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TW200539871A - Pyrimidine derivatives for the treatment of abnormal cell growth - Google Patents

Pyrimidine derivatives for the treatment of abnormal cell growth Download PDF

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TW200539871A
TW200539871A TW094115237A TW94115237A TW200539871A TW 200539871 A TW200539871 A TW 200539871A TW 094115237 A TW094115237 A TW 094115237A TW 94115237 A TW94115237 A TW 94115237A TW 200539871 A TW200539871 A TW 200539871A
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ylamino
methyl
alkyl
trifluoromethyl
dihydro
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TW094115237A
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TWI303635B (en
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Michael Joseph Luzzio
John Charles Kath
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Pfizer Prod Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Organic Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

The present invention relates to a compound of the formula 1, , wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

Description

200539871 (1) 九、發明說明 - 相關申請案之相互參照 請參見2002年12月20日申請之美國專利申請案 60/435,670(代理人案號PC25339)及2003年9月5日申請之 美國專利申請案60/500,742 (代理人案號PC259 3 7)。 【發明所屬之技術領域】 ® 本發明係有關用於治療哺乳動物之異常細胞生長（例 如癌症）之新穎的嘧啶衍生物。本發明亦有關使用該化合 物以治療哺乳動物（特別是人類）之異常細胞生長之方法， 及含有該化合物之藥學組成物。 【先前技術】 吾人均知，細胞可經由其部份的DNA轉形成致癌基因 (即，經活化後，導致惡性腫瘤細胞的形成之基因）而轉變 t 成癌細胞。許多致癌基因編碼有蛋白質，而其爲可引發細 胞轉形之畸形的酪胺酸激酶。或者，正常的原始致癌基因 的酪胺酸激酶的過度表現亦可能導致增殖性疾病，有時導 致惡性的表現型。200539871 (1) IX. Description of the invention-For cross-references to related applications, please refer to US Patent Application 60 / 435,670 (No. PC25339) filed on December 20, 2002 and US Patent filed on September 5, 2003 Application 60 / 500,742 (Attorney Case No. PC259 3 7). [Technical field to which the invention belongs] ® The present invention relates to a novel pyrimidine derivative for treating abnormal cell growth in mammals, such as cancer. The present invention also relates to a method for using the compound to treat abnormal cell growth in mammals, especially humans, and a pharmaceutical composition containing the compound. [Prior art] Everyone knows that cells can be transformed into cancer cells by transforming part of their DNA into oncogenes (ie, genes that cause the formation of malignant tumor cells after activation). Many oncogenes encode proteins, which are tyrosine kinases that cause cell deformities. Alternatively, the overexpression of tyrosine kinases in normal primitive oncogenes may also lead to proliferative diseases, sometimes leading to malignant phenotypes.

受體酪胺酸激酶是一種酵素，其跨越細胞膜且具有供 生長因子（例如表皮生長因子）用之細胞外結合區、穿透膜 區、和細胞內部份（作爲蛋白質中之磷酸專一性酪胺酸基 團及因而影響細胞增殖之激酶）。其他的受體酪胺酸激酶 包含 c-erbB-2、c-met、tie-2、PDGFr、FGFr、和 VEGFR -4- 200539871 (2) 。已知此類激酶通常畸形地表現於一般的人類癌症，例如 乳癌、胃腸道癌例如結腸癌、直腸癌或胃癌，白血病、和 卵巢癌、支氣管癌或胰臟癌。吾人亦知，具有酪胺酸激酶 活性之表皮生長因子受體（EGFR)於許多人類癌症（例如大 腦、肺、鱗狀細胞、膀胱、胃、胸部、頭和頸、食道、婦 科和甲狀腺的癌症）中突變及/或過度表現。 因此，吾人已知，受體酪胺酸激酶的抑制劑可用作爲 哺乳動物癌細胞的生長之選擇性抑制劑。例如，erb st at in ，一種酪胺酸激酶抑制劑，選擇性地減弱無胸腺的裸鼠中 之表現表皮生長因子受體（EG FR)酪胺酸激酶之移植的人類 乳腺癌的生長，但不會影響不表現EGF受體之其他癌的生 長。因此，一些受體酪胺酸激酶的選擇性抑制劑可用於治 療哺乳動物之異常細胞生長，特別是癌症。除了受體酪胺 酸激酶之外，一些非受體的酪胺酸激酶（例如FAK(局限性 黏連激酶）、lck、src、abl或絲胺酸/蘇胺酸激酶（例如細 胞週期素依賴性激酶））的選擇性抑制劑亦可用於治療哺乳 動物之異常細胞生長，特別是癌症。FAK即是已知的蛋白 質-酪胺酸激酶2，PTK2。 有力的證據顯示FAK，一種細胞質的非受體酪胺酸激 酶，於細胞-基質訊息傳導途徑中扮演重要的角色（Clark and Brugge 1995， Science 268: 233-239)，且其畸形的 活化與腫瘤之新陳代謝潛力的增加有關連（Owens et al. 1 995,Cancer Research 55 ： 2 7 5 2 - 2 7 5 5)。FA K 起先經 鑑定爲一種125 kD a的蛋白質，在經v-Src轉形的細胞內， 200539871 被高度地酪胺酸-磷酸化。而後發現FA K爲酪胺酸激酶， 位於局限性黏連組織（爲培養的細胞和其在下面的底物間 的接觸點，及劇烈的酪胺酸磷酸化作用的位置）。F A Κ是 磷酸化的，因此經由對細胞外基質（EC1VI)與整合素的結合 產生反應而被活化。最近，硏究證明FAK mRNA含量的增 加且伴隨著腫瘤的侵入性轉形和FAK表現的減弱（利用反 意寡核苷酸）會引發腫瘤細胞的胞噬作用（Xu et al.l 996，Cell Growth and Diff.7: 413-418)。除了 表現於 大部份的組織類型外，亦發現在大部份人類癌腫（特別是 於高度侵入性轉移物）中之FAK的含量會增加。 多種化合物，例如苯乙烯衍生物，亦已經顯示具有酪 胺酸激酶抑制性質。5個歐洲專利申請案，即EP 0 566 266 Al( 1 993 年 10 月 20 日公開）、EP 0 602 85 1 Al( 1 994 年 6 月22日公開）、EP 0 635 507 Al(1995年1月25日公開）、EP 0 635 498 Al(1995 年 1 月 25 日公開）和 EP 0 520 7 2 2Receptor tyrosine kinase is an enzyme that spans the cell membrane and has an extracellular binding region for growth factors such as epidermal growth factor, a transmembrane region, and an intracellular component (as a phosphate-specific casein in proteins) Amino acid groups and thus kinases that affect cell proliferation). Other receptor tyrosine kinases include c-erbB-2, c-met, tie-2, PDGFr, FGFr, and VEGFR-4-200539871 (2). Such kinases are known to be abnormally manifested in general human cancers such as breast cancer, gastrointestinal cancer such as colon, rectal or gastric cancer, leukemia, and ovarian, bronchial or pancreatic cancer. We also know that epidermal growth factor receptor (EGFR) with tyrosine kinase activity is found in many human cancers (such as cancers of the brain, lungs, squamous cells, bladder, stomach, chest, head and neck, esophagus, gynecology and thyroid ) Mutations and / or overperformance. Therefore, we know that inhibitors of receptor tyrosine kinases can be used as selective inhibitors of the growth of mammalian cancer cells. For example, erb st at in, a tyrosine kinase inhibitor, selectively attenuates the growth of human breast cancer that expresses epidermal growth factor receptor (EG FR) tyrosine kinase in athymic nude mice, but Does not affect the growth of other cancers that do not express the EGF receptor. Therefore, some selective inhibitors