν〇2 或 _r6 _n(r4 )r5 ; R2為烧基或芳基； R3為芳基，視情況被一或多個取代基取代，取代基選自包 括烧基、烯基、炔基、_基、齒烧基、齒稀基、齒块 基視^況經取代之環院基、視情況經取代之環烧基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烧基块基、視情況經取代之芳基、視情況經取代之 芳炫基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基烷基、視情況經取代之雜環基烯基、視情況經取代 128409 -33 - 200836743 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、、_R6-〇H5、 -R6-0C(0)R4、-R6_OS(〇)2R4、-R6-C(〇)R4、r6_c(〇)〇r4、 -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6_N(R5)S(0)tR4、 -R -N[S(0)tR4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、_r6 _n(r5 )c(=NR5)_ N(R4 )CN 、 _R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 、 _R6-N(R5)-R7_N(R4)R5、-R6-N=&lt;：(OR4)R5、_r6_n=c(R4)r5、 -R6-N(R5)_R6-0r5、，其中各 P係獨立為0, 1或2，且各t係獨立為1或2 ; 各圮與R5係獨立選自包括氫、烷基、烯基、炔基、^烷基、 踁烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5*彼兩者所連接之氮—起，形成n兄經取代之 队雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分技狀次婦基鍵或視情況 、經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次焊基鍵或直 鏈或分枝狀次炔基鏈。 128409 -34- 200836743 28·如請求項27之化合物，其中： η為1 ; Q、. 為稠合苯基； Rl 為氫、鹵基、_RLN〇24-R6_n(r4)r5 ; R2為烷基或芳基； R為苯基’視情況被一或多個取代基取代，取代基選自包 括烧基、細基、快基 '鹵基、_烧基、鹵稀基、鹵炔 基、視情況經取代之環烷基、視情況經取代之環烷基 烧基、視情況經取代之環烷基烯基、視情況經取代之 環烧基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 块基、視情況經取代之雜環基、視情況經取代之雜環 基烧基、視情況經取代之雜環基烯基、視情況經取代 之雜環基快基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、-R6-CN、-R6-N02、-R6-OR5、 -R6-0C(0)R4、-R6-〇S(0)2R4、-R6-C(0)R4、-R6-C(0)0R4、 -R6-C(0)N(R4)R5 、 -R6-N(R4)R5 、 -R6-N(R5 )C(0)R4 、 -R6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)S(0)tR4、 _R6 -N[S(0)t R4 ]2、-R6 -N(R5 )C(=NR5 )N(R4 )R5、-R6 -N(R5 )C(=NR5 &gt; N(R4 )CN 、 -R6 -N(R5 )C[=NC(0)OR4 ]-N(R4 )-C(0)0R4 、 «R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 &gt; -R6-N(R5)_R6-0R5、-R6-S(0)pR4 及-R6-S(0)tN(R4)R5，其中各 -35- 128409 200836743 ^係獨立為〇, 1或2，且各t係獨立為1或2 ; 各R4與R5係、獨立選自包括氫、院基、烯基、炔基、鹵烧基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 I取代之環烷基烷基、視情況經取代之芳基、視情況 ^取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 29·如請求項28之化合物，其係選自包括： 3-(4-胺基苯基）-2-丁基-6-氣基喳唑啉_4(3H)_酮； 3-(4-胺基苯基）-2-丁基-7-氯基喳唑啉-4(3H)-酮； 2-丁基-7-石肖基-3-苯基峻峻琳-4(3H)-酮； 2- 丁基-6_硝基-3-苯基喳唑啉-4(3H)-酮； 7-胺基-2-丁基-3-苯基喹唑啉-4(3H)-酮； 6-胺基-2-丁基-3-苯基p奎。坐?林-4(3H)-S同， 3- (4-嗎福啉-4-基苯基）-2-{3-[3-(三氟甲基）苯氧基]苯基}喹唾 啉·4(3Η)_酮；及 3-(4-嗎福啉-4-基苯基）-2-苯基喳唑啉-4(3Η)-酮。 128409 -36 - 200836743 3〇·如請求項1之化合物，其中·· η為1至4 ; Q 〇為稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、鹵基、鹵烷 基、幽烯基、炔基、環烷基、環烷基烷基、環烷基 烯基'環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烧基、雜芳基烯基、雜芳基炔基、-R6 -CN、 ^R6-N02 &gt; -R6-〇R5 &gt; -R6-N(R4)R5 - -R6-S(0)pR4 &gt; -R6-C(0)R4 λ HC(S)R4、-R6-C(R4)2C(0)R5、-R6-C(0)0R4、-R6-〇C(〇)r4、 -R6-C(S)OR4、-R6-C(0)N(R4)r5、_R6_C⑸n(r4)r5、 -R6-n(r5)c(0)r4、-R6-N(R5)C(S)R4、-R6-N(R5)C(0)0R4、 -R6-n(r5)c(s)or4、-r6-n(r5)c(0)n(r4)r5、-R6-N(R5)c(s&gt; N(R4 )R5、-R6 -N(R5 )S(0)t R4、-R6 -N(R5 )S(0)t N(R4 妒、 -R6 -S(0)tN(R4 )R5、-R6 _n(R5 )C(=NR5 )N(R4 )R5 及-R6 _N(R5 似知 C(R4 )R5 )N(R4 )R5，其中各p係獨立為〇，1或2，且各t係獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烧基、晞基、炔基、鹵烧基、鹵烯基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基稀基、 128409 -37- 200836743 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氳、烷基、烯基、炔基、鹵烷基、齒烯基、鹵炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基…R6_N(R4)R5或 -R6-N(R4)C(〇)〇R4 ； 其中壞烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 鹵基_燒基、鹵烯基、ii炔基、視情況經取代之 環烧基、視情況經取代之環烧基烧基、視情況經取 代之環烧基烯基、視情況經取代之環燒基炔基、視 f月况經取代之芳基、視情況經取代之芳烧基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情驗取代之雜環基院基、 視情況經取代之雜環基烯基、視情驗取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烧基、視情況經取代之雜芳基稀基、視情況經 取代之雜芳基快基、-R6-CN、_R6_N〇2、h〇r5、 -R^0C(0)R4 &gt; ^.〇s(〇)2R4 . .r6^C(〇)r4 ^ ^r6-C(〇)〇r4 ^ 128409 -38- 200836743 -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、_R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)0R4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)_ S(0)tR4、-R6_N[S(0)tR4]2、-R6_n(R5)C(=NR5)N(R4)R5、 -R6-N(R5)C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4&gt; C(0)0R4、_r6 _n(R5 )_r7 _n(R4 )R5、-r6 _n=C(OR4 )R5、 -R6-N=C(R4)R5、-R6-N(R5&gt;R6_〇r5、-R6-S(〇)pR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次燒基 鏈、視情況經取代之直鏈或分枝狀次稀基鏈或視2 經取代之直鏈或分枝狀次炔基鏈；且 / R7為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次烯基鍵或直 鏈或分枝狀次炔基鏈。 31·如請求項30之化合物，其中·· η為1 ; 128409 -39- 200836743 Q 〇為稠合雜芳基； R1為氫或烷基； R2為氫或烷基； R3為芳基，視情況被一或多個取代基取代，取代基選自包 括烷基、烯基、炔基、函基、鹵烷基、鹵烯基、鹵炔 基、視h况經取代之環烧基、視情況經取代之環烷基 烷基、視情況經取代之環烷基烯基、視情況經取代之 環烷基炔基、視情況經取代之芳基、視情況經取代之 芳烷基、視情況經取代之芳烯基、視情況經取代之芳 炔基、視情況經取代之雜環基、視情況經取代之雜環 基烧基視^況經取代之雜環基烯基、視情況經取代 之雜環基炔基、視情況經取代之雜芳基、視情況經取 代之雜芳烷基、視情況經取代之雜芳基烯基、視情況 經取代之雜芳基炔基、_RLCN、_r6_n〇2、_r6_〇r5、 'R6-0C(0)R4 &gt; -R6-〇S(〇)2r4 . .R6-C(0)R4 &gt; -R6-C(0)〇R4 &gt; •R -C(〇)N(R4)R5、_R6_N(R4)R5、_r6_n(r5)c(〇)r4、 'R6«N(R5)C(0)0R4 . -R^N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 &gt; 'R -N[S(0)t R4 ]2 . .r6 _N(R5 )C(=NR5 )N(R4 )R5 - -R6 -N(R5 )C(=NR5 )-N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5)-R -N(R4)R5 . -R6-N=C(OR4)R5 . -R6.n=C(R4)R5 ^ -R6-N(R5)- R -〇R5、-R6_S(0)pR4 及-R6-S(0)tN(R4)R5，其中各 p 係獨立 為〇, 1或2，且各t係獨立為1或2 ; R與R係獨立選自包括氫、烷基、烯基、炔基、函烷基、 128409 200836743 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次快基鏈。 32. 如請求項31之化合物，其中： η為1 ; Q、…. 為祠合雜方基， R1為氫或烧基； R2為氫或烧基； R3為苯基，視情況被一或多個取代基取代，取代基選自包 括-R6-CN ' -R6_n〇2、-r6-n(r5)c(o)〇r4 及-R6-N(R4)R5 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、齒烷基、 魏烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 128409 -41 - 200836743 取代之雜環基燒基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與1^和彼兩者所連接之氮一起，形成視情況經取代之 队雜環基或視情況經取代之N-雜芳基；且 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次燒基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈。 33. 如請求項32之化合物，其係選自包括： 3-(4-胺基苯基）_2_丁基吡啶并[2&gt;d]嘧啶_4(3H)_酮； 3-(4-胺基苯基）_2_丁基喋啶_4(3H)·酮； 3-(4-胺基苯基）-2-丁基嘧吩并[2,3-d]嘧啶-4(3H)-酮； 3-(4-胺基苯基）_2_丁基嘧吩并[3,2_d]嘧啶-4(3H)-酮；及 3-(4-胺基苯基）-2-丁基-7-甲基ττ塞吩并[3,2-d]嘴咬-4(3H)-酮。 34. 如請求項32之化合物，其係選自包括： [4-(2-丁基斗酮基吡啶[2,3-d]嘧啶-3(411)_基）苯基]胺基甲酸第 三-丁酯； [4-(2-丁基斗酮基喋啶-3(4H)-基）苯基]胺基甲酸第三·丁酯；及 3-(4-胺基苯基）-2-丁基吡啶并[3,4-d]嘧啶-4(3H)-酮。 35. —種醫藥組合物，其包含藥學上可接受之賦形劑與式（乃 化合物： ΟEach R6 is a direct bond, optionally substituted straight or branched subalkyl chain, optionally substituted straight or branched subalkenyl chain or, as appropriate, &quot;disubstituted straight chain or a branched hypoalkynyl chain; and R7 is a linear or branched alkylene chain, a linear or branched secondary alkenyl chain or a linear or branched cisynyl chain. The compound of claim 9, which is a 3-(5-amino hydrazine-hydrazinyl group) 2- butyl oxazolidine-4(3H)-one. U. The compound of claim 3, Wherein: η is 1; 0 is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or an alkyl group; R is a heteroaryl group, optionally substituted by one or more substituents selected from the group consisting of alkyl groups and alkenes Alkyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl , if appropriate, replace the cycloalkylalkynyl group of 128409 •20-200836743, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, as appropriate Substituent, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted Aryl, optionally substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, _R6_N〇2, ^6 ^r5, -R6-0S(0)2R4, -R6-〇c(〇)R4, _R6-C(〇)R4, r6_c(〇)〇r4, _R6 -C(0)N(R4)R5,- R6 _N(R4 )r5, -R6 _N(R5 )c(〇)R4, -R6-N(R5)C(0)0R4 . -R6-N(R^)C(0)N(R^)R5 .R6.N(R5)s(〇)tR4 , -R6 -N[S(0)t R4 ]2 ^ -R6,N(R5 )C(=NR5 )N(R4 )R5 λ .r6 .n ^R5 )C(=NR5). n(r4)cn ^ Λ -r6-n(r5)- R7-N(R4)R5 . -R6-N=C(OR4)R5 . .R6-N=C( R4)R5 . -R6.N(r5).R6. 〇RRS(〇)pR and -R6-S(〇)tN(R4)R5, wherein each p is independently 0, 1 or 2, and each t system Independently 1 or 2; \ Each R4 and R5 are independently selected from the group consisting of hydrogen, affiliation, alkenyl, alkynyl, haloalkyl, pyrenyl, oxyalkyl, optionally substituted ring, and The α-substituted aryl group, optionally substituted aryl group, optionally substituted aryl group, optionally substituted heterocyclic group, optionally substituted heterocyclic group, optionally Substituted heteroaryl and optionally substituted heteroarylalkyl; substituted as appropriate or R and R5 and both attached to the heterocyclic group or optionally substituted heteroaryl group · each &quot; Direct bond, m-wired money or Dendritic shovel 128409 -21 - 200836743 Chain, optionally substituted linear or branched subalkenyl chain or optionally substituted linear or branched subalkynyl chain; and R7 is straight chain or A branched alkylene chain, a linear or branched secondary alkenyl chain or a linear or branched hypoalkynyl chain. 12. A compound according to claim 11 which is selected from the group consisting of: 5-(2-butyl-4-ketoquinazolin-3(4H)-yl)-2,3-dihydro-1H-indole 1-carboxylic acid tert-butyl ester; 5-(2-butyl-4-ketoquinazolin-3(4H)-yl)-1Η-indole-1-carboxylic acid tert-butyl ester; 2-butyl-3-(2,3-dihydro-1Η-啕哚_5-yl)quinazolin-4(3Η)-one; 2-butyl-3-(1Η-啕哚-5- Oxazoline-4(3Η)-one; 2-butyl-3-(2-keto-2,3-dihydro-1,3-benzoxazol-5-yl)oxazoline- 4(3Η)-keto; 5-(2-butyl-4-ketoquinazolin-3(4Η)-yl)-1Η-indazole-1-carboxylic acid tert-butyl vinegar; 2-butyl -3·(2-thioketo-2,3·dihydro-1Η-benzimidazol-5-yl)quinazoline-4(3Η)-one; 2-butyl-3-(1Η-carbazole -5-yl)oxazoline-4(3Η)-one; 3-(1Η-benzotriazol-5-yl)-2-butylquinazoline-4(3Η)-one; 3-(6 -amino-based b. 1,4--3-yl)-2-butyl ϋ ϋ 14 14 14 -4 (3H)-S, 2-butyl-3-exo 1: pyridin-4-yloxazoline-4 ( 3H)-keto; 3-(l,3-benzodioxanthene-5-yl)-2-butylquinazolin-4(3H)-one; 2-butyl-3-(6- Methoxypyridin-3-yl)oxazoline-4(3H)-one; 5-(2-butyl-4-ketoquinequine -3 - butyl 3-(4H)-yl)-2,3-dihydro-1H-(penta) hydrazinecarboxylic acid -3-yl)quinazoline-4(3H)-one; and 128409 -22-200836743 2·butyl, 3-hydroxyl_1,2·dihydropyridin-4-yl> quinazoline·4 3Η)-ketone. 13. The compound of claim u, which is selected from the group consisting of: 2 butyl, 3-(2-thio-1H-benzimidazole I group) ττ 奎 淋 _4(3h)-one; [5-( 2-butyl-4-ylketoquinazoline-3(4H)-yl)pyridine-2-yl]carbamic acid tert-butyl ester; and 2-butyl-3-(1-oxidized p-bite ) π 奎 琳 琳 _ 4 (3H) ketone. 