of receptor tyrosine kinases can be used to treat abnormal cell growth in mammals, especially cancer. In addition to receptor tyrosine kinases, some non-receptor tyrosine kinases (such as FAK (Limited Adhesion Kinase), lck, src, abl, or serine / threonine kinase (such as cyclin-dependent Selective inhibitors of sex kinases)) can also be used to treat abnormal cell growth in mammals, especially cancer. FAK is known as protein-tyrosine kinase 2, PTK2. Strong evidence shows that FAK, a cytoplasmic non-receptor tyrosine kinase, plays an important role in the cell-matrix signaling pathway (Clark and Brugge 1995, Science 268: 233-239), and its abnormal activation and tumor This is related to the increased metabolic potential (Owens et al. 1 995, Cancer Research 55: 2 7 5 2-2 7 5 5). FA K was first identified as a 125 kD a protein, and 200539871 was highly tyrosine-phosphorylated in v-Src-transformed cells. Then it was found that FA K was a tyrosine kinase, located in localized adhesion tissue (the contact point between cultured cells and the underlying substrate, and the location of intense tyrosine phosphorylation). FAK is phosphorylated and is therefore activated in response to the binding of extracellular matrix (EC1VI) to integrin. Recently, studies have shown that an increase in FAK mRNA content, accompanied by invasive transformation of tumors and weakened FAK expression (using antisense oligonucleotides), can induce phagocytosis of tumor cells (Xu et al. 1996, Cell Growth and Diff. 7: 413-418). In addition to the majority of tissue types, FAK levels have also been found to increase in most human cancers, especially in highly invasive metastases. Various compounds, such as styrene derivatives, have also been shown to have tyrosine kinase inhibitory properties. 5 European patent applications, namely EP 0 566 266 Al (published on October 20, 993), EP 0 602 85 1 Al (published on June 22, 994), EP 0 635 507 Al (1995 (Published on May 25), EP 0 635 498 Al (published on January 25, 1995) and EP 0 520 7 2 2

Al(1992年12月30日公開），係有關一些雙環衍生物，特別 是鸣唑啉衍生物，其因具有酪胺酸激酶抑制性質而具有抗 癌性質。 此外，世界專利申請案WO 92/20642 ( 1 992年11月26 曰公開）係有關作爲酪胺酸激酶抑制劑之雙-單環和雙環芳 基和雜芳基化合物，其可用於抑制異常細胞增殖。世界專 利申請案WO 96/16960( 1 9 96年6月6日公開）、W〇 96/09294(1996年 3月 6 日公開）、W0 97/30034(1997年 8 月 21日公開）、WO 98/02434(1998年1月22日公開）、W〇 200539871 (4)Al (published on December 30, 1992) is related to some bicyclic derivatives, especially oxazoline derivatives, which have anticancer properties due to their tyrosine kinase inhibitory properties. In addition, the world patent application WO 92/20642 (published November 26, 992) relates to bi-monocyclic and bicyclic aryl and heteroaryl compounds as tyrosine kinase inhibitors, which can be used to inhibit abnormal cells proliferation. World patent applications WO 96/16960 (published on June 6, 1996), WO 96/09294 (published on March 6, 1996), WO 97/30034 (published on August 21, 1997), WO 98/02434 (published on January 22, 1998), WO200539871 (4)

98/02437(1998年 1 月 22 日公開）、和 WO 98/02438 (1998 年 1月22日公開）亦有關具有相同功用之作爲酪胺酸激酶抑制 劑之經取代的雜芳族衍生物。此外，下列文獻係有關可任 意地用作爲酪胺酸激酶抑制劑之雙-單環和雙環芳基和雜 芳基化合物·· WO 03/030909、WO 03/032997、US專利申 請案 2003/0 1 8 1474、US 專利申請案 2003/0 162802、US 專 利 5,863,924、WO 03/078404、US 專利 4,507,146、WO 99/41253、WO 01/72744、WO 02/48133、US專利申請案 2002/156087、WO 02/102783、和 WO 03/063794 ° 2003年12月13日申請之美國專利申請案10/734,039( 代理人案號PC25 3 3 9A)係有關多種作爲激酶抑制劑（更明確 地是FAK抑制劑）之新穎的嘧啶衍生物。此外，2003年12 月11日申請之美國專利申請案1 0/734,21 5(代理人案號 PC25937A)更明確地係有關一嘧啶衍生物子集，即帶有5 -胺基羥吲哚者，其是酪胺酸激酶抑制劑，更特別地是FAK 抑制劑。此類化合物可用於治療異常細胞生長。 因此，對於更多之可用於治療哺乳動物之異常細胞生 長（例如癌症）之一些受體和非受體的酪胺酸激酶之選擇性 抑制劑的需求仍然存在。本發明提供新穎的嘧啶衍生物， 其爲激酶抑制劑及爲非受體的酪胺酸激酶（FAK)之抑制劑 ，且可用於治療異常細胞生長。 【發明內容】 發明總論 200539871 本發明係有關一種如下式1所示之化合物98/02437 (published on January 22, 1998) and WO 98/02438 (published on January 22, 1998) are also related to substituted heteroaromatic derivatives having the same function as tyrosine kinase inhibitors. In addition, the following documents are related to bis-monocyclic and bicyclic aryl and heteroaryl compounds that can be arbitrarily used as tyrosine kinase inhibitors. WO 03/030909, WO 03/032997, US Patent Application 2003/0 1 8 1474, US patent application 2003/0 162802, US patent 5,863,924, WO 03/078404, US patent 4,507,146, WO 99/41253, WO 01/72744, WO 02/48133, US patent application 2002/156087, WO 02/102783, and WO 03/063794 ° U.S. Patent Application No. 10 / 734,039 (Attorney Docket No. PC25 3 3 9A) filed on December 13, 2003 is related to multiple as kinase inhibitors (more specifically FAK inhibitors) ) A novel pyrimidine derivative. In addition, U.S. Patent Application No. 10 / 734,21 5 (Attorney Docket No. PC25937A) filed on December 11, 2003 is more specifically related to a subset of pyrimidine derivatives, that is, with 5-aminooxindole Or, it is a tyrosine kinase inhibitor, and more particularly a FAK inhibitor. Such compounds are useful for treating abnormal cell growth. Therefore, there is still a need for more selective inhibitors of some receptors and non-receptors of tyrosine kinases that can be used to treat abnormal cell growth in mammals, such as cancer. The present invention provides novel pyrimidine derivatives, which are kinase inhibitors and non-receptor tyrosine kinase (FAK) inhibitors, and can be used to treat abnormal cell growth. [Summary of the Invention] Summary of Invention 200539871 The present invention relates to a compound represented by the following formula 1

cf3cf3

Φ 或其藥學上可接受之鹽、溶劑化物、水合物或前驅藥 物， 其中η是1至3之整數； 各個R1是分別選自氫、羥基、-(CrCd烷基、—（(：3一 C7)環烷基、-(C2_C9)雜環基、-CHC^Ce)烷基、—〇(C3_c7；) 環烷基、-〇(C2-C9)雜環基、_NR5R6、-SR7、-SOR7、-S〇2R7 、- C〇2R12、- CONR5R6、- S02NR5R6、- NHCOR"、 - NR12C〇NR5R6、和-NR,2S02R7之取代基；其中該取代基 # 之—（crC6)烷基、-(c3-c7)環烷基、-（c2-c9)雜環基、 一0(CM6)烷基、-o(c3-c7)環烷基、-o(c2-c9)雜環基、 一NR5R6、__SR7、一S0R7、_s〇2R7、_c〇2r12、一c〇nr5r6、 - S〇2NRSR6、_NHC〇R12、一 Nr12C〇Nr5r6、和一 NRl2s〇2R7 係 任意地經1至3個分別選自氫、鹵素、羥基、-CF3、-CN 、一（Ci —C6)烷基、-NR5R6、-OR12、~(C3 - C7)環烷基、 一（C2 — C9)雜環基、-C02R12、-CONR5R6、和-CONR5R8 之基 團所取代； 各個R2是分別選自氫、-(CrC6)烷基、-(C2_C6)烯基 、一（CrC6)炔基、-(c3-c7)環烷基、-(C2_C9)雜環基、 200539871 (6) -C〇2R12、和-CONR5R6之取代基；其中該R2取代基之—（c】-• c6)烷基、-(C2-C6)烯基、-(C2-C6)炔基、-(C3-C7)環院基 ’ 、-(C2-C9)雜環基、-C〇2R12、和-CONR5R6任意地經！至3 個分別選自氫、鹵素、羥基、-CF3、-N02、-CN、-((：「 c6)焼基、-(C2-C6)嫌基、-(C2-C6)炔基、-C = N-0H、 -C = N-〇((CrC6)烷基）、-NR5r6、-〇r12、-(c3-c7)環烷基 、一（c2-c9)雜環基、一C〇2R12、—CONFER6、-CONR5R8、 ’一 SR7、一 SOR7、一 S02R7、一 S02NR5r6、-NHCOR12、 - NR12C〇NR5R6、和一 NR12S02R7之基團所取代，其中該R2基 團之- (c2-c6)烯基和-(c2-c6)炔基可任意地經1至3個R12基 團所取代； R1和R2可與相連接的原子一起形成- (c3-c1Q)環烷基 或—（C2-C9)雜環基之環狀基團，其中該環狀基團任意地經 1至3個分別選自氫、鹵素、羥基、-cf3、-n〇2、，CN、Φ or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof, wherein η is an integer from 1 to 3; each R1 is selected from hydrogen, hydroxyl,-(CrCd alkyl,-((: 3 a C7) cycloalkyl,-(C2_C9) heterocyclyl, -CHC ^ Ce) alkyl, -〇 (C3_c7;) cycloalkyl, -〇 (C2-C9) heterocyclyl, _NR5R6, -SR7, -SOR7 , -S〇2R7, -C〇2R12, -CONR5R6, -S02NR5R6, -NHCOR ", -NR12C〇NR5R6, and -NR, 2S02R7 substituents; wherein the substituent #-(crC6) alkyl,-( c3-c7) cycloalkyl,-(c2-c9) heterocyclyl, -0 (CM6) alkyl, -o (c3-c7) cycloalkyl, -o (c2-c9) heterocyclyl, -NR5R6 , __SR7, -S0R7, _s〇2R7, _c〇2r12, -cnr5r6,-S〇2NRSR6, _NHC〇R12, -Nr12C〇Nr5r6, and -NR122s〇2R7 are arbitrarily selected from 1 to 3 respectively from hydrogen , Halogen, hydroxy, -CF3, -CN, mono (Ci-C6) alkyl, -NR5R6, -OR12, ~ (C3-C7) cycloalkyl, mono (C2-C9) heterocyclyl, -C02R12,- CONR5R6, and -CONR5R8 are substituted; each R2 is selected from hydrogen,-(CrC6) alkyl,-(C2_C6) alkenyl, and (CrC6) alkyne ,-(C3-c7) cycloalkyl,-(C2-C9) heterocyclyl, 200539871 (6) -C〇2R12, and -CONR5R6 substituents; wherein the R2 substituent is-(c)-• c6) Alkyl,-(C2-C6) alkenyl,-(C2-C6) alkynyl,-(C3-C7) cycloalkyl ',-(C2-C9) heterocyclyl, -C〇2R12, and -CONR5R6 Arbitrarily passed! To 3 are selected from hydrogen, halogen, hydroxyl, -CF3, -N02, -CN,-((: "c6) fluorenyl,-(C2-C6) anhydroxyl,-(C2-C6) Alkynyl, -C = N-0H, -C = N-〇 ((CrC6) alkyl), -NR5r6, -〇r12,-(c3-c7) cycloalkyl, mono (c2-c9) heterocyclyl , -CO2R12, -CONFER6, -CONR5R8, '-SR7, -SOR7, -S02R7, -S02NR5r6, -NHCOR12,-NR12C0NR5R6, and -NR12S02R7 are replaced by the group of- c2-c6) alkenyl and-(c2-c6) alkynyl may be optionally substituted with 1 to 3 R12 groups; R1 and R2 may form together with the attached atoms-(c3-c1Q) cycloalkyl or — (C2-C9) a cyclic group of a heterocyclic group, wherein the cyclic group is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -cf3, -n02, CN,

. *~(C!-C6)院基、-(c2-C6)嫌基、_(C2-C6)炔基、-C = N- 〇H 、- C = N-〇（（Cl_c6)烷基）、-NR5R6、_〇R12、- (C3 - C7)環烷 基、—（C2-C9)雜環基、-C02R12、-CONR5R6、-CONR5R8 、-SR7、- SOR7、- S02R7、- S02NR5R6、- NHCOR12、 一NR12C〇NR5R6、和一NR12s〇2R7之基團所取代，其中該環狀 基團之-（c2-c6)烯基和-(c2-c6)炔基可任意地經1至3個R〗2 基團所取代，及該環狀基團任意地爲1至3個選自-（C = 0) 、-S02、一5一、一 〇 一、一 N_、一 NH_ 和一 NR"之單元所中斷； R3是選自下列之取代基： (a)氫； -9 - 200539871 (7) (b) -(C6-C1(})芳基或-(C^-Cg)雜芳基，而其任意地經1 • 至3個分別選自鹵素、羥基、-（CrCd烷基、-（CrCj烷 •基-P(0)(0(CrC6)烷基）2、-(C3-C1())環烷基、-(c6_c10)芳 基、-(C2-C9)雜環基、雜芳基、-NR5R6、· -NHS02(Ci_C6)烷基、-NHS02(C3-C6)環烷基、-N((C1-C6) 烷基 MSO^CrCe)烷基）、-NGCrCe)烷基）（so2(c3-c6)環烷 基）、-n((c3-c6)環烷基 KsojCi-cj 烷基）、-n((c3-c6：^ •烷基）（S02(C「C6)環烷基）、-Od-Cd烷基、-O-SOJC， C6)烷基、-o-so2(c3-c6)環烷基、-(COMCi-Cj烷基、 -(co)cf3' -(co)(c3-cl0)m^m ' -(CO)(C6-C]0)^ s ^ -(CO)(C2-C9)雜環基、-(COKC^-CJ 雜芳基、-（CCOCKCr C6)烷基、-(co)o(c3-c1())環烷基、-（co)o(c6-c1())芳基 、-(co)o(c2-c9)雜環基、-(CCOCKC】-c9)雜芳基、 -((：〇)((：!-c6)烷基-CKC^CJ 烷基-、-so2(c「c6)烷基、 - S〇2(C3 - C6)環烷基、_S02CF3、-S02NH2、-SC^NhKCrCe) B 烷基、-S02NH(C3-C6)環烷基、-S02N((C「C6)烷基）2、 -sc^NUc】-c6)烷基）（（c3-c6)環烷基）、-so2n((c3-c6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-(c6-c1())芳基 或-(c〗-C9)雜芳基任意地爲1至3個選自-S-、-0-、-N-、 -NH-和-NR12之單元所中斷； (c) -(c3-c1())環烷基、-(c2-c9)雜環基、和-((^-(^烷 基-(c2-c9)雜環基，而其任意地經1至3個分別選自鹵素、 羥基、-(C^-Ce)烷基、-(CrCj 烷基-PiOMCKC^Cd 烷基）2 、-(c3-c1())環烷基、-(c6-c1D)芳基、-(c2-c9)雜環基、 -10· 200539871 (8) -（CrCj 雜芳基、-NR5R6、-NHS02(C「C6)烷基、 -NHS02(C3-C6)環烷基、-NUCrCd 烷基 KSCMCrCj 烷基） 、-NUC^-CJ 烷基）（S02(C3-C6)環烷基）、-N((C3-C6)環烷 基）（5〇2((^_0：6)烷基）、-1^(((：3-(：6)環烷基）（5〇2((：厂(：6)環烷 基）、一OiC^Ce)院基、-〇 - SO^C^Ce)院基、-〇_S02(C3 - c6)環烷基、-(COMCrc6)烷基、-(co)cf3、-(co)(c3-c10)環烷基、-(co)(c6-c1£))芳基、-(co)(c2-c9)雜環基 、-（c〇）（c】-c9)雜芳基、-(C0)0(CrC6)烷基、 -（co)o(c3-c1())環烷基、-(co)o(c6-c1())芳基、 -（co)o(c2-c9)雜環基、-(ccocUCrCg)雜芳基、 -(COKC^-Ce)烷基-CMCrCe)烷基-、-SCMCrCe)烷基、 -S02(c3-c6)環烷基、-S02CF3、- S02NH2、-SOjjNmCi-Ce) 烷基、-so2nh(c3-c6)環烷基、-sc^NUCrc6)烷基）2、 - SC^NGCrCe)烷基）（（C3-C6)環烷基）、-S02N((C3-C6)環院· 基）2、和- so2nr5r6之基團所取代，其中該_((：3_(：1())環烷 基、_(C2_C9)雜環基、和-(CrCe)烷基-(C2-C9)雜環基任 意地爲 1 至 3個選自-(c = 0)、- S02、-S-、-〇-、-N-、 -NH-和-NR12之單元所中斷； ((^-(CrCe)烷基，而其任意地經1至3個分別選自鹵素 、羥基、-(C广C6)烷基、-(CrCJ 烷基-PiOKCUC^-Ce)烷 基）2、-(CrCw)環烷基、-(C6-C1Q)芳基、-(C2-C9)雜環基 、-（Κ9)雜芳基、-NR5R6、-NHSOjCVCd烷基、 - NHS02(C3-C6)環烷基…N((C〗〜C6)烷基烷基） 、-n((c】-c6)烷基）（so2(c3-c6)環烷基）、-N((c3-c6)環烷 -11 · 200539871 Ο) 基）（s〇2(c】-c6)烷基）、-n((c3-c6)環烷基）（s〇2(c3-c6)環烷 基）、-CKCi-Ce)院基、-0-S02(CrC6)院基、-〇-S02(C3-C6)環烷基、-(COKC^-CJ烷基、-(co)cf3、-(co)(c3-c10)環烷基、-(co)(c6-c1())芳基、-(CO)(C2-C9)雜環基 