14. The compound of claim 3, wherein: η is 1; Q is a fused phenyl; R1 is hydrogen; R2 is hydrogen or alkyl; R3 is heterocyclyl, optionally substituted by one or more substituents, The substituent is selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkynyl, alkyl optionally substituted cycloalkyl, optionally substituted cycloalkane, A substituted cycloalkylalkenyl group, optionally substituted cycloalkyl group, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aralkenyl, optionally Substituted alkyne soils can be seen in the substituted heterocyclic group, in the case of a heterocyclic group substituted, optionally substituted heterocyclic group, optionally substituted heteroblock a heteroaryl group, a heteroaryl group substituted as appropriate, a heteroaryl group substituted as appropriate, a heteroaryl block optionally substituted, _r6_cn, _r6_n〇2, _r6 _〇r5, -R6-OS(0)2R4 . -r6-〇C(〇)r4 ^ .r6_C(〇)r4 ^ _r6 c(〇)〇r4 , 128409 -23- 200836743 -R6 -C(0) N(R4)R5 -R6-N(R4)R5, _R6 -N(R5)C(0)R4, -R6-N(R5)C(0)0R4, -R6-N(R5)C(0)N(R4)R5 , -R6-N(R5)S(0)tR4, -R6 -N[S(0)t R4 ]2, -R6 -N(R5 )C(=NR5 )N(R4 )R5, -R6 _N( R5)C(==NR5 &gt; N(R4 )CN , -R6 -N(R5 )C[-NC(0)0R4 ]-N(R4 &gt;C(0)0R4 , -R6 -N(R5 ) -R7 -N(R4)R5 - -R6 -N=C(OR4)R5 &gt; -N=C(R4)R5 &gt; -R6_N(R5)-R6-〇R5, -R6_S(〇)pR4 and - R6_S(〇)tN(R4)R5, wherein each P is independently 0, 1 or 2, and each t is independently 丨 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, and alkyne. Alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl a heterocyclic group, optionally substituted heterocyclic alkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 and R5 and both _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Or a branch-like sub-hospital gamma-like condition, a linear or branched sub-block bond substituted by a linear or branched sub-dense substituted by a work; 1 R7 is a linear or branched An alkyl chain, a chain or a branched readyl chain. Branched sub-sector chain or straight 15. The compound of claim 14, which is selected from the group consisting of: 2-butyl-3_[l-(2-hydroxy-3-hydroxyl_4 (3 ketone; propyl) L wind 峨 Μ Μ Μ Μ Μ Ι Ι Ι Ι Ι Ι ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ; 3- [H2-hydroxy-3-phenoxypropyl) hexahydropyridine aryl] quinazoline _4 (3H), 4- (2-butyl-4-ketooxazoline _3 ( 4H)-yl)hexahydropyridine small carboxylic acid tert-butyl ester; and 2-butyl-3-hexahydropyridin-4-ylquinazoline-indole)-one. Wherein: η is 1; Q. is a fused radical, R1 is hydrogen; R2 is nitrogen or alkyl; R is cycloalkyl, optionally substituted by one or more substituents selected from alkyl groups including alkyl , alkenyl, alkynyl, halo, _alkyl, alkenyl, haloalkyn, fluorene (III) substituted cycloalkyl, optionally substituted cycloalkyl, optionally substituted ring Alkyl alkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aryl, optionally substituted Alkenyl, optionally substituted alkynyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heterocyclyl, optionally substituted Cycloalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryl fast radical, -R6-CN , -R6, _R6 - 〇R5, -R6-0C(0)R4 &gt; -R6-OS(0)2R4 &gt; -R6-C(0)R4 . -R6-C(0)0R4 &gt; -R6 -C(0)N(R4)R5, -R6 -N(R4)R5, _R6 -N(R5)C(0)R4, 128409 -25- 200836743 -R6-N(R5)C(0)〇R4 &gt; -R6-N(R5)C(0)N(R4)R5 - -R6-N(R5)S(0)t R4 &gt; -R6 -N[S(0)t R4 ]2, -R6 -N(R5 )C(=NR5 )N(R4 )R5, -R6 -N(R5 )C(=NR5 )· N(R4 )CN , -R6 -N(R5 )C[=NC(0)0R4 ]-N(R4)-C(0)0R4, -R6-N(R5)-R7-N(R4)R5^-R6-N=C(OR4)R5 &gt; .r6 -N=C(R4 ) R5 &gt; -R6-N(R5)-R6-〇R5, -R6-S(0)pR4 and ·Κ64(0)ίΝ(κ4)κ5, wherein each P line is independently 0, 1 or 2, and each t is independently i or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkyl Hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted a heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached Optionally substituted N-heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct-bonded, optionally substituted, linear or branched sub-base chain, optionally substituted a linear or branched subalkyne chain, or a linear or branched subalkenyl chain, optionally substituted; and R7 is a linear or branched sub-alkyl chain, a linear or branched sub-dense chain Or a linear or branched subalkynyl chain. 17. The compound of claim 16, which is selected from the group consisting of: 3-(4-aminocyclohexyl)_2-butyloxazoline _4 (ban), ·, and [noise butyl ketone base Lin-3 (Fu | ) cyclohexyl] carbamic acid third - butyl. 18. The compound of claim 3, wherein: 128409 -26-200836743 η is 1; Q 〇 is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or alkyl; and the opposite is a square alkyl group as the case may be Substituted by a plurality of substituents selected from the group consisting of alkyl, alkenyl, alkynyl groups, ! I-, i-alkyl, haloalkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylthiol, optionally substituted Cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclic , optionally substituted heterocyclic alkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroaryl Alkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, _R6_N〇2, -R6-〇R5, -R6-0C(0)R4^»R6-〇 S(0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 ^ -r6-c(o)n(r4)r5 , -R6-N(R4)R5 , -r6- n(r5)c(o)r4, -R6-N(R5)C(0)〇R4 . -R6-N(R5)C(0)N(R4)R5 ^ -R6-N(R5)S( 0) tR4 λ -R6 -N[S(0)t R4 ]2 . .r6 .N(R5 )C(=nR5 )N(R4 )R5 &gt; -R6 -N(R5 )C(=NR5 y N (R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5). R7-N(R4)R5,- R6-N=C(〇 R4) R5, -R6-N=C(R4)R5, -R6-N(R5)-R6_〇115, -116-8(〇)13 114 and this meaning)) 114)]^5, each of which 1) independently 0, 1 or 2, and each t is independently 1 or 2; 128409 -27- 200836743 each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, i-alkyl, Hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted a heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R together with R and the nitrogen to which they are attached Substituted heterocyclic groups or optionally substituted heteroaryl groups; each R6 is a direct-bonded, optionally substituted linear or branched alkylene bond, optionally substituted straight chain Or a branched sub-alkenyl chain or an optionally substituted linear or branched subalkynyl chain; and R is a linear or branched secondary alkyl chain, a linear or branched sub-dense chain or A linear or branched subalkynyl chain. 19. The compound of claim 18, wherein η is 1; 0 is a fused phenyl group; R1 is hydrogen; R2 is hydrogen or alkyl; R3 is a benzyl group, optionally substituted by one or more substituents, The substituent is selected from the group consisting of an alkyl group, a group, an alkynyl group, a hydrazino group, a hydrazino group, an alkenyl group, a haloalkynyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkyl fluorenyl group, Optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted 128409 -28-200836743 arylalkyl, optionally substituted Alkenyl, optionally substituted aralkynyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclic Alkynyl, optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6_n〇2 , _R6-OR5, -R6-0C(0)R4 &gt; -R6-0S(0)2R4 . -R6-C(0)R4 - -R6-C(0)0R4 -R6 -C(0)N (R4)R5, -R6 -N(R4)R5, -R6 -N(R5)C (0) R4, -R6-N(R5)C(0)0R4^-R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)S(0)tR4 &gt; -R6 -N[S(0)t R4 ]2, -R6 _N(R5 )c(=nr5 case r4 )r5, _r6 _n(r5 like=dish 5)_ N(R4)CN , -R6 -N( R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 , -R6-N(R5&gt;R7-N(R4)R5,_R6_N=c(〇R4)R5,_R6_N=C (R4) R5, -R6 - N(R5)-R6 - 〇R5, -R6 _s(9)p r4 and ·r6 _s(9)$ n(r4 )r5, wherein each P system is independently 0, 1 or 2, and each t is independent Is i or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, dilute, block, _, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally Substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl, optionally substituted a heteroaryl group and optionally a substituted heteroarylalkyl group; (d) a nitrogen heterocyclic group which is substituted with R5 and the two, and a N-heterocyclic group or a substituted heteroaryl group which is optionally substituted; Each of which is a linear or branched sub-base chain that is directly bonded, optionally substituted, and optionally substituted Branched-like alkenyl chain or, as appropriate, 128409 • 29- 200836743 substituted linear or branched subalkynyl chain; and R7 is a linear or branched secondary alkyl chain, linear or branched A dilute chain or a linear or branched sub-fast chain. 20. The compound of claim 19, which is selected from the group consisting of: 3-(4-aminobenzyl)-2-butylquinazolin-4(3H)-one; and 2-butyl-3. 'Nitrobenzyl) quinazolin-4(3H).one. 21. The compound of claim 3, wherein: η is 1; Q, ^^ is a fused base, R1 is hydrogen; R2 is hydrogen or alkyl; and R3 is hydroxyalkyl. 22. The compound of claim 21, which is selected from the group consisting of: 2-butyl-3-(2,3-dihydroxypropyl)quinazolin-4(3Η)-one; and 3-(2,3 -Dihydroxypropyl)-2-methyloxazoline-4(3Η)·one. 23. The compound of claim 3, wherein: η is 1; Q is a fused phenyl; R1 is hydrogen; R2 is hydrogen or alkyl; and R3 is -R7-N(R4)R5 or -R7-N (R4 C(0)0R4; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, 128409 -30· 200836743, burned, calcined, optionally substituted Cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkane a heteroaryl group substituted as appropriate and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclyl group or, as the case may be Substituted N-heteroaryl; and each R6 is a direct bond or a substituted straight or branched subalkyl chain, as the case may be substituted by a direct bond or a branched subalkenyl bond or, as appropriate A substituted linear or branched quaternary alkynyl chain. 24. The compound of claim 23, which is selected from the group consisting of: [3-(2-butyl-4-keto-p-quinazoline-3(4H)-yl)propyl]aminocarboxylic acid third-butyl Ethyl ester; [2-(2-butyl-4-ketoquinazolin-3(4H)-yl)ethyl]carbamic acid tert-butyl ester; 3-(2•aminoethyl)-2 -butyloxazoline-4(3H)-one; 3-(3-aminopropyl)_2.butyloxazoline-4(3H)-one; 2-butyl-3-(2-hexa) Hydrogen p is more than bitten-1-ylethyl&gt;Kudolin-4(3H)-g; 2·butyl-3-(3-hexahydrop than 唆-1-ylpropyl) -4(3H)--; and 2·butyl-3-(3-tetrahydropyrrolidinyl)oxazoline-4(3H), 25. The compound of claim 3, wherein: η is 1 ; Q 稠 is a fused phenyl group; R 1 is hydrogen; R 2 is hydrogen or alkyl; 128409 -31 - 200836743 R 3 is a heterocyclylalkyl group, optionally substituted by one or more substituents selected from the group consisting of Alkyl, alkenyl, alkynyl, yl, haloalkyl, alkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted ring Alkyl alkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl An aryl group substituted as appropriate, an aromatic group substituted as appropriate, an optionally substituted aralkynyl group, optionally substituted heterocyclic group, optionally substituted heterocyclic alkyl group, Optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl 'optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylene Base, optionally substituted heteroarylalkynyl, _R6-CN, HN〇2, _r0_〇r5, -R6-0C(0)R4^-R6-0S(0)2R4, ^R6-C(0 R4 ^ -R6-C(0)OR4 . -R6-C(0)N(R4 )R5, -R6-N(R4)R5, -R6_n(R5)c(〇)r4, -R6-N( R5)C(0)〇R4 &gt; -R6-N(R5)C(0)N(R4)R5 - -R6-N(R5)S(0)t R4 &gt; -R -N[S(0 )t R4 ]2, _N(R5 )c(=nr5 )n(r4 )r5, _r6 _n(r5 )c dish 5)_ N(R4)CN &gt; -R6-N(R5)C[=NC (0)0R4]-N(R4)-C(0)0R4 . -R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 . -R6-N= C(R4)R5 . -R6-N(R5&gt; R6_OR5, -R, S(〇)pR4 and _R6-S(〇)tN(R4)R5, wherein each p is independently 〇, 1 or 2, and Each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and alkane Alkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally Substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 and R5 and both The nitrogen to be bonded together forms an optionally substituted N-heterocyclic group or an optionally substituted N-heteroaryl group; each R6 is a direct-bonded, optionally substituted linear or branched sub-alkyl group. a linear or branched subalkenyl chain, or a linear or branched subalkynyl chain, optionally substituted, and optionally a straight or branched alkylene chain; Or a branched secondary alkenyl chain or a linear or branched subalkynyl chain. 