、-(COMC】-c9)雜芳基、-（ccOcKCrCe)烷基、 -（CC^CKCrCH)環烷基、-(co)o(c6-c1())芳基、 -（co)o(c2-c9)雜環基、-((:0)0((^-(^)雜芳基、 ® -((：0)((：，C6)烷基-〇(C「C6)烷基-、-SOjCrCj 烷基、 - S〇2(C3-C6)環烷基、-S02CF3、-S02NH2、- S02NH(CrC6) 烷基、-S02NH(C3_C6)環烷基、-SC^NUC^Ce)烷基）2、 - SC^NUCrCe)烷基）（（c3-c6)環烷基）、-so2n((c3-c6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-（(：广(：6)烷基任 意地爲 1至 3個選自-（C = 0)、-S02、-S-、-〇-、-N-、 - ΝΗ-和-NR12之單元所中斷； 及其中各個R3之（b)-(d)取代基、基團或單元任意地經 I 1至3個分別選自氫、鹵素、羥基、-CF3、-N02、-CN、 -(CrCj 烷基、-(C2-C6)烯基、-(C2-C6)炔基、-（C3_C7)環 烷基、-(c2-c9)雜環基、_(C6-C1())芳基、-(CrCg)雜芳基 、-CKCrCe)烷基、-0(c3 - C7)環烷基、-〇(c2-C9)雜環基 ' -C = N-〇H ' -C = N-〇((C1-C6)^ g ) ^ ~NR5R6 ' -SR7' - S〇R7、一 S02R7、_C〇2R12、_C〇NR5r6、_s〇2NR5R6、 -1^}4(：〇1^、-1^尺】2(：〇1^1^1^、和—^^1?125〇2尺7之基團所取代； R4是選自氫、-（CrCe)院基、-(C3-C7)環院基和- (C2 -C9)雜環基之取代基；其中該R4取代基之烷基、 -12· 200539871 (10) -(C3-C7)環烷基和- (c2-c9)雜環基任意地經1至3個分別選 自氫、鹵素、羥基、-(CrCj 烷基、-CN、-NR5R6、-OR5 、-(C 3 - C 7)環院基、-(C 2 - C 9)雜環基、-C O 2 R12、 -S〇2NR5R6、-NR12S02R7、_S02R7、和-CONR5R8之基團所 取代；其中該-CONR5R8中之R5和R8可與相連結的原子一 起形成-(C2-C9)雜環基；* ~ (C! -C6) courtyard,-(c2-C6) alkyl, _ (C2-C6) alkynyl, -C = N-〇H, -C = N-〇 ((Cl_c6) alkyl ), -NR5R6, _〇R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, -CONR5R8, -SR7,-SOR7,-S02R7,-S02NR5R6, -NHCOR12, a NR12C0NR5R6, and a NR12s02R7 group, wherein-(c2-c6) alkenyl and-(c2-c6) alkynyl of the cyclic group can be optionally passed through 1 to 3 Each R 2 group is substituted, and the cyclic group is arbitrarily 1 to 3 selected from-(C = 0), -S02, -5, -101, -N_, -NH_, and NR " The unit is interrupted; R3 is a substituent selected from: (a) hydrogen; -9-200539871 (7) (b)-(C6-C1 (}) aryl or-(C ^ -Cg) heteroaryl And it is optionally selected from 1 to 3 selected from halogen, hydroxyl,-(CrCd alkyl,-(CrCj alkyl • yl-P (0) (0 (CrC6) alkyl) 2,-(C3- C1 ()) cycloalkyl,-(c6_c10) aryl,-(C2-C9) heterocyclyl, heteroaryl, -NR5R6,--NHS02 (Ci_C6) alkyl, -NHS02 (C3-C6) cycloalkane Group, -N ((C1-C6) alkyl MSO ^ CrCe) alkyl), -NGCrCe) alkyl) (so2 (c3-c6) cycloalkyl ), -N ((c3-c6) cycloalkyl KsojCi-cj alkyl), -n ((c3-c6: ^ alkyl) (S02 (C 「C6) cycloalkyl), -Od-Cd alkane , -O-SOJC, C6) alkyl, -o-so2 (c3-c6) cycloalkyl,-(COMCi-Cj alkyl,-(co) cf3 '-(co) (c3-cl0) m ^ m '-(CO) (C6-C) 0) ^ s ^-(CO) (C2-C9) heterocyclyl,-(COKC ^ -CJ heteroaryl,-(CCOCKCr C6) alkyl,-(co ) o (c3-c1 ()) cycloalkyl,-(co) o (c6-c1 ()) aryl,-(co) o (c2-c9) heterocyclyl,-(CCOCKC) -c9) hetero Aryl,-((: 〇) ((:!-C6) alkyl-CKC ^ CJ alkyl-, -so2 (c "c6) alkyl, -S〇2 (C3-C6) cycloalkyl, _S02CF3 , -S02NH2, -SC ^ NhKCrCe) B alkyl, -S02NH (C3-C6) cycloalkyl, -S02N ((C "C6) alkyl) 2, -sc ^ NUc] -c6) alkyl) (( c3-c6) cycloalkyl), -so2n ((c3-c6) cycloalkyl) 2, and -so2nr5r6 are substituted with the-(c6-c1 ()) aryl or-(c〗- C9) Heteroaryl is optionally interrupted by 1 to 3 units selected from -S-, -0-, -N-, -NH- and -NR12; (c)-(c3-c1 ()) cycloalkane ,-(C2-c9) heterocyclyl, and-((^-(^ alkyl- (c2-c9) heterocyclyl, which are optionally selected from halogen, hydroxy,-( C ^ -Ce) alkyl, -(CrCj alkyl-PiOMCKC ^ Cd alkyl) 2,-(c3-c1 ()) cycloalkyl,-(c6-c1D) aryl,-(c2-c9) heterocyclyl, -10200539871 ( 8)-(CrCj heteroaryl, -NR5R6, -NHS02 (C "C6) alkyl, -NHS02 (C3-C6) cycloalkyl, -NUCrCd alkylKSCMCrCj alkyl), -NUC ^ -CJ alkyl) (S02 (C3-C6) cycloalkyl), -N ((C3-C6) cycloalkyl) (502 ((^ _ 0: 6) alkyl), -1 ^ (((: 3- (: 6) Cycloalkyl) (50 ((: Plant (: 6) cycloalkyl), -OiC ^ Ce) courtyard, -0-SO ^ C ^ Ce) courtyard, -〇_S02 (C3- c6) cycloalkyl,-(COMCrc6) alkyl,-(co) cf3,-(co) (c3-c10) cycloalkyl,-(co) (c6-c1 £)) aryl,-(co) (c2-c9) heterocyclyl,-(c0) (c) -c9) heteroaryl,-(C0) 0 (CrC6) alkyl,-(co) o (c3-c1 ()) cycloalkyl ,-(Co) o (c6-c1 ()) aryl,-(co) o (c2-c9) heterocyclyl,-(ccocUCrCg) heteroaryl,-(COKC ^ -Ce) alkyl-CMCrCe) Alkyl-, -SCMCrCe) alkyl, -S02 (c3-c6) cycloalkyl, -S02CF3, -S02NH2, -SOjjNmCi-Ce) alkyl, -so2nh (c3-c6) cycloalkyl, -sc ^ NUCrc6 ) Alkyl) 2, -SC ^ NGCrCe) alkyl) ((C3-C6) cycloalkyl), -S02N ((C3-C6) cycloalkyl · yl) 2, and -so2n substituted by a group of r5r6, wherein the _ ((:: 3 _ (: 1 ()) cycloalkyl, _ (C2_C9) heterocyclyl, and-(CrCe) alkyl- (C2-C9) heterocyclyl Is interrupted by 1 to 3 units selected from-(c = 0), -S02, -S-, -〇-, -N-, -NH-, and -NR12; ((^-(CrCe) alkyl, And it is arbitrarily selected from 1 to 3 respectively selected from halogen, hydroxyl,-(C-C6) alkyl,-(CrCJ alkyl-PiOKCUC ^ -Ce) alkyl) 2,-(CrCw) cycloalkyl,- (C6-C1Q) aryl,-(C2-C9) heterocyclyl,-(Κ9) heteroaryl, -NR5R6, -NHSOjCVCd alkyl,-NHS02 (C3-C6) cycloalkyl ... N ((C〗 ~ C6) alkylalkyl), -n ((c) -c6) alkyl) (so2 (c3-c6) cycloalkyl), -N ((c3-c6) cycloalkane-11 · 200539871 Ο) group ) (S〇2 (c) -c6) alkyl), -n ((c3-c6) cycloalkyl) (s〇2 (c3-c6) cycloalkyl), -CKCi-Ce), 0-S02 (CrC6) courtyard, -0-S02 (C3-C6) cycloalkyl,-(COKC ^ -CJ alkyl,-(co) cf3,-(co) (c3-c10) cycloalkyl, -(co) (c6-c1 ()) aryl,-(CO) (C2-C9) heterocyclyl,-(COMC) -c9) heteroaryl,-(ccOcKCrCe) alkyl,-(CC ^ CKCrCH ) Cycloalkyl,-(co) o (c6-c1 ()) aryl,-(co) o (c2-c9) heterocyclyl,-((: 0) 0 ((^ -(^) Heteroaryl, ®-((: 0) ((:, C6) alkyl-〇 (C "C6) alkyl-, -SOjCrCj alkyl, -S〇2 (C3-C6) cycloalkane Group, -S02CF3, -S02NH2, -S02NH (CrC6) alkyl, -S02NH (C3_C6) cycloalkyl, -SC ^ NUC ^ Ce) alkyl) 2, -SC ^ NUCrCe) alkyl) ((c3-c6 ) Cycloalkyl), -so2n ((c3-c6) cycloalkyl) 2, and -so2nr5r6, wherein-((:: ((6) alkyl) is optionally 1 to 3 Interrupted from-(C = 0), -S02, -S-, -〇-, -N-,-Ν-and -NR12; and (b)-(d) substituents and groups of each R3 The group or unit is arbitrarily selected from I 1 to 3 respectively selected from hydrogen, halogen, hydroxyl, -CF3, -N02, -CN,-(CrCj alkyl,-(C2-C6) alkenyl,-(C2-C6) Alkynyl,-(C3_C7) cycloalkyl,-(c2-c9) heterocyclyl, _ (C6-C1 ()) aryl,-(CrCg) heteroaryl, -CKCrCe) alkyl, -0 (c3 -C7) cycloalkyl, -〇 (c2-C9) heterocyclyl '-C = N-〇H' -C = N-〇 ((C1-C6) ^ g) ^ ~ NR5R6 '-SR7'-S 〇R7, -S02R7, _C〇2R12, _C〇NR5r6, _s〇2NR5R6, -1 ^} 4 (: 〇1 ^, -1 ^ foot) 2 (: 〇1 ^ 1 ^ 1 ^, and-^^ 1 ? 125〇2 feet 7 group; R4 is selected Substituents for hydrogen,-(CrCe) radical,-(C3-C7) ring radical and-(C2-C9) heterocyclyl; wherein the alkyl group of the R4 substituent, -12 · 200539871 (10)-( C3-C7) cycloalkyl and-(c2-c9) heterocyclyl are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl,-(CrCj alkyl, -CN, -NR5R6, -OR5,-( C 3-C 7) Cyclocyclyl,-(C 2-C 9) heterocyclyl, -CO 2 R12, -S〇2NR5R6, -NR12S02R7, _S02R7, and -CONR5R8; wherein -CONR5R8 In which R5 and R8 may form a-(C2-C9) heterocyclyl together with the linked atoms;

R5和R6各是分別選自氫、-(CrC6)烷基、-(〇3-(：7)環 烷基、-(C2-C9)雜環基、-（C6_C1())芳基、_(Ci —c9)雜芳基 、-COR12、和-S02R12之取代基；其中該R5和R6取代基之 -（C^CeH完基、-（C3_C7)環院基、-（C2-C9)雜環基、-(〇6一 C】。）芳基、-（CrC9)雜芳基、-COR”、和-s〇2Rl2任意地經 1至3個分別選自氫、鹵素、-CF3、-CN、-（CrCe)院基、 -NmCi-Cj烷基、-NH(C3-C7)環烷基、—NH(c2 —C9)雜環基 、-NH(C6-C1())芳基、-NmC^Cj 雜芳基、-NUCrCj 院基 )2、-N((C3-C7)環院基）2、-N((C2_C9)雜環基）2、_n((c6- ci0)芳基）2、-NUC^C9)雜芳基）2、-〇(c广c6)烷基、 -o(c3-c7)環烷基、_o(c2-c9)雜環基、-〇(c6 —Ci。）芳基、 一 C〇2R7、一 S〇2NR5R6、一NR12S〇2R7、—s〇2R7、一c〇NH2、 -CONHR7、和一 C〇NR7R8之基團所取代；其中該一 c0nr7r8 中之R7和R8可與相連結的氮原子一起形成-(C2-C9)雜環基 R5和R6可與相連結的原子—起形成-(C2-C9)雜環基， 其中該-（CfC：9)雜環基任意地經1至3個分別選自氫、歯素 、羥基、-CF3、-N〇2、-CN、-（Ci —Ce)烷基一（cv嫌 -13- 200539871 (11) 基、一（c2 —C6)炔基、一C = N_〇H、一 C^N-QUC^-Ce)院基）、 -NR7R8、-OR12、-（C「C7)環烷基、-(C2-C9)雜環基、 一 C〇2R12、 一 CONR7R8、一C〇NR5R8、 -SR7、一S〇R7、-S02R7 、-S02NR7R8、-NHCOR12、-NR12CONR7R8、和-NR12S02R7 之基團所取代，其中該-(C2-C9)雜環基之_(C2_C6)烯基和 -（C2_C6)炔基可任意地經1至3個R7基所取代，及該-(C2-C9)雜環基任意地爲1至3個選自-（00)、-S02、-S-、-0 -® 、-N-、-NH-和-NR12之單元所中斷； R7是選自-（Ci-Ce)焼基、-(c3-c7)環院基、-(c2-c9) 雜環基、-(c6-c1())芳基、和-(CrCd雜芳基之取代基；其 中該R7取代基之-(c〗-c6)烷基、-(c3-c7)環烷基、-(c2-c9) 雜環基、-(C6-C1())芳基、和-（CrCO雜芳基任意地經1至3 個分別選自氫、鹵素、羥基、-CN、-(Ci-Cj烷基、 _NR122、和一 〇(Ci_c6)烷基之基團所取代； I R8是選自氫、-(C^CJ烷基、-(c3-c7)環烷基、-(c2- c9)雜環基、-（C6-C1())芳基、和-(Cl-C9)雜芳基之取代基 ;其中該R8取代基之-(C丨-C6)烷基、-(C3-C7)環烷基、 一（C2-C9)雜環基、-(CVc】D)芳基、和-(c厂c9)雜芳基任意 地經1至3個分別選自氫、鹵素、羥基、-CN、-((：〗-(：6)烷 基…NH2、-NHR9、-NR92、—0R9、_(C3-C7)環烷基、 一（C2-C9)雜環基、-C〇2R1。、_c〇NH2 …c〇NHR"、和 - CONR^R11之基團所取代；其中該_c〇NRl〇Rll中之Rl。和 R11可與相連結的氮原子〜起形成_(C2-C9)雜環基； R9和R"分別各是-(Ci —C6)烷基； -14- 200539871 (12) R11是氫或_(c广C6)烷基；及 R12是選自氫、-(CrC6)烷基、-(c3-c7)環烷基、 -（c2-c9)雜環基一（C6_C1())芳基、和-(Crc9)雜芳基之取 代基；其中該R12取代基之-d-Cd烷基、-(c3_c7)環烷基 、-（c2-c9)雜環基、-(C6-C1())芳基、和-(CrCj雜芳基任 意地經1至3個分別選自氫、鹵素、-CF3、-CN、_((：厂(：6) 院基、-NhHC^-Ce)烷基、-NH(C3-C7)環烷基、-NH(C2_C9) ® 雜環基、-NH(C6-C1())芳基、-NH(C广C9)雜芳基、-N((Cr c6)烷基）2、-n((c3 - c7)環烷基）2、-n((c2-c9)雜環基）2、 -N((c6-C10)芳基）2、-NUC^Cg)雜芳基）2、-◦(CrCe)烷基 、-0(C3-C7)環烷基、-〇(C2-C9)雜環基、-〇(C6-C1())芳基 、""〇(C「C9)雜方基、-(C3-C7)環院基、-(C2-C9)雜環基 、一C02R7、一C〇NH2、一CONHR7、和一CONR7R8之基團所取 代；其中該_CONR7R8中之R7和R8可與相連結的原子一起 _ 形成_(C2_C9)雜環基。 本發明亦包含同位素標記的化合物，其與式1所示之 化合物相同，惟其中一或多個原子爲具有與天然發現的原 子量或質量數不同的原子量或質量數之原子所取代。可倂 入本發明化合物之同位素的例子包含氫、碳、氮、氧、磷 、氟和氯的同位素，分別是例如2H、3H、13C、]4C、15N、 180、17〇、31P、32P、35S、18F 和 36C1。含有上述同位素及 / 或其他原子的其他同位素之本發明之化合物、其前驅物和 該化合物或該前驅物之藥學上可接受之鹽均在本發明的範 圍內。一些本發明之同位素標記的化合物（例如含有放射 -15- 200539871 (13) 性同位素（例如3H和14 C)之化合物）可用於藥物及/或受質組 織分佈分析。氚化的同位素（即3H)和碳-14同位素（即14 C) 由於其容易製備及易偵測性因而特別適宜。此外，較重的 同位素（例如氘，即2H)的取代由於具有較大的代謝安定性 因而可提供一些治療上的優點（例如較長的活體內半生期 或較低的劑量需求），並因此在某些情況較爲適宜。本發 明之式1所示之同位素標記的化合物及其前驅物通常藉由 ® 下文之反應圖及/或實例和製備例中所揭示之步驟加以製 備，惟以立即可獲致之同位素標記劑取代非同位素標記劑 〇 本發明亦有關式1所示之化合物之藥學上可接受之酸 加成鹽。可用於製備上述本發明之齡性化合物之藥學上可 接受之酸加成鹽的酸是可形成無毒性酸加成鹽者，即含有 藥學上可接受之陰離子的鹽，例如鹽酸鹽、氫溴酸鹽、氫 碘酸鹽、硝酸鹽、硫酸鹽、硫酸氫鹽、磷酸鹽、酸式磷酸 b 鹽、乙酸鹽、乳酸鹽、檸檬酸鹽、酸式檸檬酸鹽、酒石酸 鹽、酒石酸氫鹽、琥珀酸鹽、順丁烯二酸鹽、反丁烯二酸 鹽、葡糖酸鹽、糖二酸鹽、苯甲酸鹽、甲磺酸鹽、乙磺酸 鹽、苯磺酸鹽、對甲苯磺酸鹽和pamoate [即1,1’-伸甲基-雙（2-羥基-3-萘甲酸鹽）]。 本發明亦有關式1所示之鹼加成鹽。可用作爲製備在 性質上爲酸性之式1所示之化合物之藥學上可接受之鹼鹽 之試劑的化學鹼是可與該化合物形成無毒性鹼鹽者。所述 之無毒性鹼鹽包含（但不限於）由例如鹼金屬陽離子（例如鉀 -16- 200539871 (14) 和鈉）和驗土金屬陽離子（例如釣和鎂）、銨或水溶性胺加成 鹽（例如N-甲基還原葡糖胺（glue amine)-(me glum ίη e))、及 低級烷醇銨和其他藥學上可接受之有機胺的鹼鹽之藥學上 可接受之陽離子所形成者。 本文中“藥學上可接受之鹽”乙辭，除非特別指明，包 含可存在於本發明之化合物中之酸性或鹼性基團的鹽。在 性質上爲鹼性之本發明的化合物可與多種無機酸和有機酸 形成許多種鹽類。可用於製備上述鹼性化合物之藥學上可 接受之酸加成鹽的酸是可形成無毒性酸加成鹽者，即含有 藥學上可接受之陰離子的鹽，例如鹽酸鹽、氫溴酸鹽、氫 碘酸鹽、硝酸鹽、硫酸鹽、硫酸氫鹽、磷酸鹽、酸式磷酸 鹽、異菸酸鹽、乙酸鹽、乳酸鹽、水楊酸鹽、檸檬酸鹽、 酸式檸檬酸鹽、酒石酸鹽、泛酸鹽、酒石酸氫鹽、抗壞血 酸鹽、琥珀酸鹽、順丁烯二酸鹽、龍膽酸鹽、反丁烯二酸 鹽、葡糖酸鹽、葡糖醛酸鹽、糖二酸鹽、甲酸鹽、苯甲酸 鹽、榖胺酸鹽、甲磺酸鹽、乙磺酸鹽、苯磺酸鹽、對甲苯 磺酸鹽和pamoate [即1,1’-伸甲基-雙（2_羥基-3-萘甲酸鹽 )]。除了上述的酸以外，含有鹼性基團（例如胺基）之本發 明的化合物可與多種胺基酸形成藥學上可接受之鹽。 本發明亦涵蓋含有式1所示之化合物的前驅藥物之藥 學組成物。具有自由的胺基、醯胺基、羥基或羧基之式1 所示之化合物可轉換成前驅藥物。前驅藥物包含其中的胺 基酸基團，或由二或多個（例如二、三或四個）胺基酸基團 所形成的多肽鏈，經由肽鏈共價鍵結至式1所示之化合物 •17- 200539871 (15) 的自由的胺基、羥基或羧基之化合物。胺基酸基團包含（ 但不限於）20個天然生成的胺基酸（一般係以3個字母符號 表示），亦包含4-羥基脯胺酸、羥基賴胺酸、鎖鏈素 (desmosine)、異鎖鏈素（isodesmosine)、3 -經基組胺酸、 正纈胺酸、P-丙胺酸、γ-胺基丁酸、瓜胺酸、高半胱胺酸 、高絲胺酸、鳥胺酸和甲硫胺酸硯。前驅藥物亦包含其中 碳酸酯、胺基甲酸酯、醯胺和烷酯經由羰基碳前驅藥物側 鏈共價鍵結至上述式1的取代基之化合物。 本發明亦包含帶有保護基之式1所示之化合物。熟悉 此項技術人士將了解本發明之化合物亦可製成帶有某些利 於純化或貯存且在投服於患者之前可被去除之保護基。官 能基的保護和去保護揭示於“Protective Groups in Organic Chemistry'edited by J.W.F.McOmie, Plenum Pi’ess(1973)和 “Protective Groups in Organic Synthesis ”， 3rd edition,T.W. Greene and P.G.M. Wuts,Wiley~Interscience(1999) o 本發明之化合物包含式1所示之化合物之所有立體異 構物（例如順式和反式異構物）及所有的光學異構物（例如R 和S鏡像異構物），以及該異構物之外消旋混合物、非鏡像 異構混合物和其他混合物。 本發明之化合物、鹽和前驅藥物可以數種互變異構形 式存在，包含烯醇和亞胺形式，及酮和烯胺形式，及幾何 異構物，及其混合物。所有所述之互變異構物均涵蓋在本 發明的範圔內^互變異構物係以互變異構組的混合物存在 -18- 200539871 (16) 於溶液中。固態形式時，通常是其中一種互變異構物佔優 勢。即使只揭示一種互變異構物，本發明包含本發明之化 合物之所有的互變異構物。 本發明亦涵蓋本發明之阻轉異構物（atropisomer)。阻 轉異構物意指可分離成旋轉受阻的異構物之式1所示之化 合物。 