26. The compound of claim 25 which is 2-butyl[2-(1-methyltetrahydropyrrolidin-2-yl)ethyl]quinazoline-4(3H)-one. 27. The compound of claim 3, wherein: η is 1; Q 〇 is a fused phenyl; R1 is hydrogen, halo, -R6-Ν〇2 or _r6 _n(r4)r5; R2 is alkyl or Aryl; R3 is an aryl group, optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, yl, dentate, dentate, and dentate Substituted ring, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally Substituted aromatic, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted Heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl group of 128409-33 - 200836743, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylene Base, optionally substituted heteroarylalkynyl, _R6-〇H5, -R6-0C(0)R4, -R6_OS(〇)2R4, -R6-C(〇)R4, r6_c(〇)〇r4 , -R6 -C (0)N(R4)R5, -R6-N(R4)R5, -R6-N(R5)C(0)R4, -R6-N(R5)C(0)0R4, -R6-N(R5 C(0)N(R4)R5, -R6_N(R5)S(0)tR4, -R -N[S(0)tR4 ]2, -R6 -N(R5 )C(=NR5 )N(R4 ) R5, _r6 _n(r5 )c(=NR5)_ N(R4 )CN , _R6 -N(R5 )C[=NC(0)0R4 ]-N(R4 )-C(0)0R4 , _R6-N (R5)-R7_N(R4)R5, -R6-N= &lt;:(OR4)R5, _r6_n=c(R4)r5, -R6-N(R5)_R6-0r5, wherein each P system is independently 0, 1 or 2, and each t system is independently 1 or 2; Each hydrazine and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkyl, decyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl. Alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted a heteroarylalkyl group substituted; or a nitrogen to which R4 and R5* are attached, forming a heterocyclic group substituted by n-branched or optionally substituted heteroaryl; each R6 is a direct bond a straight or branched sub-alkyl chain, optionally substituted linear or branched sub-base or optionally substituted linear or branched acetylene chain, as appropriate And R is a linear or branched sub-alkyl chain, a linear or branched sub-weld bond or a linear or branched subalkynyl chain. 128409 -34-200836743 28. The compound of claim 27, wherein: η is 1; Q, is a fused phenyl; R1 is hydrogen, halo, _RLN〇24-R6_n(r4)r5; R2 is alkyl Or aryl; R is phenyl' optionally substituted by one or more substituents selected from the group consisting of an alkyl group, a fine group, a fast group 'halo group, a ketone group, a halogen group, a haloalkyne group, Substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylenyl, optionally substituted aryl, optionally A substituted aralkyl group, optionally substituted aralkenyl group, optionally substituted aryl block group, optionally substituted heterocyclic group, optionally substituted heterocyclic group, optionally substituted Heterocyclylalkenyl, optionally substituted heterocyclyl, aryl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally Substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, -R6-0C(0)R4, -R6-〇S(0)2R4, -R6-C(0) R4, -R6-C(0)0R4, -R6- C(0)N(R4)R5, -R6-N(R4)R5, -R6-N(R5)C(0)R4, -R6-N(R5)C(0)0R4, -R6-N( R5)C(0)N(R4)R5, -R6-N(R5)S(0)tR4, _R6 -N[S(0)t R4 ]2, -R6 -N(R5 )C(=NR5 ) N(R4)R5, -R6 -N(R5)C(=NR5 &gt; N(R4 )CN , -R6 -N(R5 )C[=NC(0)OR4 ]-N(R4 )-C(0 ) 0R4 , «R6-N(R5)-R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 &gt; -R6-N(R5 ) _R6-0R5, -R6-S(0)pR4 and -R6-S(0)tN(R4)R5, wherein each -35-128409 200836743 ^ is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5, independently selected from the group consisting of hydrogen, deutero, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally Substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted Heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclyl or optionally substituted N-heteroaryl ; each R6 is a direct bond, as appropriate a substituted straight or branched alkylene chain, optionally substituted straight or branched subalkenyl chain or optionally substituted linear or branched nalkyne chain; and R7 is straight A chain or branched subalkyl chain, a linear or branched subalkenyl chain or a linear or branched hypoalkynyl chain. 29. The compound of claim 28, which is selected from the group consisting of: 3-(4-aminophenyl)-2-butyl-6-carbyloxazoline-4 (3H)-one; 3-(4 -aminophenyl)-2-butyl-7-chlorooxazoline-4(3H)-one; 2-butyl-7-succinyl-3-phenyl junjun-4(3H)-one ; 2-butyl-6-nitro-3-phenyloxazoline-4(3H)-one; 7-amino-2-butyl-3-phenylquinazoline-4(3H)-one 6-Amino-2-butyl-3-phenyl p-quinion. Sitting? Lin-4(3H)-S, 3-(4-morpholin-4-ylphenyl)-2-{3-[3-(trifluoromethyl)phenoxy]phenyl}quina Salinoline 4(3Η)-one; and 3-(4-morpholin-4-ylphenyl)-2-phenyloxazoline-4(3Η)-one. The compound of claim 1, wherein η is 1 to 4; Q 〇 is a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl , halo, haloalkyl, pentamyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl 'cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralyne , heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, -R6-CN, ^R6-N02 &gt; -R6-〇R5 &gt; -R6-N(R4)R5 - -R6-S(0)pR4 &gt; -R6-C(0)R4 λ HC(S)R4, -R6- C(R4)2C(0)R5, -R6-C(0)0R4, -R6-〇C(〇)r4, -R6-C(S)OR4, -R6-C(0)N(R4)r5 , _R6_C(5)n(r4)r5, -R6-n(r5)c(0)r4, -R6-N(R5)C(S)R4, -R6-N(R5)C(0)0R4, -R6-n (r5)c(s)or4, -r6-n(r5)c(0)n(r4)r5, -R6-N(R5)c(s&gt; N(R4)R5, -R6 -N(R5) S(0)t R4, -R6 -N(R5 )S(0)t N(R4 妒, -R6 -S(0)tN(R4 )R5, -R6 _n(R5 )C(=NR5 )N( R4) R5 and -R6 _N (R5 is analogous to C(R4)R5)N(R4)R5, wherein each p-system is independently 〇, 1 or 2, and each t-series is independently 1 or 2; or two phases The adjacent R1 groups together with the carbon or heterocyclic atom to which they are directly attached may form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl, and the remaining R1 groups, if present R2 is hydrogen, alkyl, decyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl Alkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclyl, 128409-37-200836743 heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylene Or a heteroarylalkynyl group; R3 is fluorene, alkyl, alkenyl, alkynyl, haloalkyl, alkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyl Alkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, Heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl...R6_N(R4)R5 or -R6-N(R4)C(〇)〇R4; wherein a bad alkyl group, a cycloalkylalkyl group, a cycloalkane Alkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aromatic A group, a heterocyclic group, a heterocyclylalkyl group, a heterocyclylalkenyl group, a heterocyclyl alkynyl group, a heteroaryl group, a heteroarylalkyl group, a heteroarylalkenyl group or a heteroaryl alkynyl group may be optionally one or more Substituted by a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, halo-alkyl, haloalkenyl, iialkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl An alkyl group, optionally substituted cycloalkylenyl group, optionally substituted cycloalkylenyl group, substituted aryl group, optionally substituted aryl group, optionally substituted Alkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl, heterocyclyl optionally substituted heterocyclyl, optionally substituted heterocycle Alkynyl, optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroaryl, optionally substituted heteroaryl, -R6-CN, _R6_N〇2, h〇r5, -R^0C(0)R4 &gt; ^.〇s(〇)2R4 . .r6^C(〇)r4 ^ ^r6-C(〇)〇r4 ^ 128409 -38- 200836743 -R6 -C(0)N(R4 )R5, -R6 -N (R4) R5, _R6 - N(R5)C(0)R4, -R6-N(R5)C(0)0R4, -R6-N(R5)C(0)N(R4)R5, -R6- N(R5)_ S(0)tR4, -R6_N[S(0)tR4]2, -R6_n(R5)C(=NR5)N(R4)R5, -R6-N(R5)C(=NR5) N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4&gt; C(0)0R4, _r6 _n(R5 )_r7 _n(R4 )R5, -r6 _n=C (OR4) R5, -R6-N=C(R4)R5, -R6-N(R5&gt;R6_〇r5, -R6-S(〇)pR4 and -R6-S(0)tN(R4)R5, Wherein each p is independently 〇, i or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, Alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclic Optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct-bonded, optionally substituted straight or branched secondary alkyl chain, as appropriate a substituted linear or branched sub-dense chain or a linear or branched subalkyne chain substituted with 2; and / R7 is a linear or branched sub-alkyl chain, straight chain or branched A secondary alkenyl bond or a linear or branched cis-alkynyl chain. 31. The compound of claim 30, wherein η is 1; 128409 - 39- 200836743 Q 〇 is a fused heteroaryl; R 1 is hydrogen or alkyl; R 2 is hydrogen or alkyl; R 3 is aryl, The case is substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, functional, haloalkyl, haloalkenyl, haloalkynyl, substituted cycloalkyl, visual a substituted cycloalkylalkyl group, optionally substituted cycloalkylalkenyl group, optionally substituted cycloalkylalkynyl group, optionally substituted aryl group, optionally substituted aralkyl group, optionally A substituted aralkenyl group, optionally substituted aralkynyl group, optionally substituted heterocyclic group, optionally substituted heterocyclic alkyl group, optionally substituted heterocyclylalkenyl group, optionally Substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _RLCN, _r6_n〇2, _r6_〇r5, 'R6-0C(0)R4 &gt; -R6-〇S(〇)2r4 . .R6-C(0)R4 &gt; -R6-C(0)〇R4 &gt; • R -C(〇)N( R4) R5, _R6_N(R4)R5, _r6_n(r5)c(〇)r4, 'R6«N(R5)C(0)0R4 . -R^N(R5)C(0)N(R4)R5 &gt ; -R6-N(R5)S(0)tR4 &gt; 'R -N[S(0)t R4 ]2 . .r6 _N(R5 )C(=NR5 )N(R4 )R5 - -R6 -N (R5)C(=NR5)-N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)-C(0)0R4 ^ -R6-N(R5 )-R -N(R4)R5 . -R6-N=C(OR4)R5 . -R6.n=C(R4)R5 ^ -R6-N(R5)- R -〇R5,-R6_S(0) pR4 and -R6-S(0)tN(R4)R5, wherein each p is independently 〇, 1 or 2, and each t is independently 1 or 2; R and R are independently selected from the group consisting of hydrogen and alkyl. Alkenyl, alkynyl, functional alkyl, 128409 200836743 hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, a substituted aralkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl group, optionally substituted heteroaryl group and optionally substituted heteroarylalkyl group; or R4 and R5, together with the nitrogen to which they are attached, forms an optionally substituted N-heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct bond, optionally substituted straight or branched shape a secondary alkyl chain, optionally substituted straight or branched subalkenyl chain or optionally substituted linear or branched nalynyl chain; and R7 is a linear or branched secondary alkyl chain a linear or branched subalkenyl chain or a linear or branched sub-fast chain. 32. The compound of claim 31, wherein: η is 1; Q, . . . is a heterocyclic group, R1 is hydrogen or alkyl; R2 is hydrogen or alkyl; R3 is phenyl, optionally taken by one or Substituted by a plurality of substituents selected from the group consisting of -R6-CN '-R6_n〇2, -r6-n(r5)c(o)〇r4 and -R6-N(R4)R5; each R4 is independent of R5 Selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, dentyl, weialkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally Substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, heterocyclyl substituted, optionally substituted heteroaryl, as appropriate, by 128409-41 - 200836743, and optionally Substituted heteroarylalkyl; or R4 together with the nitrogen to which 1^ and the two are attached, form an optionally substituted heterocyclyl or optionally substituted N-heteroaryl; and each R6 is straight Bonded, optionally substituted linear or branched sub-alkyl chain, optionally substituted linear or branched subalkenyl chain or optionally substituted linear or branched acetylene chain . 33. The compound of claim 32, which is selected from the group consisting of: 3-(4-aminophenyl)_2-butylpyrido[2&gt;d]pyrimidin-4(3H)-one; 3-(4- Aminophenyl)_2-butylacridine_4(3H)·one; 3-(4-aminophenyl)-2-butylsulfonyl[2,3-d]pyrimidine-4(3H) -ketone; 3-(4-aminophenyl)_2-butylsulfonyl[3,2-d]pyrimidin-4(3H)-one; and 3-(4-aminophenyl)-2-butyl -7-methyl ττ-seceno[3,2-d] mouth bite-4(3H)-one. 34. The compound of claim 32, which is selected from the group consisting of: [4-(2-butylindolylpyridine [2,3-d]pyrimidin-3(411)-yl)phenyl]aminocarbamic acid Tri-butyl ester; [4-(2-butyl keto) acridine-3(4H)-yl)phenyl]carbamic acid tert-butyl ester; and 3-(4-aminophenyl)- 2-butylpyrido[3,4-d]pyrimidin-4(3H)-one. 35. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a formula (ie compound: hydrazine) 其中： 128409 -42- 200836743 η為1至4 ; Q 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、鹵基、鹵烷 基、i烯基、i炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜$衣基、雜ί衣基烧基、雜ί哀基稀基、雜環基快基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R6 _CN、 -r6-no2 ^ -r6«〇r5 ^ -R6-N(R4)R5 ^ -R6-S(0)pR4 &gt; -R6-C(0)R4 . -R6-C(S)R4 &gt; -R6-C(R4)2C(0)R5 ^ -R6-C(0)OR^ ^ -R6.〇C(〇)R4 , -R6-C(S)OR4、_R6-C(0)N(R4)R5、_R6-C(S)N(R4 )R5、 -R6-n(r5)c(o)r4、-R6-N(R5)C(S)R4、-R6-N(R5)C(0)0R4、 _R6-N(R5)C(S)OR4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)C(扑 N(R4)R5 . -R6-N(R5)S(0)tR4 ^ -R6-N(R5)S(0)tN(R4)R5 , -R6 -S(0)tN(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及 _r6 _n(R5 )C(N== C(R4)R5)N(R4)R5，其中各p係獨立為〇, 1或2，且各t係獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子_ 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烧基、烯基、炔基、_烧基、鹵烯基、_炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳燒基、 务稀基、芳炔基、雜環基、雜環基烧基、雜環基稀基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基埽基或雜芳 128409 -43 - 200836743 基炔基； R為氫、烧基、烯基、炔基、_烧基、齒烯基、_炔基、 經烧基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、-R6_N(R4)R5或 -R6-N(R4)C(〇)〇R4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 鹵基、鹵烷基、i烯基、_炔基、視情況經取代之 環烷基、視情況經取代之環烷基烷基、視情況經取 代之裱烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烷基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜务基块基、-R6-CN、、-R^QR5、 -R6-0C(0)R4、_R6_〇s(〇)2r4、_r6 c(〇)r4、r6 _c⑼〇R4、 -R6-C(〇)N(R4)R5 . .r6.N(R4)R5 , .R6.N(R5)C(〇)R4 ^ 128409 -44- 200836743 -R6-N(R5 )C(〇)〇r4 . -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)-S(0)tR4 &gt; -R6.N[S(〇)tR4]2 . -R6-N(R5)C(=NR5)N(R4)R5 ^ -R6-N(R5)c(=NR5)N(R4)CN、-r6-n(r5)c[=nc(o)or4]-n(r4)- C(0)0R4、_R6 -N(R5 )_R7 -N(R4 )R5、-R6 -N=C(〇R4 )R5、 -R6-N==C(R4)R5、-R6_N(R5)-R6_OR5、-R6-S(0)PR4 及 •K^SCOXNCR4)!^，其中各p係獨立為〇，1或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 經烧基、燒氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮—起，形成視情況經取代之 N-雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情驗取代之直鏈或分枝狀次烧基 鏈視h况經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或料狀找基鏈'直鏈或分枝狀:㈣基鏈或直 鏈或分枝狀次炔基鏈； 為其立體異構物、對棠显捲&amp; 卞旱/、構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 36_ 一種式⑴化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上 J接文之鹽、溶劑合物或前體 128409 -45- 200836743 藥物於藥劑製造上之用途，該藥劑係在哺乳動物 預防或改善疾病或症狀，選自包括疼痛、抑鬱、 病、呼吸道疾病與精神病學疾病及其組合， 〇 中治療、 心血管疾Wherein: 128409 -42- 200836743 η is 1 to 4; Q is a fused aryl or fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkyl , i alkenyl, i alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heteromeric , hetero-heteroyl, heterocyclic, heteroaryl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, _R6-CN, -r6-no2^ -r6«〇r5 ^ -R6-N(R4)R5 ^ -R6-S(0)pR4 &gt; -R6-C(0)R4 . -R6-C(S)R4 &gt; -R6-C(R4 ) 2C(0)R5 ^ -R6-C(0)OR^ ^ -R6.〇C(〇)R4 , -R6-C(S)OR4, _R6-C(0)N(R4)R5, _R6- C(S)N(R4)R5, -R6-n(r5)c(o)r4, -R6-N(R5)C(S)R4, -R6-N(R5)C(0)0R4, _R6 -N(R5)C(S)OR4, -R6-N(R5)C(0)N(R4)R5, -R6-N(R5)C(FON(R4)R5 . -R6-N(R5 )S(0)tR4 ^ -R6-N(R5)S(0)tN(R4)R5 , -R6 -S(0)tN(R4 )R5, -R6 -N(R5 )C(=NR5 )N (R4) R5 and _r6 _n(R5)C(N== C(R4)R5)N(R4)R5, wherein each p-system is independently 〇, 1 or 2, and each t-series is independently 1 or 2; Or two adjacent R1 groups and their direct The carbon or heterocyclic atom may form a fused ring selected from a cycloalkyl group, an aryl group, a heterocyclic group or a heteroaryl group, and the remaining R1 groups, if present, are as described above; R2 is hydrogen, An alkyl group, an alkenyl group, an alkynyl group, a decyl group, a haloalkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkylalkenyl group, an aryl group, an arylalkyl group, a dilute group, an alkyne group Or a heterocyclic group, a heterocyclic alkyl group, a heterocyclic group, a heterocyclyl alkynyl group, a heteroaryl group, a heteroarylalkyl group, a heteroarylalkyl group or a heteroaryl group 128409-43 - 200836743; R is hydrogen, alkyl, alkenyl, alkynyl, decyl, alkenyl, ynkynyl, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl , aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroaryl Alkenyl, heteroarylalkynyl, -R6_N(R4)R5 or -R6-N(R4)C(〇)〇R4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkyl Alkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, A cycloalkenyl, a heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl groups, Alkenyl, alkynyl, halo, haloalkyl, i-alkenyl, ynkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted decylalkylene Substituted, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted alkynyl, optionally Substituted heterocyclic group, optionally substituted heterocyclylalkyl group, optionally substituted heterocyclylalkenyl group, optionally substituted heterocyclic alkynyl group, optionally substituted heteroaryl group, Substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted hydroxyl base, -R6-CN, -R^QR5, -R6-0C(0)R4 , _R6_〇s(〇)2r4, _r6 c(〇)r4, r6 _c(9)〇R4, -R6-C(〇)N(R4)R5 . .r6.N(R4)R5 , .R6.N(R5 )C(〇)R4 ^ 128409 -44- 200836743 -R6-N(R5 )C(〇) 〇r4 . -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)-S(0)tR4 &gt; -R6.N[S(〇)tR4]2 . R6-N(R5)C(=NR5)N(R4)R5 ^ -R6-N(R5)c(=NR5)N(R4)CN, -r6-n(r5)c[=nc(o)or4 ]-n(r4)- C(0)0R4, _R6 -N(R5)_R7 -N(R4)R5, -R6 -N=C(〇R4)R5, -R6-N==C(R4)R5 , -R6_N(R5)-R6_OR5, -R6-S(0)PR4 and •K^SCOXNCR4)!^, where each p-system is independently 〇, 1 or 2, and each t-series is independently 1 or 2; each R4 Independently selected from R5, includes hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl , optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally Substituted heteroarylalkyl; or R4 and R5 and the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or, optionally substituted, heteroaryl; each R6 is a direct bond Depending on the situation, the linear or branched sub-alkenyl chain may be substituted or replaced by a linear or branched sub-alkenyl chain. a linear or branched subalkyne chain substituted; and R7 is a straight chain or a material-like base chain 'straight or branched: (iv) a base chain or a linear or branched subalkynyl chain; a stereoisomer thereof, a guanidine roll &amp; a drought/structure, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 36_ A compound of the formula (1) as a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or precursor thereof 128409-45-200836743 The use of the agent for preventing or ameliorating a disease or symptom in a mammal, including pain, depression, disease, respiratory disease and psychiatric disease, and combinations thereof, treatment of sputum, cardiovascular disease 其中： η為1至4 ; GI 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烧基、稀基、炔基、_基、齒烧 基、齒烯基、函炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基…R6_CN、 -R6-N02 &gt; -R6-〇r5 , -R6.N(R4)R5 ^ -R6-S(0)pR4 ^ -R6-C(0)R4 ^ -R6-C(S)R4 &gt; -R6-C(R4 )2 C(0)R5 - -R6-C(0)0R4 &gt; -R6-〇C(0)R4 ^ -R6 -C(S)OR4 、-R6 -C(0)N(R4 )R5 、_R6 -C(S)N(R4 )R5 、 -R6-N(R5 )C(0)R4 . -R6-N(R5 )C(S)R4 &gt; -R6-N(R5 )C(0)OR4 &gt; -R6-N(R5)C(S)OR4 ^ -R6-N(R5)C(0)N(R4)R5 ^ -R6.N(R5)C(S&gt; N(R4 )R5、-R6 -N(R5 )S(0)t R4、-R6 -N(R5 )S(0)t N(R4 )R5、 -R6 -S(0)tN(R4 )R5 、 -R6 -N(R5 )C(=NR5 )N(R4 )R5 及 -R6-N(R5)C(N=C(R4)R5)N(R4)R5，其中各 p 係獨立為 〇, i 或 2，且各t係獨立為1或2 ; 128409 -46- 200836743 戒兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基’而其餘Rl基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烧基、環烷基烷基、環烷基烯基、芳基、芳烧基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； H3為氫 '烷基、烯基、炔基、_烷基、函烯基、_炔基、 經燒基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基 '雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、_R7啊R4)R5或 -R7-N(R4)C(0)0R4 ； 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 A基、_烧基、函烯基、！I炔基、視情況經取代之 環烧基、視情況經取代之環烷基烷基、視情況經取 代之環烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 l2S4〇9 -47- 200836743 況經取代之雜環基、視情況經取代之雜環基烷基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基'視情況經取代之雜芳基烯基、視情況經 取代之雜方基快基、-R6-CN、、 -R6-〇C(〇)R4、_R6_〇S(〇)2r4、-R6_c(〇)r4、R6_q〇)〇R4、 -R6-C(〇)N(R4)R5、_R6-N(R4)R5、-R6_n(r5)c(〇)r4、 -R6-N(R5)C(〇)〇R4、_R6-N(R5)C(〇)n(r4)r5、_r6_n(r5)_ S(〇X R4 &gt; .r6 -N[S(0)t R4 ]2 - -R6 -N(R5 )C(=NR5 )N(R4 )R5 --R6-N(R5 )C(=NR5 )N(R4 )CN &gt; -R6-N(R5)C[=NC(0)〇R4]-N(R4&gt; C(0)0R4、_R6，r5)_r7_n(r4)r5、r6_n=c(〇r”r5、 -R6.C(R4)R5、_R6_n(r5&gt;r6 视5、_R6 _s(〇)pR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各t 係獨立為1或2 ; 各R與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 、、二取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R舁R和彼兩者所連接之氮一起，形成視情況經取代之 π雜環基或視情況經取代之N_雜芳基； 各R為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鍵' 視情況經取代之直鏈或分枝狀次烯基鏈或視情況 128409 •48- 200836743 經取代之直鏈或分枝狀次炔基鏈；且 H鏈或分枝狀找基鏈、直鏈或純狀㈣基鍵或直 鏈或分枝狀次炔基鏈。 、扁X性疼痛、内臟疼痛、癌症疼痛、化學療法疼 卜傷疼痛、手術疼痛、手術後疼痛、生產疼痛、分娩 2、神經發生性膀胱、潰瘍性結腸炎、慢性疼痛、持續 性疼痛、末梢媒介之疼痛、中樞媒介之疼痛、慢性頭痛: 偏t痛、竇房結頭痛、緊張頭痛、幻想肢疼痛、末梢神經 損傷及其組合。 38.如請求項36之用途，其中該疾病或症狀係選自包括盘HIV 有關聯之疼痛、mv治療所引致之神經病、三又神經痛、 賴神經痛、正常疼痛、熱敏感性、局部肉狀瘤病、刺 激性腸徵制、克隆氏病、與多發性硬化_有關聯之疼 痛、肌委縮性側索硬化(ALS)、糖尿病患者之神經病、末 梢神經病、關節炎、風濕性關節炎、骨關節炎、動脈粥瘤 硬化、陣發性肌緊張不足、肌無力徵候襄、肌強直、惡性 U '膽囊纖維變性、㈣固綱過多症、橫紋肌溶解、甲 2腺機能減退症、兩極抑鬱、焦慮、精神分裂症、納通道 毒素相關疾病、家族性肢端紅痛病、原發性肢端紅痛病、 家族性直腸疼痛、癌症、癲癇、部份與-般緊張發作、不 安寧腳部徵候蔟、節律不齊、纖維肌痛、在因中風或神經 損傷所造成之絕血狀態下之神經保護、快速節律不齊、心 房纖維顫動及心室纖維顫動。 128409 -49- 200836743 39.-種式(1)化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 樂物在哺乳動物中治療疼痛之用途，其方式是在該痛乳動 物中抑制離子通量經過電壓依賴性鈉通道，Wherein: η is 1 to 4; GI is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, dilute, alkynyl, yl, dentate, alkenyl, Alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl ,heterocyclylalkenyl,heterocyclylalkynyl,heteroaryl,heteroarylalkyl,heteroarylalkenyl,heteroarylalkynyl...R6_CN, -R6-N02 &gt; -R6-〇r5 , -R6 .N(R4)R5 ^ -R6-S(0)pR4 ^ -R6-C(0)R4 ^ -R6-C(S)R4 &gt; -R6-C(R4 )2 C(0)R5 - - R6-C(0)0R4 &gt; -R6-〇C(0)R4 ^ -R6 -C(S)OR4 , -R6 -C(0)N(R4 )R5 , _R6 -C(S)N(R4 R5, -R6-N(R5)C(0)R4. -R6-N(R5)C(S)R4 &gt; -R6-N(R5)C(0)OR4 &gt; -R6-N(R5 C(S)OR4 ^ -R6-N(R5)C(0)N(R4)R5 ^ -R6.N(R5)C(S&gt; N(R4 )R5, -R6 -N(R5 )S( 0)t R4, -R6 -N(R5)S(0)t N(R4)R5, -R6 -S(0)tN(R4)R5, -R6 -N(R5)C(=NR5 )N( R4)R5 and -R6-N(R5)C(N=C(R4)R5)N(R4)R5, wherein each p is independently 〇, i or 2, and each t is independently 1 or 2; 128409 -46- 200836743 Ring two adjacent R1 The groups together with the carbon or heterocyclic atom to which they are directly attached may form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl and the remaining R1 groups, if present, are R2 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, arylalkyl, Aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl H3 is hydrogen 'alkyl, alkenyl, alkynyl, _alkyl, alkenyl, ynkynyl, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkyne Base, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl 'heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroaryl Alkenyl, heteroarylalkynyl, _R7, R4)R5 or -R7-N(R4)C(0)0R4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkyne Base, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, A cycloalkenyl, a heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl groups, Alkenyl, alkynyl, A-based, _alkyl, alkenyl, An alkynyl group, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted An aryl group, optionally substituted aralkyl group, optionally substituted aralkenyl group, optionally substituted aralkynyl group, optionally as described above, a heterocyclic group substituted, optionally, as