本發明之化合物可含有烯類雙鍵。當此類鍵結存在時 ’本發明之化合物可以順式和反式構型及其混合物之形式 存在。 ‘‘適合的取代基”表示化學和藥學上可接受之官能基， 即不會使本發明之化合物的生物活性無效之基團。所述之 適合的取代基可由熟悉此項技術人士例行性地選擇。適合 的取代基之例子包含（但不限於）鹵基、全氟烷基、全氟烷 氧基、烷基、烯基、炔基、羥基、酮基、疏基、烷硫基、 院氧基、芳基或雜芳基、芳氧基或雜芳氧基、芳烷基或雜 芳烷基、芳烷氧基或雜芳烷氧基、H0-(C = 0)-基、胺基、 烷基-和二烷基胺基、胺甲醯基、烷羰基、烷氧羰基、烷 胺羰基、二烷胺羰基、芳羰基、芳氧羰基、烷磺醯基、芳 磺醯基等。熟悉此項技術人士均會了解許多取代基可爲其 他的取代基所取代。適合的取代基之其他例子包含式i所 不之化合物的定義中所例示者，包含上文所述之R1至Rl2 0 “爲…所中斷”意指其中的環碳原子被選自-(c = 0)、 - S02、- s-、-〇-、-N-、-NH -和-NR12 之單元所取代。例 -19- 200539871 (17)R5 and R6 are each selected from hydrogen,-(CrC6) alkyl,-(〇3-(: 7) cycloalkyl,-(C2-C9) heterocyclyl,-(C6_C1 ()) aryl,- (Ci-c9) heteroaryl, -COR12, and -S02R12 substituents; wherein the-(C ^ CeH end group,-(C3_C7) cyclocytyl group,-(C2-C9) hetero) of the R5 and R6 substituents Cyclic group,-(〇6- 一 C.) aryl,-(CrC9) heteroaryl, -COR ", and -s〇2Rl2 are optionally selected from hydrogen, halogen, -CF3,- CN,-(CrCe) courtyard, -NmCi-Cj alkyl, -NH (C3-C7) cycloalkyl, -NH (c2-C9) heterocyclyl, -NH (C6-C1 ()) aryl, -NmC ^ Cj heteroaryl, -NUCrCj courtyard), -N ((C3-C7) ring courtyard), -N ((C2_C9) heterocyclyl) 2, -n ((c6-ci0) aryl ) 2, -NUC ^ C9) heteroaryl) 2, -0 (c-c6) alkyl, -o (c3-c7) cycloalkyl, -o (c2-c9) heterocyclyl, -〇 (c6 — Ci.) Aryl, -CO2R7, -SO2NR5R6, -NR12S02R7, -s02R7, -coNH2, -CONHR7, and -CONR7R8; R7 and R8 may form together with the nitrogen atom which is linked-(C2-C9) Heterocyclyl R5 and R6 may form together with the linked atom-(C2-C9 ) Heterocyclyl, wherein the-(CfC: 9) heterocyclyl is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CF3, -N02, -CN,-(Ci -Ce) Alkyl mono (cv--13-200539871 (11), mono (c2-C6) alkynyl, mono-C = N_OH, mono-C ^ N-QUC ^ -Ce), -NR7R8,- OR12,-(C "C7) cycloalkyl,-(C2-C9) heterocyclyl, -CO2R12, -CONR7R8, -CONR5R8, -SR7, -SOR7, -S02R7, -S02NR7R8,- NHCOR12, -NR12CONR7R8, and -NR12S02R7 are substituted, wherein the-(C2-C9) heterocyclyl_ (C2_C6) alkenyl and-(C2_C6) alkynyl can be optionally passed through one to three R7 groups Substitution, and the-(C2-C9) heterocyclyl is optionally 1 to 3 selected from-(00), -S02, -S-, -0-®, -N-, -NH-, and -NR12 The unit is interrupted; R7 is selected from the group consisting of-(Ci-Ce) fluorenyl,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl,-(c6-c1 ()) aryl, and- (CrCd heteroaryl substituent: wherein-(c) -c6) alkyl,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl,-(C6-C1 ()) Aryl, and-(CrCOheteroaryl are optionally selected from hydrogen, halogen, hydroxyl, -CN,-(Ci-Cj Group, _NR122, and mono (Ci_c6) alkyl group; I R8 is selected from hydrogen,-(C ^ CJ alkyl,-(c3-c7) cycloalkyl,-(c2-c9) hetero Substituents of cyclic group,-(C6-C1 ()) aryl group, and-(Cl-C9) heteroaryl group; wherein-(C 丨 -C6) alkyl,-(C3-C7) of the R8 substituent Cycloalkyl, mono (C2-C9) heterocyclyl,-(CVc) D) aryl, and-(c factory c9) heteroaryl are optionally selected from hydrogen, halogen, hydroxyl,- CN,-((:〗-(: 6) alkyl ... NH2, -NHR9, -NR92, -0R9, _ (C3-C7) cycloalkyl, mono (C2-C9) heterocyclyl, -C〇2R1 . , _C〇NH2 ... c〇NHR ", and-CONR ^ R11 are substituted; wherein R1 in _c〇NR10Rll. And R11 can be linked to a nitrogen atom to form a _ (C2-C9) heterocyclic group; R9 and R " are each-(Ci-C6) alkyl; -14- 200539871 (12) R11 is hydrogen or _ (c-C6) alkyl; and R12 is selected from hydrogen,-(CrC6) alkyl,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl- (C6_C1 ()) aryl, And-(Crc9) heteroaryl substituents; wherein the R12 substituent is -d-Cd alkyl,-(c3_c7) cycloalkyl,-(c2-c9) heterocyclyl,-(C6-C1 () ) Aryl, and-(CrCj heteroaryl are optionally selected from 1 to 3, respectively, selected from hydrogen, halogen, -CF3, -CN, _ ((: plant (: 6), phenyl, -NhHC ^ -Ce) alkane -NH (C3-C7) cycloalkyl, -NH (C2-C9) ® heterocyclyl, -NH (C6-C1 ()) aryl, -NH (C6-C9) heteroaryl, -N (( Cr c6) alkyl) 2, -n ((c3-c7) cycloalkyl) 2, -n ((c2-c9) heterocyclyl) 2, -N ((c6-C10) aryl) 2,- NUC ^ Cg) heteroaryl) 2, -◦ (CrCe) alkyl, -0 (C3-C7) cycloalkyl, -〇 (C2-C9) heterocyclyl, -〇 (C6-C1 ()) aromatic Group, " " 〇 (C 「C9) heterospheric group,-(C3-C7) ring courtyard group,-(C2-C9) heterocyclic group, -C02R7, -CONH2, -CONHR7, and -CONR7R8 By the group; where R7 in _CONR7R8 R8 may, together with linked atoms, form _ (C2_C9) heterocyclyl. The present invention also includes isotopically-labeled compounds, which are the same as those shown in Formula 1, except that one or more of the atoms are Substituted by atoms of different atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as 2H, 3H, and 13C, respectively. ,] 4C, 15N, 180, 170, 31P, 32P, 35S, 18F, and 36C1. The compound of the present invention containing the above-mentioned isotope and / or other isotope of other atom, its precursor, and the pharmacy of the compound or the precursor All acceptable salts are within the scope of the present invention. Some isotopically-labeled compounds of the present invention (such as compounds containing radioactive isotopes of 15-15,200539871 (13), such as 3H and 14 C) may be used in medicine and / or Analysis of the distribution of the host tissue. Tritiated isotopes (ie 3H) and carbon-14 isotopes (ie 14 C) are particularly suitable due to their ease of preparation and easy detection. In addition, heavier isotopes (eg , I.e., 2H) substituents having from greater metabolic stability due thus may provide certain advantages (e.g., longer half-life in vivo or lower dosage requirements) on the treatment, and thus more appropriate