appropriate Substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclylalkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl' Optionally substituted heteroarylalkenyl, optionally substituted heteroaryl radical, -R6-CN, -R6-〇C(〇)R4, _R6_〇S(〇)2r4, -R6_c( 〇)r4, R6_q〇)〇R4, -R6-C(〇)N(R4)R5, _R6-N(R4)R5, -R6_n(r5)c(〇)r4, -R6-N(R5)C (〇)〇R4, _R6-N(R5)C(〇)n(r4)r5, _r6_n(r5)_ S(〇X R4 &gt; .r6 -N[S(0)t R4 ]2 - -R6 -N(R5 )C(=NR5 )N(R4 )R5 --R6-N(R5 )C(=NR5 )N(R4 )CN &gt; -R6-N(R5)C[=NC(0)〇 R4]-N(R4&gt; C(0)0R4, _R6, r5)_r7_n(r4)r5, r6_n=c(〇r"r5, -R6.C(R4)R5, _R6_n(r5&gt;r6 视5, _R6 _s(〇)pR4 and -R6-S(0)tN(R4)R5, wherein each p-system is independently 〇, i or 2, and Each t is independently 1 or 2; each R and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl. And optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl Optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R舁R together with the nitrogen to which they are attached, form an optionally substituted π heterocyclyl or, as appropriate, substituted N_heteroaryl; each R is a direct bond, optionally substituted straight or branched subalkyl bond', or a linear or branched subalkenyl chain, as appropriate, or as appropriate 128409 •48 - 200836743 Substituted linear or branched subalkynyl chain; and H chain or branched base chain, linear or pure (tetra) base bond or linear or branched hypoalkynyl chain. Sexual pain, visceral pain , cancer pain, chemotherapy pain, surgical pain, postoperative pain, production pain, childbirth 2, neurogenic bladder, ulcerative colitis, chronic pain, persistent pain, pain in the distal media, pain in the central media Chronic headache: partial pain, sinus headache, nervous headache, fantasy limb pain, peripheral nerve injury and their combination. 38. The use of claim 36, wherein the disease or condition is selected from the group consisting of a pain associated with HIV, a neuropathy caused by mv therapy, a tri-neural pain, a neuralgia, a normal pain, a heat sensitivity, a local meat Sarcoidosis, irritative bowel syndrome, Crohn's disease, pain associated with multiple sclerosis, skeletal lateral sclerosis (ALS), neuropathy in diabetic patients, peripheral neuropathy, arthritis, rheumatoid arthritis, Osteoarthritis, atherosclerosis, paroxysmal muscle tone deficiency, muscle weakness syndrome, myotonia, malignant U ' gallbladder fibrosis, (4) hypertrophy, rhabdomyolysis, hypothyroidism, bipolar depression, Anxiety, schizophrenia, nanochannel toxin-related diseases, familial acromegaly, primary acromegaly, familial rectal pain, cancer, epilepsy, partial and general tension, restless feet Symptoms of sputum, irregular rhythm, fibromyalgia, neuroprotection due to stroke or nerve damage, rapid rhythm, atrial fibrillation, and ventricular fibrillation. 128409-49-200836743 39.- Compounds of formula (1) as their stereoisomers, palmomers, tautomers or mixtures thereof or pharmaceutically acceptable salts, solvates or precursors thereof The use of a substance to treat pain in a mammal by inhibiting ion flux through a voltage-dependent sodium channel in the lactating animal, 其中： η為1至4 ; Q 〇為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、函基、齒烷 基、i烯基、炔基、環烷基、環烷基烷基、環烷基 烯基、環烧基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基 '雜芳烷基、雜芳基烯基、雜芳基炔基…R6_CN、 -R6-N02、-R6-〇R5、-R6-N(R4)R5、-R6-S(0)pR4、-R6-CX〇)R4 ' -R6-C(S)R4、-R6-C(R4)2C(0)R5、妒-(：(0)0圮、_R6-〇c(〇)R4、 -R6 -C(S)OR4、-R6 -C(0)N(R4 )R5、# -C(S)N(R4 )r5、 &gt;R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(S)R4 &gt; .R6-N(R5)C(0)0R4 , -R6-N(R5)C(S)OR4、-R6-N(R5)C(0)N(R4)R5、-R6-N(R5)C(S&gt; N(R4)R5、_R6-N(R5)S(0)tR4、_R6-N(R5)S(0)tN(R4)R5、 -R6 -S(0)t N(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 _N(R5 )qN&gt; C(R4)R5)N(R4)R5，其中各p係獨立為0, 1或2，且各t係獨 128409 -50- 200836743 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R為氣、烧基、細基、快基、_烧基、_稀基、_快基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烧基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基块基； R3為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、_R7_N(R4)RS或 -R7-n(r4)c(o)or4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、Wherein: η is 1 to 4; Q 〇 is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, functional, chiral, i-alkenyl , alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylenyl, aryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl ,heterocyclylalkenyl,heterocyclylalkynyl,heteroaryl 'heteroarylalkyl,heteroarylalkenyl,heteroarylalkynyl...R6_CN, -R6-N02, -R6-〇R5, -R6- N(R4)R5, -R6-S(0)pR4, -R6-CX〇)R4 '-R6-C(S)R4, -R6-C(R4)2C(0)R5,妒-(:( 0)0圮, _R6-〇c(〇)R4, -R6 -C(S)OR4, -R6 -C(0)N(R4)R5, # -C(S)N(R4)r5, &gt; R6-N(R5)C(0)R4 &gt; -R6-N(R5)C(S)R4 &gt; .R6-N(R5)C(0)0R4 , -R6-N(R5)C(S )OR4, -R6-N(R5)C(0)N(R4)R5, -R6-N(R5)C(S&gt; N(R4)R5, _R6-N(R5)S(0)tR4, _R6 -N(R5)S(0)tN(R4)R5, -R6 -S(0)t N(R4)R5, -R6 -N(R5)C(=NR5 )N(R4 )R5 and -R6 _N (R5)qN&gt; C(R4)R5)N(R4)R5, wherein each p-system is independently 0, 1 or 2, and each t-system is 128409-50-200836743 is set to 1 or 2; or two adjacent R1 group and their The linked carbon or heterocyclic atom may form a fused ring selected from a cycloalkyl group, an aryl group, a heterocyclic group or a heteroaryl group, and the remaining R1 groups, if present, are as described above; R is a gas, Alkyl group, a fine group, a fast group, a ketone group, a benzyl group, a benzyl group, a cycloalkyl group, a cycloalkylalkyl group, a cycloalkylalkenyl group, an aryl group, an arylalkyl group, an aralkenyl group, an alkyne group , heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroaryl block; R3 is hydrogen, alkane Base, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aromatic Alkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroaryl Alkynyl, _R7_N(R4)RS or -R7-n(r4)c(o)or4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, 芳基、芳烧基、芳稀基、芳炔基、雜環基、雜環基 烧基、雜環基烯基、雜環基炔基、㈣基、雜芳烧 基、雜芳基烯基或雜芳基炔基可視情況被—或多個 烯基、炔基、 取代基取代，取代基選自包括烷基 代之環烷基烯基、 情況經取代之芳基 =基、鹵烧基、i烯基、4块基、視情況經取代之 環烷基、視情況經取代之環烷基烷基、視情況經取 視情況經取代之環烷基炔基、視 、視情況經取代之芳烷基、視情 200836743 況經取代之芳烯基、視情況經取代之芳炔美、視产 況經取代之雜環基、視情況經取代之雜環基烷其、 視情況經取代之雜環基稀基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、-R6_CN、-R6-N〇2、、 -R6-0C(0)R4、-R6-0S(0)2R4、_R6-C(〇)r4、r6 _c(〇)〇r4、 -R6-C(0)N(R4)R5、_r6_n(R4)R5、-r6_n(r5)c(〇)r4、 -r6-n(r5)c(o)or4、-R6_n(R5)c(〇)n(r4)r5、r6_n(r5&gt; S(0)tR4、-R6-N[S(0)tR4]2、_R6-N(R5)c(=NR5)N(R4)R5、 -R6-N(R5)C(=NR5)n(R4)cn、妒啊r5)c卜nc(〇)〇r4] n(r4)· C(0)0R4 ^ -R6-N(R5&gt;r7-N(R4)R5 . -R6.N=C(OR4)R5 , •R6-N=C(R4)R5、-R6-N(R5)-R6-〇r5、-R6-S(0)PR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 私院基、烧氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N-雜芳基； 各R為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 128409 -52- 200836743 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 40.—種式（I)化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 藥物在哺乳動物之細胞中降低離子通量經過電壓依賴性 鈉通道之用途，Aryl, arylalkyl, aryl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, (tetra)yl, heteroarylalkyl, heteroarylalkenyl Or a heteroarylalkynyl group may be optionally substituted by a plurality of alkenyl groups, alkynyl groups, substituents selected from cycloalkylalkyl groups including alkyl groups, substituted aryl groups, halogen groups, i Alkenyl, 4-block, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, substituted cycloalkylalkynyl as appropriate, optionally substituted Alkyl, as appropriate, 200836743 conditionally substituted aralkenyl, optionally substituted alkyne, substituted heterocyclyl, optionally substituted heterocycloalkane, optionally substituted A cycloalkyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted Heteroarylalkynyl, -R6_CN, -R6-N〇2, -R6-0C(0)R4, -R6-0S(0)2R4, _R6-C(〇)r4, r6 _c(〇)〇 R4, -R6-C (0) N(R4)R5, _r6_n(R4)R5, -r6_n(r5)c(〇)r4, -r6-n(r5)c(o)or4, -R6_n(R5)c(〇)n( R4)r5, r6_n(r5&gt; S(0)tR4, -R6-N[S(0)tR4]2, _R6-N(R5)c(=NR5)N(R4)R5, -R6-N(R5 C(=NR5)n(R4)cn, 妒 rr5)c nc(〇)〇r4] n(r4)· C(0)0R4 ^ -R6-N(R5&gt;r7-N(R4)R5 -R6.N=C(OR4)R5 , •R6-N=C(R4)R5, -R6-N(R5)-R6-〇r5, -R6-S(0)PR4 and -R6-S( 0) tN(R4)R5, wherein each p is independently 〇, i or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, Alkyl, phenyloxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, Optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 and R5 and both Together with the nitrogen, an optionally substituted N-heterocyclic group or an optionally substituted N-heteroaryl group; each R is a direct-bonded, optionally substituted linear or branched alkylene group 12840 9-52-200836743 Chain, optionally substituted straight or branched subalkenyl chain or optionally substituted linear or branched nalkenyl chain; and R7 is a linear or branched hypoalkane A base chain, a straight chain or a branched subalkenyl chain or a linear or branched quaternary alkynyl chain. 40. A compound of the formula (I) as a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof in a mammalian cell The use of a reduced voltage flux through a voltage-dependent sodium channel, 其中： η為1至4 ; Q 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、鹵基、鹵烷 基、齒烯基、齒炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R6 _CN、 -R6-N02、-R6_OR5、_R6 麵N(R4)R5、_R6_s(〇)pR4、_r6 _c(〇)r4、 -R6-C(S)R4、-R6-C(R4)2C(〇)R5、_R6-C(〇)〇r4、r6 〇c(〇)r4、 ~R6 O(S)OR4 、-R6 -C(0)N(R4 )R5 、-R6 -C(S)N(R4 )R5 、 -R6-N(R5)C(〇)R4、-R6-N(R5)C⑻R4、hn(r5)c(〇)〇r4、 128409 -53 - 200836743 -r6-n(r5)c(s)or4、-r6-n(r5)c(o)n(r4)r5、-rln(R5)c(s&gt; N(R4 )R5、-R6 _n(r5 )s(〇)t r4、_r6 _n(r5 )s(〇)t n(r4 )r5、 _R6 -S(0)t N(R4 )R5、_R6 -N(R5 )c(=nr5 )N(R4 )r5 及 _R6 _n(r5 )c(_ C(R4)R5)N(R4)R5，其中各p係獨立為〇, 1或2，且各t係獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基'雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烷基、烯基、炔基、齒烷基、鹵烯基'齒炔基、 經燒基、環烷基、環烷基烷基、環烷基烯基、環烷基 快基、芳基、芳烧基、芳烯基、芳快基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烧基、雜芳基烯基、雜芳基炔基、_R7-N(R4)R5或 _R7-n(r4)c(o)or4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 燒基、雜環基烯基、雜環基炔基、雜芳基、雜芳烷 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 128409 -54- 200836743 鹵基、i烷基、_烯基、鹵炔基、視情況經取代之 環烧基、視情況經取代之環烷基烷基、視情況經取 代之環烧基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烷基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、_R6_CN、_R6-N〇2、_r6_〇r5、 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 &gt; -R6-C(0)R4 &gt; -r6-c(〇)〇r4 &gt; -R6-C(0)N(R4)R5、-R6_N(R4)R5、_r6_n(r5)c(〇)r4、 -R6-N(R5)C(0)0R4 &gt; -R6-N(R5)C(0)N(R4)R5 . .Κ6.Ν(Κ5}. S(0)tR4、_R6-N[S(0)tR4]2、-r6_n(r5)c(；=nr5)n(r4)r5、 -R6.N(R5)C(=NR5)N(R^)CN &gt; -R6-N(R^)C[=NC(0)0R4].N(R4&gt; C(0)OR^ . -R6.N(R^&gt;R^N(R^)R5 , .R6^C(0R4)R5 . UNCOIL、·ΑΝ(Ι15&gt;Ι16 视5、_r6 _s叫 r4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，J或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、鹵烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 128409 -55- 200836743 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起 雙，形成視情況經取代之 N-雜環基或視情況經取代之N•雜芳美· 各R6為直接鍵結 '視情況經取代之直鏈或分枝狀次烧基 鍵、視情況經取代之直鏈或分枝狀次稀基鍵或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次烯基鍵或直 鏈或分枝狀次快基鏈。 礼一種式①化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 藥物在哺乳動物中治療高膽固醇血症之用 〇 ’、Wherein: η is 1 to 4; Q is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkyl, alkenyl, Tetraalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl ,heterocyclylalkenyl,heterocyclylalkynyl,heteroaryl,heteroarylalkyl,heteroarylalkenyl,heteroarylalkynyl, _R6_CN, -R6-N02, -R6_OR5, _R6 face N (R4 ) R5, _R6_s(〇)pR4, _r6 _c(〇)r4, -R6-C(S)R4, -R6-C(R4)2C(〇)R5, _R6-C(〇)〇r4, r6 〇c (〇)r4, ~R6 O(S)OR4, -R6 -C(0)N(R4)R5, -R6 -C(S)N(R4)R5, -R6-N(R5)C(〇) R4, -R6-N(R5)C(8)R4, hn(r5)c(〇)〇r4, 128409-53 - 200836743 -r6-n(r5)c(s)or4, -r6-n(r5)c(o n(r4)r5, -rln(R5)c(s&gt; N(R4)R5, -R6 _n(r5)s(〇)t r4, _r6 _n(r5 )s(〇)tn(r4 )r5, _R6 -S(0)t N(R4 )R5, _R6 -N(R5 )c(=nr5 )N(R4 )r5 and _R6 _n(r5 )c(_ C(R4)R5)N(R4)R5 , wherein each p is independently 〇, 1 or 2, and each t is independently 1 or 2; or two The adjacent R1 groups together with the carbon or heterocyclic atom to which they are directly attached may form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl, and the remaining R1 groups, if present R2 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl Alkyl, aralkenyl, arylalkynyl, heterocyclyl 'heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroaryl Alkynyl; R3 is hydrogen, alkyl, alkenyl, alkynyl, dentate alkyl, haloalkenyl 'dentynyl, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkane Radical, aryl, aryl, aralkenyl, aryl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroaryl, a heteroarylalkenyl group, a heteroarylalkynyl group, _R7-N(R4)R5 or _R7-n(r4)c(o)or4; wherein a cycloalkyl group, a cycloalkylalkyl group, a cycloalkylalkenyl group, Cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclyl a heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkane Alkyl, alkenyl, alkynyl, 128409-54-200836743 halo, i-alkyl, alkenyl, haloalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally Substituted cycloalkylenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted Arylalkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally Substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, _R6_CN, _R6-N〇2, _r6_〇r5 -R6-0C(0)R4 &gt; -R6-0S(0)2R4 &gt; -R6-C(0)R4 &gt; -r6-c(〇)〇r4 &gt; -R6-C(0)N (R4) R5, -R6_N(R4)R5, _r6_n(r5)c( )r4, -R6-N(R5)C(0)0R4 &gt; -R6-N(R5)C(0)N(R4)R5 . .Κ6.Ν(Κ5}. S(0)tR4, _R6- N[S(0)tR4]2, -r6_n(r5)c(;=nr5)n(r4)r5, -R6.N(R5)C(=NR5)N(R^)CN &gt; -R6- N(R^)C[=NC(0)0R4].N(R4&gt; C(0)OR^ . -R6.N(R^&gt;R^N(R^)R5 , .R6^C(0R4 R5 . UNCOIL, ·ΑΝ(Ι15&gt;Ι16 视5, _r6 _s is called r4 and -R6-S(0)tN(R4)R5, wherein each p-system is independently 〇, J or 2, and each t-series is independent 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted Cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted Aryl and optionally 128409-55-200836743 substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or, as appropriate, substituted N•杂芳美· Each R6 is a direct bond 'linear or branched sub-burning bond, as appropriate a linear or branched sub-alkenyl bond or a linear or branched subalkynyl chain optionally substituted; and R7 is a linear or branched sub-alkyl chain, a straight chain or a branched A secondary alkenyl bond or a linear or branched sub-fast chain. A compound of formula 1 as a stereoisomer, palmosome, tautomer or mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating hypercholesterolemia in a mammal Use 〇', .R3 N Ο) 、R2 其中： η為1至4 ; Q、 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氫、烷基、烯基、炔基、^基、_烷 基、齒烯基、齒炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烧基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R、CN、 -R6-N〇2、-R6_〇R5 …R6_n(r4)r5 _r6 名(〇)pR4、r6 _c(〇)r4、 128409 -56- 200836743 -R6 麵C(S)R4、-R6 -C(R4 )2 C(0)R5、-R6 -C(0)0R4、-R6 -0C(0)R4、 -R6-C(S)OR4 、-R6-C(0)N(R4)R5 、-R6-C(S)N(R4)R5 、 -R6-N(R5)C(0)R4、-R6-N(R5)C(S)R4、-R6-N(R5)C(0)0R4、 -R6-N(R5)C(S)OR4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)C(S&gt; N(R4 )R5、-R6 -N(R5 )S(0)t R4、-R6 _N(R5 )S(0)tN(R4 )R5、 -R6 -S(0)t N(R4 )R5、-R6 -N(R5 )C(=NR5 )N(R4 )R5 及-R6 -N(R5 )C(N= C(R4)R5)N(R4)R5，其中各p係獨立為0, 1或2，且各t係獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R為氫、烧基、浠基、炔基、鹵烧基、鹵稀基、_炔基、 環烧基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R為氫、烧基、烯基、炔基、齒烧基、_稀基、_炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烧基雜务基稀基、雜芳基炔基、-R7-N(R4)R5或 _R7_n(r4)c(o)or4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 务基务烧基、芳細基、芳炔基、雜環基、雜環基 128409 -57- 200836743 燒基、雜環基烯基、雜環基炔基、雜芳基、雜芳燒 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烧基、烯基、快基、 鹵基_烷基、函烯基、鹵炔基、視情況經取代之 %烷基、視情況經取代之環烷基烷基、視情況經取 代之％烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烷基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳燒基、視情況經取代之雜芳基烯基、視情況經 取代之雜方基快基、_r6_cn、-、-R6-〇R5、 -r6-〇c(〇)r4、-R6-〇s(〇)2R4、-R6-C(0)R4、-R6_c(0)0R4、 -R6-C(〇)N(R4)R5、_R6_N(r4)r5、_r6n(r5)c(〇)r4、 -R6-N(R5)C(〇)〇R4、_R6-N(R5)C(〇)n(r4)r5、_r6 _n(r5)_ S(〇)tR4、-R6-N[S(0)tR4]2、-R6-N(R5)c(=NR5)N(R4)R5、 -R6-N(R5)C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0)0R4]-N(R4&gt; C(0)0R4 , .R6.N(R5&gt;R7-N(R4)R5 . -R6-N=C(OR4)R5 . -R6 -N=C(R4 )R5、-R6-N(R5 )_R6-OR5、-R6_S(〇)pR4 及 -R6 -S(0)tN(R4 )R5，其中各p係獨立為〇，1或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 私烧基、烷氧烷基、視情況經取代之環烷基、視情況 128409 -58 - 200836743 經取代之環烷基烷基、視情況經取代之芳基、視情況 t取代之芳烧基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N·雜環基或視情況經取代之队雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 42·—種式⑴化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 藥物在哺乳動物中治療良性攝護腺增生之用途， 〇.R3 N Ο), R2 wherein: η is 1 to 4; Q is a fused aryl or a fused heteroaryl; each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and -alkyl,dental alkenyl,dentynyl,cycloalkyl,cycloalkylalkyl,cycloalkylalkenyl,cycloalkylalkynyl,aryl,aralkyl,arylalkenyl,arylalkynyl, hetero Cyclo, heterocyclyl, heterocyclyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, _R, CN, -R6-N 〇2, -R6_〇R5 ... R6_n(r4)r5 _r6 Name (〇) pR4, r6 _c(〇)r4, 128409 -56- 200836743 -R6 Face C(S)R4, -R6 -C(R4)2 C(0)R5, -R6 -C(0)0R4, -R6 -0C(0)R4, -R6-C(S)OR4, -R6-C(0)N(R4)R5, -R6-C (S)N(R4)R5, -R6-N(R5)C(0)R4, -R6-N(R5)C(S)R4, -R6-N(R5)C(0)0R4, -R6 -N(R5)C(S)OR4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt;-R6-N(R5)C(S&gt;N(R4)R5, -R6 - N(R5 )S(0)t R4, -R6 _N(R5 )S(0)tN(R4 )R5, -R6 -S(0)t N(R4 )R5, -R6 -N(R5 )C( =NR5 ) N(R4 )R5 and -R6 -N(R5 )C(N= C(R4)R5)N(R4)R5, wherein each p-system is independently 0, 1 or 2, and each t-series is independently 1 or 2; Or two adjacent R1 groups together with the carbon or heterocyclic atom to which they are directly attached may form a fused ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl, and the remaining R1 groups , if present, are as described above; R is hydrogen, alkyl, decyl, alkynyl, haloalkyl, halo, ynkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl Alkyl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl Or a heteroarylalkynyl group; R is hydrogen, alkyl, alkenyl, alkynyl, dentate, _thyl, ethynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylene , cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, hetero Aryl-based hydroxy group, heteroarylalkynyl, -R7-N(R4)R5 or _R7_n(r4)c(o)or4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylene , cycloalkylalkynyl, ketone alkyl, aryl, aralkynyl, heterocyclyl, heterocyclyl 128 409-57-200836743 A pyridyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents a substituent selected from the group consisting of alkyl, alkenyl, fast radical, halo-alkyl, alkenyl, haloalkynyl, optionally substituted alkyl, optionally substituted cycloalkylalkyl, optionally Substituted % alkylalkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally Substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally Substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroaryl, _r6_cn, -, -R6-〇R5, - R6-〇c(〇)r4, -R6-〇s(〇)2R4, -R6-C(0)R4, -R6_c(0)0R4, -R6-C(〇)N(R4)R5, _R6_N( R4)r5, _r6n(r5)c(〇)r4, -R6-N(R 5) C(〇)〇R4, _R6-N(R5)C(〇)n(r4)r5, _r6 _n(r5)_ S(〇)tR4, -R6-N[S(0)tR4]2 -R6-N(R5)c(=NR5)N(R4)R5, -R6-N(R5)C(=NR5)N(R4)CN ^ -R6-N(R5)C[=NC(0) 0R4]-N(R4&gt; C(0)0R4, .R6.N(R5&gt;R7-N(R4)R5 . -R6-N=C(OR4)R5 . -R6 -N=C(R4 )R5, -R6-N(R5)_R6-OR5, -R6_S(〇)pR4 and -R6 -S(0)tN(R4)R5, wherein each p-system is independently 〇, 1 or 2, and each t-system is independently 1 Or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, aryl, alkoxyalkyl, optionally substituted cycloalkyl, optionally 128409-58 - 200836743 Substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally Substituted heteroaryl and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N. heterocyclyl or, as appropriate, substituted Aryl; each R6 is a direct-bonded, optionally substituted linear or branched alkylene chain, optionally substituted a chain or branched subalkenyl chain or an optionally substituted linear or branched nalynyl chain; and R is a linear or branched alkylene chain, a linear or branched subalkenyl chain Or a linear or branched subalkynyl chain. 42. A compound of formula (1) as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for treating benign in a mammal Use of prostate gland hyperplasia, 〇 其中： η為1至4 ; Q. 為稠合芳基或稠合雜芳基； 各111係獨立選自包括氯、烧基、稀基、块基、函基、鹵燒 基、鹵烯基、_炔基、環烷基、我基烷基、環烷基 烯基、環烧基块基、芳基、芳院基、芳烯基、芳块基、 128409 -59- 200836743 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R6_CN、 •R6-N〇2、-R6-〇R5、_R6_N(R4)R5、，s(〇)pR4、_r6_c(〇)r4、 -R6-C(S)R4 ^ -R^C(R4)2C(0)R^ &gt; .R6.C(0)〇R4 . .R6.〇c(〇)R4 , -R6 -C(S)OR4、-R6 -C(0)N(R4 )R5、此 _C⑻n(r4 )r5、 -R6-N(R5)C(0)R4、-R6_n(r5)c⑻r4、_r6 娜5)c(〇)〇r4、 -R6-N(R5 )C(S)OR^ &gt; -R6-N(R5)C(0)N(R4)R5 . .R6 .N(R5 )C(S&gt; N(R4)r5、_R6_N(R5)s(〇)tR4 …R6_N(R5)s(〇)tN(R4 妒、 -R6 -S(0)t N(R4 )R5、-R6 )c(=nr5 )n(r4 )r5 及 _r6 罐5 柯知 C(R4)R5)N(R4)R5 ’其中各p係獨立為〇, i或2，且各t係獨 立為1或2 ; 或兩個相鄰Ri基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基 '雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、豳烯基、_炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基烯基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氳、烷基、烯基、炔基、鹵烷基、函烯基、南炔基、 搜烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烷基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 燒基 雜务基細基、雜芳基炔基、或 128409 -60- 200836743 -R7-N(R4)C(0)OR4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 方基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 烧基、雜環基烯基、雜環基炔基、雜芳基、雜芳烧 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 鹵基、_烷基、_烯基、函炔基、視情況經取代之 環烧基、視情況經取代之環烷基烷基、視情況經取 代之環烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烧基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜方基快基、、-R6-N〇2、-RG-OR5、 -r6-〇c(o)r4、-R6_0S(0)2R4、-r6-c(0)r4、-r6 -C(〇)〇r4、 -R6 -C(0)N(R4 )R5、_R6 _N(R4 )r5、_r6 _n(r5 )c(〇)r4、 -R6-N(R5)C(0)〇R4、-R6-N(R5)C(〇)N(R4)R5、-R6-N(R5)- S(0)tR4、_R6_N[S(0)tR4]2、-RLN(R5)C(=NR5)N(R4)R5、 -R6-N(R5 )C(=NR5 )N(R4 )CN ^ -R6-N(R5)C[=NC(0)0R4].N(R4&gt; C(0)0R4、-R6 -N(R5 )-R7 -N(R4 )R5、_r6 -N=c(〇R4 )R5、 -R6-N=C(R4)R5、-R6-N(R5)-R6_〇r5、-R6-S(〇)pR4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，i或2，且各^ 128409 -61 - 200836743 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、燒基、稀基、炔基、_燒基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R 14 R和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烷基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 43.種式（I)化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 藥物在哺乳動物中治療搔癢病之用途，Wherein: η is 1 to 4; Q. is a fused aryl or a fused heteroaryl; each 111 is independently selected from the group consisting of chlorine, alkyl, dilute, block, functional, haloalkyl, haloalkenyl , alkynyl, cycloalkyl, myalkyl, cycloalkylalkenyl, cycloalkyl, aryl, aryl, aralkenyl, aryl, 128409-59-200836743 heterocyclyl, Heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, _R6_CN, R6-N〇2, -R6 -〇R5, _R6_N(R4)R5,, s(〇)pR4, _r6_c(〇)r4, -R6-C(S)R4^-R^C(R4)2C(0)R^ &gt; .R6. C(0)〇R4 . .R6.