in certain cases. The isotope-labeled compound and its precursor shown in Formula 1 of the present invention are usually prepared by the steps disclosed in the following reaction diagrams and / or examples and preparation examples, but non-labelled agents that are immediately available instead of non- Isotopic labeling agent. The present invention also relates to a pharmaceutically acceptable acid addition salt of the compound represented by Formula 1. The acids which can be used to prepare the pharmaceutically acceptable acid addition salts of the above-mentioned ageing compounds of the present invention are those which can form non-toxic acid addition salts, that is, salts containing pharmaceutically acceptable anions, such as hydrochloride, hydrogen Bromate, hydroiodate, nitrate, sulfate, bisulfate, phosphate, acid phosphate b salt, acetate, lactate, citrate, acid citrate, tartrate, tartrate , Succinate, maleate, fumarate, gluconate, gluconate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, Tosylate and pamoate [ie 1,1'-methylene-bis (2-hydroxy-3-naphthoate)]. The present invention also relates to a base addition salt represented by Formula 1. The chemical base which can be used as a reagent for preparing a pharmaceutically acceptable base salt of the compound represented by Formula 1 which is acidic in nature is one which can form a non-toxic base salt with the compound. The non-toxic alkali salts include (but are not limited to) additions of, for example, alkali metal cations (such as potassium-16-200539871 (14) and sodium) and earth metal cations (such as fishing and magnesium), ammonium, or water-soluble amines. Formed by pharmaceutically acceptable cations of salts (such as N-methyl reduced amine- (me glum ίη e)), and base salts of lower alkanolammonium and other pharmaceutically acceptable organic amines By. As used herein, the phrase "pharmaceutically acceptable salts", unless specifically stated, includes salts of acidic or basic groups that may be present in the compounds of the invention. The compounds of the present invention which are basic in nature can form many salts with various inorganic and organic acids. Acids which can be used to prepare the pharmaceutically acceptable acid addition salts of the above-mentioned basic compounds are those which can form non-toxic acid addition salts, that is, salts containing pharmaceutically acceptable anions, such as hydrochloride, hydrobromide , Hydroiodate, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, Tartrate, pantothenate, tartrate, ascorbate, succinate, maleate, gentisate, fumarate, gluconate, glucuronide, sugar di Acid salt, formate salt, benzoate salt, ammonium salt, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [ie 1,1'-methylene- Bis (2-hydroxy-3-naphthoate)]]. In addition to the aforementioned acids, the compounds of the present invention containing a basic group (e.g., an amino group) can form pharmaceutically acceptable salts with a variety of amino acids. The present invention also includes a pharmaceutical composition containing a prodrug of a compound represented by Formula 1. The compound represented by Formula 1 having a free amine, amido, hydroxyl or carboxyl group can be converted into a prodrug. The prodrug contains an amino acid group therein, or a polypeptide chain formed by two or more (for example, two, three, or four) amino acid groups, and is covalently bonded to the one shown in Formula 1 via a peptide chain. Compound 17-200539871 (15) A free amine, hydroxyl or carboxyl compound. Amino acid groups include (but are not limited to) 20 naturally occurring amino acids (usually represented by 3 letter symbols), and also include 4-hydroxyproline, hydroxylysine, desmosine, Isodesmosine, 3-histamine, n-valine, P-alanine, γ-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and Methionine hydrazone. Prodrugs also include compounds in which carbonates, carbamates, amidoamines, and alkyl esters are covalently bonded to the substituents of Formula 1 above via a carbonyl carbon prodrug side chain. The present invention also includes a compound represented by Formula 1 having a protecting group. Those skilled in the art will appreciate that the compounds of the present invention can also be made with protective groups that are useful for purification or storage and can be removed before administration to a patient. The protection and deprotection of functional groups is disclosed in "Protective Groups in Organic Chemistry 'edited by JWFMcOmie, Plenum Pi'ess (1973) and" Protective Groups in Organic Synthesis ", 3rd edition, TW Greene and PGM Wuts, Wiley ~ Interscience ( 1999) o The compounds of the present invention include all stereoisomers (such as cis and trans isomers) and all optical isomers (such as R and S mirror image isomers) of the compound represented by Formula 1, and The isomers are racemic mixtures, non-mirromeric mixtures and other mixtures. The compounds, salts and prodrugs of the present invention can exist in several tautomeric forms, including enol and imine forms, and keto and enamine forms , And geometric isomers, and mixtures thereof. All the tautomers are included within the scope of the present invention ^ Tautomers exist as mixtures of tautomeric groups -18- 200539871 (16) in In solution. In solid form, it is usually one of the tautomers that predominates. Even if only one tautomer is disclosed, the