〇c(〇)R4 , -R6 -C(S)OR4, -R6 -C(0)N(R4 )R5, this _C(8)n(r4 )r5, -R6- N(R5)C(0)R4, -R6_n(r5)c(8)r4, _r6 Na 5)c(〇)〇r4, -R6-N(R5)C(S)OR^ &gt; -R6-N(R5) C(0)N(R4)R5 . .R6 .N(R5 )C(S&gt; N(R4)r5, _R6_N(R5)s(〇)tR4 ...R6_N(R5)s(〇)tN(R4 妒, -R6 -S(0)t N(R4)R5, -R6)c(=nr5)n(r4)r5 and _r6 can 5 Kyo C(R4)R5)N(R4)R5 'where each p-system Independently 〇, i or 2, and each t is independently 1 or 2; or two adjacent Ri groups Together with the carbon or heterocyclic atom to which they are directly attached, a fused ring may be formed, selected from cycloalkyl, aryl 'heterocyclyl or heteroaryl, and the remaining R1 groups, if present, are as described above; R2 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, nonenyl, ynkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aralene Alkyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 Is hydrazine, alkyl, alkenyl, alkynyl, haloalkyl, alkenyl, alkynyl, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, Aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkylidene , heteroaryl alkynyl, or 128409 -60-200836743 -R7-N(R4)C(0)OR4; wherein cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, square Base, aralkyl, aralkenyl, arylalkynyl, heterocyclic, heterocyclic The group, heterocyclylalkenyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl may be optionally substituted by one or more substituents selected from the group consisting of Alkyl, alkenyl, alkynyl, halo, _alkyl, alkenyl, alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted ring Alkyl alkenyl, optionally substituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl , optionally substituted heterocyclic group, optionally substituted heterocyclic alkyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl a heteroarylalkyl group, optionally substituted heteroarylalkenyl group, optionally substituted heteroaryl group, -R6-N〇2, -RG-OR5, -r6- 〇c(o)r4, -R6_0S(0)2R4, -r6-c(0)r4, -r6 -C(〇)〇r4, -R6 -C(0)N(R4)R5, _R6 _N(R4 )r5, _r6 _n(r5 )c(〇)r4, -R6-N(R5)C(0)〇R4, -R 6-N(R5)C(〇)N(R4)R5, -R6-N(R5)-S(0)tR4, _R6_N[S(0)tR4]2, -RLN(R5)C(=NR5) N(R4)R5, -R6-N(R5)C(=NR5)N(R4)CN^-R6-N(R5)C[=NC(0)0R4].N(R4&gt; C(0)0R4 , -R6 -N(R5)-R7 -N(R4)R5, _r6 -N=c(〇R4)R5, -R6-N=C(R4)R5, -R6-N(R5)-R6_〇 R5, -R6-S(〇)pR4 and -R6-S(0)tN(R4)R5, wherein each p is independently 〇, i or 2, and each ^128409 -61 - 200836743 is independently 1 or 2 Each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, dilute, alkynyl, azolyl, hydroxyalkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted naphthenic An alkyl group, optionally substituted aryl group, optionally substituted aralkyl group, optionally substituted heterocyclic group, optionally substituted heterocyclylalkyl group, optionally substituted heteroaryl group and Optionally substituted heteroarylalkyl; or R 14 R together with the nitrogen to which they are attached, form an optionally substituted N-heterocyclyl or optionally substituted heteroaryl; each R 6 is a direct bond a linear or branched subalkyl chain substituted, optionally substituted, in the form of a straight chain or a branched An alkenyl chain or an optionally substituted straight or branched nalkenyl chain; and R is a linear or branched alkylene chain, a straight or branched subalkenyl chain or a straight chain or a branched Alkynyl chain. 43. A compound of the formula (I) as a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating itching in a mammal Use of disease, 其中： η為1至4 ; Q 為稠合芳基或稠合雜芳基； 128409 -62- 200836743 各R1係獨立選自包括氫、烷基、烯基、炔基、鹵基、^烷 基、i烯基、li炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 芳基、雜芳烷基、雜芳基烯基、雜芳基炔基、_R6 _CN、 -R6-N〇2、-R6-OR5、_R6_N(r4)r5、-R6_s(〇)pR4、r6 _c(〇)r4、 -R6 -C(S)R4、-R6 -C(R4 )2 C(0)R5、-R6 -C(0)0R4、_r6 _〇c(〇)r4、 -R6 -C(S)OR4、-R6 -C(0)N(R4 )R5、-R6 -C(S)N(R4 )R5、 -R6-N(R5 )C(S)OR4 ^ -R6-N(R5 )C(0)N(R4 )R5 &gt; -R6-N(R5 )C(S&gt; N(R4)R5、-R6_N(R5)s(〇)tR4、-R6-N(R5)s(〇)tN(R4)R5、 -R6 -S(0)tN(R4 )R5、-R6 _N(R5 )C(=NR5 )N(R4 )R5 及 _R6 -N(r5 )C(N== C(R4)R5)N(R4)R5，其中各p係獨立為〇, i或2，且各t係獨 立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起，可形成稠合環，選自環烷基、芳基、雜環基或雜 I 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烧基、烯基、快基、鹵烧基、鹵稀基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烧基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基稀基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 基炔基； R3為氫、烧基、烯基、炔基、_烧基、_浠基、鹵炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烧基 128409 -63- 200836743 炔基、芳基、芳烷基、 環基烷基、雜環基烯基 烧基、雜芳基浠基、 -R7-N(R4)C(0)0R4 ； 芳烯基、芳炔基、雜環基、雜 、雜環基炔基、雜芳基、雜芳 雜芳基快基、_R7_N(R4)R5或 其中—環烧基、環烧錢基、環縣稀基、環烧基快基、 芳基、芳燒基、芳烯基、芳絲、雜環基、雜環基 烧基、雜環基烯基、雜環基快基、雜芳基、雜芳燒 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代，取代基選自包括烷基、烯基、炔基、 鹵基、A烷基、鹵烯基、_炔基、視情況經取代之 環烷基、視情況經取代之環烷基烷基、視情況經取 代之裱烷基烯基、視情況經取代之環烷基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 况經取代之芳烯基、視情況經取代之芳炔基、視情 況經取代之雜環基、視情況經取代之雜環基烷基、 視情況經取代之雜環基稀基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烷基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、-R6-CN、-R6-N02、-R6-OR5、 &quot;R6-0C(0)R4 ^ -R6.〇S(0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 ^ -R6 -C(0)N(R4 )R5、-R6 -N(R4 )R5、-R6 -N(R5 )C(0)R4、 -R6-N(R5)C(0)0R4、-r6_n(R5)C(0)N(R4)R5、_R6-N(R5)-S(0)tR4、-R6-N[S(0)tR4]2、-R6-N(R5)C(=NR5)N(R4)R5、 -R6-N(R5)C(=NR5)N(R4)CN ' -R6-N(R5)C[=NC(0)0R4]-N(R4)- 128409 -64- 200836743 C(0)0R4、_r6_n(r5&gt;r7_n(r4)r5、R6 n=c_4 妒 -R6养C(R4)R5、_R6_N(R5)_R6_〇R5、^ s(〇)pR4 及 -R6-S(〇)tN(R4)R5，其中各p係獨立為〇, ，且各t 係獨立為1或2 ;Wherein: η is 1 to 4; Q is a fused aryl or a fused heteroaryl; 128409 - 62- 200836743 each R1 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halo, alkyl , i alkenyl, lialkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, aralkynyl, heterocyclic, Heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, _R6_CN, -R6-N〇2, - R6-OR5, _R6_N(r4)r5, -R6_s(〇)pR4, r6 _c(〇)r4, -R6 -C(S)R4, -R6 -C(R4)2 C(0)R5, -R6 - C(0)0R4, _r6 _〇c(〇)r4, -R6 -C(S)OR4, -R6 -C(0)N(R4)R5, -R6 -C(S)N(R4)R5, -R6-N(R5)C(S)OR4^-R6-N(R5)C(0)N(R4)R5 &gt;-R6-N(R5)C(S&gt; N(R4)R5, -R6_N (R5)s(〇)tR4, -R6-N(R5)s(〇)tN(R4)R5, -R6 -S(0)tN(R4)R5, -R6 _N(R5)C(=NR5 ) N(R4)R5 and _R6 -N(r5)C(N== C(R4)R5)N(R4)R5, wherein each p-system is independently 〇, i or 2, and each t-system is independently 1 or 2 ; or two adjacent R 1 groups and one of the carbon or heterocyclic atoms directly bonded to them , forming a fused ring selected from cycloalkyl, aryl, heterocyclic or hetero Iaryl, and the remaining R1 groups, if present, are as described above; R2 is hydrogen, alkyl, alkenyl, fast radical , haloalkyl, halo, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, arylalkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclic Alkyl, heterocyclyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl; R3 is hydrogen, alkyl, alkenyl, alkynyl, Alkyl, aryl, arylalkyl, cycloalkyl, cycloalkyl, cycloalkyl, cycloalkyl Cycloalkyl, heterocyclylalkenyl, heteroaryl fluorenyl, -R7-N(R4)C(0)0R4; aralkenyl, arylalkynyl, heterocyclyl, hetero, heterocyclyl alkyne , heteroaryl, heteroarylheteroaryl, _R7_N(R4)R5 or wherein -cycloalkyl, cyclohexane, cycloaliphatic, cycloalkyl, aryl, aryl, aromatic Alkenyl, aryl, heterocyclic, heterocyclyl, heterocyclyl, heterocyclyl A heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroarylalkynyl group may be optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, alkane Alkyl, haloalkenyl, ynkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted alkynylalkenyl, optionally substituted cycloalkylalkyne Alkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted heterocyclyl, optionally substituted Heterocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally Substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N02, -R6-OR5, &quot;R6-0C(0)R4^-R6.〇S (0)2R4 &gt; -R6-C(0)R4 ^ -R6-C(0)0R4 ^ -R6 -C(0)N(R4 )R5, -R6 -N(R4 )R5, -R6 -N (R5)C(0)R4, -R6-N(R5)C(0)0R4, -r6_n(R5)C(0)N(R4)R5, _R6-N(R5)-S(0)tR4, - R6-N[S(0)tR4]2, -R6-N(R5)C(=NR5)N(R4)R5, -R6-N(R5)C(=NR5)N(R4)CN ' -R6 -N(R5)C[=NC(0)0R4]-N(R4)- 128409 -64- 200836743 C(0)0R4, _r6_n(r5&gt;r7_n(r4)r5, R6 n=c_4 妒-R6 raise C (R4) R5, _R6_N(R5)_R6_〇R5, ^s(〇)pR4 and -R6-S(〇)tN(R4)R5, wherein each p-system is independently 〇, and each t-system is independently 1 Or 2; 各R4與R5係獨立選自包括氫'烷基、烯基、炔基、鹵烷基、 經烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烷基、視情況經取代之雜環基、視情況經 取代之雜環基烷基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之N—雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R為直鏈或分枝狀次烧基鏈、直鏈或分枝狀次烯基鏈或直 鏈或分枝狀次炔基鏈。 44·種式（I)化合物作為其立體異構物、對掌異構物、互變異 構物或其混合物或其藥學上可接受之鹽、溶劑合物或前體 藥物在哺乳動物中治療癌症之用途， 其中： 128409 〇Each R4 and R5 are independently selected from the group consisting of hydrogen 'alkyl, alkenyl, alkynyl, haloalkyl, alkyl, alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl. Alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, and optionally substituted a substituted heteroarylalkyl group; or R4 together with R5 and the nitrogen to which they are attached form an optionally substituted N-heterocyclic group or an optionally substituted N-heteroaryl group; each R6 is directly Bonded, optionally substituted straight or branched subalkyl chain, optionally substituted linear or branched subalkenyl chain or optionally substituted linear or branched nalkyne chain And R is a linear or branched sub-alkyl chain, a linear or branched subalkenyl chain or a linear or branched subalkynyl chain. 44. A compound of the formula (I) as a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or prodrug thereof for treating cancer in a mammal Uses, of which: 128409 〇 -65- 200836743 η為1至4 ; Q 為稠合芳基或稠合雜芳基； 各R1係獨立選自包括氳、烷基、烯基、炔基、_基、鹵烷 基、A烯基、齒炔基、環烷基、環烷基烷基、環烷基 烯基、環烷基炔基、芳基、芳烷基、芳烯基、芳炔基、 雜環基、雜環基烷基、雜環基烯基、雜環基炔基、雜 方基、雜务烧基、雜芳基烯基、雜芳基快基、_r6 、 -R6-N02 &quot; -R6-OR5 - -R6-N(R4)R5 &gt; -R6-S(0)pR4 ^ -R6-C(0)R4 ^ -R6-C(S)R4、-R6-C(R4)2C(〇)R5、_R6_C(〇)〇r4、_r6 〇c(〇)r4、 -R6 -C ⑸ OR4、-R6 _C(0)N(R4 )R5、-R6 _C(S)N(R4 )R5、 -R6-N(R5)C(0)R4、-R6-N(R5)C(S)R4、-R6_N(R5)c(〇)〇R4、 -R6-N(R5)C(S)OR4 &gt; -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)C(S&gt; N(R4 )R5、-R6 _N(R5 )S(〇)t R4、-R6 -N(R5 )s(〇)t n(r4 )r5、 氓6 -S(0)t N(R4 )R5 、 -R6 -N(R5 )C(=NR5 )n(R4 )R5 及 Hn(r5)c(n=c(r4)r5)n(r4)r5，其中各 p 係獨立為 〇, 1 或 ί ' ’ 2，且各t係獨立為1或2 ; 或兩個相鄰R1基團和彼等所直接連接之碳或雜環原子一 起’可形成稠合環，選自環烧基、芳基、雜環基或雜 芳基，而其餘R1基團，若存在則均如上述； R2為氫、烷基、烯基、炔基、鹵烷基、鹵烯基、鹵炔基、 環烷基、環烷基烷基、環烷基烯基、芳基、芳烷基、 芳烯基、芳炔基、雜環基、雜環基烷基、雜環基稀基、 雜環基炔基、雜芳基、雜芳烷基、雜芳基烯基或雜芳 128409 -66- 200836743 基炔基； R3為氫、烷基、烯基、炔基、A烷基、ώ烯基、_炔基、 羥烷基、環烷基、環烷基烷基、環烷基烯基、環烷基 炔基、芳基、芳烧基、芳烯基、芳炔基、雜環基、雜 環基烷基、雜環基烯基、雜環基炔基、雜芳基、雜芳 烷基、雜芳基烯基、雜芳基炔基、_R7_N(R4)R5或 -R7-N(R4)C(0)0R4 ; 其中環烷基、環烷基烷基、環烷基烯基、環烷基炔基、 芳基、芳烷基、芳烯基、芳炔基、雜環基、雜環基 院基、雜環基稀基、雜環基炔基、雜芳基、雜芳燒 基、雜芳基烯基或雜芳基炔基可視情況被一或多個 取代基取代’取代基選自包括烧基 '烯基、炔基、 鹵基、ifi烧基、鹵烯基、_快基、視情況經取代之 環烷基、視情況經取代之環烷基烷基、視情況經取 代之環烧基稀基、視情況經取代之環燒基炔基、視 情況經取代之芳基、視情況經取代之芳烷基、視情 況經取代之芳烯基、視情況經取代之芳炔基、視情 况經取代之雜環基、視情況經取代之雜環基烧基、 視情況經取代之雜環基烯基、視情況經取代之雜環 基炔基、視情況經取代之雜芳基、視情況經取代之 雜芳烧基、視情況經取代之雜芳基烯基、視情況經 取代之雜芳基炔基、-R6-CN、-R6-N〇2、_R6_〇R5、 -R6-0C(0)R4、-R6-〇S(〇)2R4、-R6-C(〇)R4、_r6 c(〇)〇r4、 -R6-C(0)N(R4)R5、_R6-N(R4)r5、-R6N(R5)c(〇)R4、 128409 -67- 200836743 -R6-N(R5)C(0)0R4 ^ -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)-S(0)tR4、-R6-N[S(0)tR4]2、-R6-N(R5)C(=NR5)N(R4)R5、 -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)^ C(0)OR4 &gt; -R6-N(R5&gt;R7-N(R4)R5 &gt; -R6-N=C(OR4)R5 &gt; -R6-N=C(R4)R5 、-r6-n(r5)-r6-or5 、-r6-s(o)pr4 及 -R6-S(0)tN(R4)R5，其中各p係獨立為〇，1或2，且各t 係獨立為1或2 ; 各R4與R5係獨立選自包括氫、烷基、烯基、炔基、_烷基、 羥烷基、烷氧烷基、視情況經取代之環烷基、視情況 經取代之環烷基烷基、視情況經取代之芳基、視情況 經取代之芳烧基、視情況經取代之雜環基、視情況經 取代之雜環基烧基、視情況經取代之雜芳基及視情況 經取代之雜芳烷基； 或R4與R5和彼兩者所連接之氮一起，形成視情況經取代之 N-雜環基或視情況經取代之泎雜芳基； 各R6為直接鍵結、視情況經取代之直鏈或分枝狀次烷基 鏈、視情況經取代之直鏈或分枝狀次烯基鏈或視情況 經取代之直鏈或分枝狀次炔基鏈；且 R7為直鏈或分枝m基鏈、直鏈或分枝狀次烯基鍵或直 鏈或分枝狀次炔基鏈。 45·—種式（1-1)化合物·· 128409 -68- 200836743-65- 200836743 η is 1 to 4; Q is a fused aryl or fused heteroaryl; each R1 is independently selected from the group consisting of hydrazine, alkyl, alkenyl, alkynyl, yl, haloalkyl, A , alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclyl Alkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, hydroxyalkyl, heteroarylalkenyl, heteroaryl, _r6, -R6-N02 &quot; -R6-OR5 - R6-N(R4)R5 &gt; -R6-S(0)pR4 ^ -R6-C(0)R4 ^ -R6-C(S)R4, -R6-C(R4)2C(〇)R5,_R6_C (〇)〇r4, _r6 〇c(〇)r4, -R6 -C (5) OR4, -R6 _C(0)N(R4)R5, -R6 _C(S)N(R4)R5, -R6-N( R5)C(0)R4, -R6-N(R5)C(S)R4, -R6_N(R5)c(〇)〇R4, -R6-N(R5)C(S)OR4 &gt; -R6- N(R5)C(0)N(R4)R5 &gt;-R6-N(R5)C(S&gt; N(R4)R5, -R6_N(R5)S(〇)t R4, -R6 -N( R5 )s(〇)tn(r4 )r5, 氓6 -S(0)t N(R4 )R5 , -R6 -N(R5 )C(=NR5 )n(R4 )R5 and Hn(r5)c( n=c(r4)r5)n(r4)r5, where each p is independently 〇, 1 or ί ' ' 2, and each t is independently 1 or 2; or two adjacent R1 The group together with the carbon or heterocyclic atom to which they are directly attached may form a fused ring selected from a cycloalkyl group, an aryl group, a heterocyclic group or a heteroaryl group, and the remaining R1 groups, if present, are as described above. R2 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, aryl, aralkyl, aromatic Alkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclyl, heterocyclyl alkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl or heteroaryl 128409-66- 200836743 Alkynyl; R3 is hydrogen, alkyl, alkenyl, alkynyl, Aalkyl, nonenyl, ynkynyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, Cycloalkylalkynyl, aryl, arylalkyl, aralkenyl, arylalkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroaryl, heteroaralkyl a heteroarylalkenyl group, a heteroarylalkynyl group, _R7_N(R4)R5 or -R7-N(R4)C(0)0R4; wherein a cycloalkyl group, a cycloalkylalkyl group, a cycloalkylalkenyl group, Cycloalkylalkynyl, aryl, aralkyl, aralkenyl, arylalkynyl, heterocyclic a heterocyclic base group, a heterocyclic group, a heterocyclyl alkynyl group, a heteroaryl group, a heteroarylalkyl group, a heteroarylalkenyl group or a heteroaryl alkynyl group may be optionally substituted by one or more substituents' The substituent is selected from the group consisting of an alkyl group, an alkenyl group, a halogen group, an ifialkyl group, a haloalkenyl group, a hydrazino group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkylalkyl group, and an optionally substituted cycloalkylalkyl group. Substituted cycloalkyl, disubstituted cycloalkylalkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally as appropriate Substituted aralkynyl, optionally substituted heterocyclic, optionally substituted heterocyclyl, optionally substituted heterocyclylalkenyl, optionally substituted heterocyclyl alkynyl, optionally Substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkenyl, optionally substituted heteroarylalkynyl, -R6-CN, -R6-N〇2 , _R6_〇R5, -R6-0C(0)R4, -R6-〇S(〇)2R4, -R6-C(〇)R4, _r6 c(〇)〇r4, -R6-C(0)N (R4) R5, _R6-N(R4)r5, -R6N(R5)c(〇)R4, 1284 09 -67- 200836743 -R6-N(R5)C(0)0R4 ^ -R6-N(R5)C(0)N(R4)R5 &gt; -R6-N(R5)-S(0)tR4, -R6-N[S(0)tR4]2, -R6-N(R5)C(=NR5)N(R4)R5, -R6-N(R5)C(=NR5)N(R4)CN &gt; -R6-N(R5)C[=NC(0)0R4]-N(R4)^ C(0)OR4 &gt;-R6-N(R5&gt;R7-N(R4)R5&gt; -R6-N= C(OR4)R5 &gt; -R6-N=C(R4)R5, -r6-n(r5)-r6-or5, -r6-s(o)pr4 and -R6-S(0)tN(R4) R5, wherein each p is independently 〇, 1 or 2, and each t is independently 1 or 2; each R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, _alkyl, hydroxyalkane Alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aryl, optionally substituted a cyclic group, optionally substituted heterocyclic alkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; or R4 together with R5 and the nitrogen to which they are attached, as appropriate Substituted N-heterocyclyl or optionally substituted anthracene aryl; each R6 is a directly bonded, optionally substituted linear or branched alkylene chain, optionally substituted a chain or branched sub-alkenyl chain or an optionally substituted linear or branched nalynyl chain; and R7 is a linear or branched m-based chain, a straight or branched subalkenyl bond or straight Chain or branched acetylene chain. 45·—Formula (1-1) Compound·· 128409 -68- 200836743 意即2-丁基-3-[4_(四氫响落_3_基胺基）苯基]峻唾琳，聊， 為其立體異構物、對掌異構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 46· 一種醫藥組合物，其包含藥學上可接受之賦形劑與式㈣ 化合物：That is, 2-butyl-3-[4_(tetrahydrofluorin-3-ylamino)phenyl], or its stereoisomers, palmomers, tautomers or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 46. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IV): Η f 意即2-丁基-3-[4-(四氫吨以基胺基）苯基]峻唾琳部玢嗣， 為其立體異構物、對掌異構物、互變異構物或其混合物； 或其藥學上可接受之鹽、溶劑合物或前體藥物。 &gt;0Η f means 2-butyl-3-[4-(tetrahydroxylamino)phenyl], which is a stereoisomer, a palmomer, a tautomer Or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. &gt;0 其中式㈣化合物為2· 丁基姻四氯心_3·基胺幻苯基] 47.-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物或前 體藥物於藥劑製造上之用途，該藥劑係在哺乳動物中治 2、預防或改善疾病或症狀，選自包括疼痛、抑鬱、心血 官疾病、呼吸道疾^與精神病學疾病及其組合， 128409 -69- 200836743 喹唑啉-4(3H)-酮。 48.如請求項47夕ffi、人 ^ , 、 之用述，其中該疾病或症狀係選自包括神經病 原〖生疼痛、炎性疼痛、内臟疼痛、癌症疼痛、化學療法疼 痛、損傷疼痛、手術疼痛、手術後疼痛、生產疼痛、分娩 疼痛、神經發生性膀胱、潰瘍性結腸炎、慢性疼痛、持續 、痛末梢媒介之疼痛、中樞媒介之疼痛、慢性頭痛、 偏頭痛、竇房結頭痛、緊張頭痛、幻想肢疼痛、末梢神經 損傷及其組合。 49·如明求項47之用途，其中該疾病或症狀係選自包括與 有關聯之疼痛、ffiv治療所引致之神經病、三叉神經痛、 癌疹後神經痛、正常疼痛、熱敏感性、局部肉狀瘤病、刺 激性腸徵候簇、克隆氏病、與多發性硬化（MS)有關聯之疼 痛、肌萎縮性側索硬化（ALS) '糖尿病患者之神經病、末 梢神經病、關節炎、風濕性關節炎、骨關節炎、動脈粥瘤 硬化、陣發性肌緊張不足、肌無力徵候簇、肌強直、惡性 鬲熱、膽囊纖維變性、假醛固酮過多症、橫紋肌溶解、甲 狀腺機能減退症、兩極抑鬱、焦慮、精神分裂症、鈉通道 母素相關疾病、家族性肢端紅痛病、原發性肢端紅痛病、 家族性直腸疼痛、癌症、癲癇、部份與一般緊張發作、不 女寧腳部徵候簇、節律不齊、纖維肌痛、在因中風或神經 知傷所造成之絕血狀態下之神經保護、快速節律不齊、心 房纖維顫動及心室纖維顫動。 50·種式屮1)化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物或= 128409 -70· 200836743 體藥物於藥劑製造上 疼痛，其方式是在該 賴性納通道， 。之用途，該藥劑係、在哺乳動物中治療 甫乳動物巾抑制離子通量經過電壓依Wherein the compound of the formula (IV) is 2·butyltetracycline _3·ylamine phenylene] 47. The compound of the formula (IV) is as its stereoisomer, palmomer, tautomer or mixture thereof or The use of a pharmaceutically acceptable salt, solvate or prodrug thereof for the manufacture of a medicament for treating, preventing or ameliorating a disease or condition in a mammal, including pain, depression, cardiovascular disease, Respiratory disease and psychiatric diseases and combinations thereof, 128409-69-200836743 quinazoline-4(3H)-one. 48. The claim of claim 47, wherein the disease or symptom is selected from the group consisting of a neuropathy, a pain, an inflammatory pain, a visceral pain, a cancer pain, a chemotherapy pain, a pain, and a pain. Surgical pain, postoperative pain, production pain, labor pain, neurogenic bladder, ulcerative colitis, chronic pain, persistent pain, pain in the distal media, pain in the central media, chronic headache, migraine, sinus headache, Stressful headaches, imaginary limb pain, peripheral nerve damage, and combinations thereof. 49. The use of claim 47, wherein the disease or symptom is selected from the group consisting of associated pain, ffiv treatment, neuropathy, trigeminal neuralgia, post-cancerous neuralgia, normal pain, heat sensitivity, local Sarcoidosis, irritating intestinal syndrome, Crohn's disease, pain associated with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) 'neuropathy of diabetic patients, peripheral neuropathy, arthritis, rheumatism Arthritis, osteoarthritis, atherosclerosis, paroxysmal dystonia, muscle weakness syndrome, myotonia, malignant phlegm, gallbladder fibrosis, pseudoaldosteronism, rhabdomyolysis, hypothyroidism, bipolar depression , anxiety, schizophrenia, sodium channel maternal-related disease, familial acral red pain, primary acral red pain, familial rectal pain, cancer, epilepsy, partial and general tension, not female Foot syndrome, irregular rhythm, fibromyalgia, neuroprotection due to stroke or neurological damage, rapid rhythm, atrial fibrillation and Room fibrillation. 50) a compound of the formula 屮1) as a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate thereof or the compound of the formula 138409-70·200836743 The pain in the manufacture of the drug is in the way of the Nasal channel. The use of the drug system in mammals to treat sputum animal towels to suppress ion flux through voltage 其中式（1-1)化合物為2-丁美2^ 土 3_[4-(四氧p比略一基 口奎°坐淋-4(3H)-酮。 胺基）笨基] 體藥物於藥劑製造上之用途，該藥劑係在哺乳動物之細胞 中降低離子通量經^電壓依賴性鈉通道，Wherein the compound of the formula (1-1) is 2-butyr 2^ soil 3_[4-(tetraoxine p is slightly more than one base 奎 ° ° sita-4(3H)-ketone. Amino) stupid] For the manufacture of medicaments, the medicament reduces the flux of ions in a mammalian cell via a voltage-dependent sodium channel, 51·-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物 其中式㈣化合物為2-丁基各[4_(四氫吨洛題胺基）笨基] 喹唑啉-4(3H)_酮。 52.-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物或前 體藥物於藥劑製造上之用途，該藥劑係在哺乳動物中治療 高膽固醇血症， 128409 -71 - 200836743a compound of the formula (IV) as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound of the formula (IV) is 2-butyl each [ 4_(tetrahydro-tonolamine) styryl] quinazolin-4(3H)-one. 52. The use of a compound of the formula (IV) as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the manufacture of a medicament, This medicine is used to treat hypercholesterolemia in mammals, 128409 -71 - 200836743 Η 其中式（Ι·1)化合物為2_ 丁美3「4 ^ # 峻唾琳-4_-嗣。了基婚㈣風峨^基胺基偉基] 53.-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上 ^ j ^又之鹽、溶劑合物或前Η The compound of the formula (Ι·1) is 2_丁美3 "4^ #峻唾琳-4_-嗣. The base marriage (4) wind 峨 基 胺 胺 ] ] ] 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 53 a construct, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt, solvate or former thereof 體樂物於藥劑製造上之用拎，兮銥 &lt;上之用通，忒樂劑係在哺乳動物中治 良性攝護腺增生，The use of body music in the manufacture of pharmaceuticals, 兮铱 &lt;上之通, 忒乐剂 in the mammals to treat benign prostate hyperplasia, 其中式㈣化合物為2_丁基_3·[4_(四氫峨n各_3_基胺基）苯基] p奎。坐淋-4(3H)-酮。 54·-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物或前 體藥物於藥劑製造上之用途，該藥劑係在哺乳動物中治療 搔癢病，Wherein the compound of the formula (IV) is 2-butyl_3.[4_(tetrahydroanthracene each_3_ylamino)phenyl]p-quine. Sitting on -4(3H)-ketone. 54. The use of a compound of the formula (IV) as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the manufacture of a medicament, The agent is for treating scrapie in a mammal, 其中式（1-1)化合物為2-丁基-3-[4-(四氫吡咯_3-基胺基）苯美] 喹唑啉-4(3H)-酮。 128409 -72- 200836743 π-種式㈣化合物作為其立體異構物、對掌異構物、互變 異構物或其混合物或其藥學上可接受之鹽、溶劑合物或前 I樂物於藥劑製造上之用途，該藥劑係在喷乳動物中治療 癌症，The compound of the formula (1-1) is 2-butyl-3-[4-(tetrahydropyrrole-3-ylamino)phenylene]quinazolin-4(3H)-one. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; For manufacturing purposes, the medicament is for treating cancer in a mammal. -中式（I 1)化口物為2_丁基邻_(四氫吡略基胺基）苯基] 口奎唾淋-4(3Η)-酉同。 128409 •73 - 200836743 七、指定代表圖： (一) 本案指定代表圖為：（無） (二) 本代表圖之元件符號簡單說明: 八、本案若有化學式時，請揭示最能顯示發明特徵的化學式：- The formula (I 1 ) of the formula (I 1 ) is 2 -butyl o-(tetrahydropyridylamino)phenyl] phenazine saliva-4(3Η)-酉. 128409 •73 - 200836743 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the characteristics that can best show the invention. Chemical formula: 128409128409
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