present invention includes all of the tautomers of the compounds of the present invention. Isomers. The present invention also encompasses atropisomers of the present invention. Atropisomers refer to compounds of formula 1 that can be separated into rotationally hindered isomers. The compounds of the present invention may contain Ethylene double bonds. When such a bond exists, the 'compounds of the present invention may exist in the cis and trans configurations and mixtures thereof. "Suitable substituents" means chemically and pharmaceutically acceptable functional groups, That is, a group which does not invalidate the biological activity of the compound of the present invention. Suitable substituents described can be routinely selected by those skilled in the art. Examples of suitable substituents include, but are not limited to, halo, perfluoroalkyl, perfluoroalkoxy, alkyl, alkenyl, alkynyl, hydroxy, keto, thio, alkylthio, and oxy , Aryl or heteroaryl, aryloxy or heteroaryloxy, aralkyl or heteroaralkyl, aralkoxy or heteroaralkoxy, H0- (C = 0) -yl, amine, Alkyl- and dialkylamino, carbamoyl, alkylcarbonyl, alkoxycarbonyl, alkylaminecarbonyl, dialkylaminecarbonyl, arylcarbonyl, aryloxycarbonyl, alkylsulfonyl, arylsulfonyl and the like. Those skilled in the art will understand that many substituents can be substituted for other substituents. Other examples of suitable substituents include those exemplified in the definition of compounds not represented by formula i, including R1 to R12 0 described above "is interrupted" means that the ring carbon atom therein is selected from-(c = 0), -S02, -s-, -〇-, -N-, -NH-, and -NR12. Example -19- 200539871 (17)

當取代基爲_(c6-c1())芳基，例如 則該環可被氮雜原子所中斷或取代而形成下式所示之When the substituent is _ (c6-c1 ()) aryl, for example, the ring may be interrupted or substituted by a nitrogen heteroatom to form the following formula

vU 使得環碳原子被雜原子氮所取代。本發明之化合物可 容許有至多3個此種取代或中斷。 本文中，“烷基”，以及文中提及之其他基團（例如烷 氧基）中之烷基，可爲直鏈或支鏈（例如甲基、乙基、正丙 基、異丙基、正丁基、異丁基、第二丁基、第三丁基）； 任意地經1至3個如上所定義之適合的取代基（例如氟、氯 、三氟甲基、（C^-C：6)烷氧基、（C6-C!。）芳氧基、三氟甲氧 基、二氟甲氧基或（C】-C6)院基）所取代。文中之“各個該院 基”意指在院氧基、嫌基或院胺基範圍內之任何前述的院 基。較佳的烷基包含（C^-Ce)烷基，更宜是（C^-C,)烷基， 最宜是甲基和乙基。 本文中，“環烷基”乙辭意指單、雙或三環碳環（例如 環丙基、環丁基、環戊基、環己基、環庚基、環辛基、環 壬基、環戊烯基、環己烯基、雙環[2.2.1]庚烷基、雙環 [3.2.1]辛院基、和雙環[5.2.0]壬院基等）；任意地含有1或 2個雙鍵及任意地經1至3個如上所定義之適合的取代基（例 -20- 200539871 (18) 如氟、氯、三氟甲基、（CrCj烷氧基、（c6-c1())芳氧基、 三氟甲氧基、二氟甲氧基或（CrCj烷基）所取代。 本文中，“鹵素”乙辭包含氟、氯、溴、或碘、或氟離 子、氯離子、溴離子、或碘離子。 本文中，“烯基”乙辭意指含有2至6個碳原子之直鏈或 支鏈未飽和基團，包含（但不限於）乙烯基、1-丙烯基、2-丙烯基（烯丙基）、異丙烯基、2-甲基-1-丙烯基、1_ 丁烯 基、2-丁烯基等；任意地經1至3個如上所定義之適合的取 代基（例如氟、氯、三氟甲基、（Ci-Cj烷氧基、（C6_C10) 芳氧基、三氟甲氧基、二氟甲氧基或烷基）所取代 〇 本文中，“炔基”乙辭意指帶有一個參鍵之直鏈或支鏈 烴基，包含（但不限於）乙炔基、丙炔基、丁炔基等；任意 地經1至3個如上所定義之適合的取代基（例如氟、氯、三 氟甲基、（C^CJ烷氧基、（C6-C1())芳氧基、三氟甲氧基、 二氟甲氧基或（C^Ce)烷基）所取代。 本文中，“羰基”或“（C = 0)”（當以括號表示時爲烷羰基 、烷基_(〇0)-或烷氧羰基）乙辭意指〉C = 0基團中與第二 個基團（例如烷基或胺基（即醯胺基））相連結的部份。烷氧 羰胺基（即烷氧基（C = 0)_NH_)意指胺基甲酸烷酯基。本文 中，羰基之定義亦相等於（C = 0)。烷羰胺基意指例如乙醯 胺之基團。 本文中，“芳基”乙辭意指芳族基團，例如苯基、萘基 、四氫萘基、茚滿基等；任意地經1至3個如上所定義之適 -21 - 200539871 (19) 合的取代基所取代。 本文中，“雜芳基”乙辭意指通常環中帶有一個選自〇 、5和？^的雜原子之芳族雜環基。除了上述的雜原子之外 ，芳族基團的環中可任意地帶有至多4個N原子。例如， 雜芳基包含吡啶基、吡嗪基、嘧啶基、噻吩基、呋喃基、 咪唑基、吡咯基、噁唑基（例如1,3_噁唑基、1，2_噁唑基） 、噻唑基（例如1,2-噻唑基、1,3-噻唑基）、吡唑基、四唑 ® 基、三唑基（例如1,2,3-三唑基、1,2,4-三唑基）、噁二唑 基（例如1,2,3-噁二唑基）、噻二唑基（例如1,3,4-噻二唑基） 、喃啉基、異喹啉基、苯並噻吩基、苯並呋喃基、吲哚基 等；任意地經1至3個如上所定義之適合的取代基（例如氟 、氯、三氟甲基、（C^Cj烷氧基、（C6-C1())芳氧基、三氟 甲氧基、二氟甲氧基或（CrCd烷基）所取代。 本文中，“雜環基”乙辭意指含有1至9個碳原子和1至4 個選自N、0、S(0)nSNR的雜原子之環狀基團。此類環的 &例子包含氮雜環丁烷基、四氫呋喃基、咪唑烷基、吡咯烷 基、哌啶基、哌嗪基、噁唑烷基、噻唑烷基、吡唑烷基、 硫代嗎啉基、四氫噻嗪基、四氫噻二嗪基、嗎啉基、氧雜 環丁烷基、四氫二嗪基、噁嗪基、噁噻嗪基、吲哚啉基、 異吲哚啉基、奎寧環基、色滿基、異色滿基、苯並噁嗪基 等。該單環飽和或部份飽和環系統的例子是四氫呋喃-2-基、四氫呋喃-3-基、咪唑烷-1-基、咪唑烷-2-基、咪唑 烷_4_基、吡咯烷-卜基、吡咯烷-2-基、吡咯烷-3-基、哌 U定-1-基、峨陡-2 -基、哌Π定-3-基、呢η秦-1-基、呢嗪_2- -22- 200539871 (20) 基、哌嗪-3-基、1,3-噁唑烷-3-基、異噻唑烷基、1，3-異 噻唑烷-3-基、1,2-吡唑烷-2-基、1,3-吡唑烷-1-基、硫 代嗎啉-基、1，2_四氫噻嗪-2-基、1,3-四氫噻嗪-3-基、 四氫噻二嗪-基、嗎啉-基、1，2-四氫二嗪-2-基、1,3-四 氫二嗪-1-基、1,4-噁嗪-2-基、1,2,5-噁噻嗪-4-基等； 任意地含有1或2個雙鍵及任意地經1至3個如上所定義之適 合的取代基（例如氟、氯、三氟甲基、（〇广(：6)烷氧基、 (C6-C1())芳氧基、三氟甲氧基、二氟甲氧基或（CrCj烷基 )所取代。 本文中，氮雜原子意指N=、>N和NH-;其中-N =意指 氮雙鍵；〉N意指含有二個鍵連結的氮；而-N意指含有一 個鍵的氮。 本文中，“體系”乙辭意指分成不連結的亞屬之化合物 或用途的特殊群集。此類亞屬的判別可根據一特定取代基 (例如特定的R1或R3基團）。而其他的亞屬的判別係根據多 種取代基的組合（例如其中R2是氫且R1是（C^-C6)烷基之所 有的化合物）。 因此，本發明提供一種式1所示之化合物，其中R3是 氫。 本發明亦提供一種式1所示之化合物，其中R3是選自 -（C6-C1Q)芳基或-(C^CJ雜芳基，而其任意地經1至3個分 別選自鹵素、羥基、-（CrC6)烷基、烷基 -p(o)(o(c!-c6)院基）2、-(c3-C1())環垸基、-(c6-c1())芳基 、-(C2-C9)雜環基、-(CrC9)雜芳基、-nr5r6、 -23- 200539871 (21) -NHS〇2(CrC6)烷基、-NHS〇2(C3-C6)環烷基、-NUC〗-C6) 烷基）（S〇2(C「C6)烷基）、-N((C「C6)烷基）（S02(C「C6)環烷 基）、-N((C3-C6)環烷基 HSOjCVCe)烷基）、-1^(((：3-€：6)環 烷基）（S〇2(C3-C6)環烷基）、-CKC^Ce)烷基、-0_S02(C】-c6)烷基、so2(c3-c6)環烷基、-(COMCrCj烷基、 一（C〇）CF3、一（C〇）（C3-Ci〇)環院基、一（CO)(C6-C10)芳基、 -（CO)(C2-C9)雜環基、-（COMCrCj 雜芳基、-(co)o(c】-C6)烷基、-(co)o(c3-C,。）環烷基、-(co)o(c6-c1())芳基 、-（C0)0(C2-C9)雜環基、-(CCOcKCi-Cg)雜芳基、 -（COKCrCe)烷基-CKCrCe)烷基-、-S02(c厂C6)烷基、 -S〇2(C3_C6)環烷基、-S02CF3、-S02NH2、-S02NH(CrC6) 烷基、-S02NH(C3-C6)環烷基、-SC^NUCrCd 烷基）2、 -5〇21^(((：1-0：6)烷基）（（0：3-(：6)環烷基）、-5〇:^(((：3-(：6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-(C6-Cl。）芳基 或-雜方基任意地爲1至3個選自-S-、-〇-、_N-、 - NH-和-NR12之單元所中斷。 本發明之另一體系是一種式1所示之化合物，其中R3 是選自-(C3_C1())環院基、-(c2-c9)雜環基、和- (Ci-Ce)院 基-(C2-C9)雜環基，而其任意地經1至3個分別選自鹵素、 羥基、-（(：，-(：6)烷基、-(CrCj 烷基-PiOKcKCrCe)烷基）2 、-（C3_C1())環院基、-(C6-C1Q)芳基、-(c2-C9)雜環基、 -(CrC9)雜芳基、-NR5R6、-NHSCMCrCj烷基、 -NHS02(C3-C6)環烷基、-N((CrC6)烷基 MSOjCi-Ce)烷基） 、-N((C广C6)烷基）（S02(C3 - C6)環烷基）、-N((C3 - C6)環烷 -24 - 200539871 (22) 基 MSOjCi-Ce)烷基）、-N((C3-C6)環烷基）（S02(C3_C6)環烷 基）、-烷基、-O-SOjCrCe)烷基、-〇-S〇2(C3 -C6)環烷基、-(COMC^CJ烷基、-（CO)CF3、-(CO)(C3-C1())環烷基、-(co)(c6-c1())芳基、-(co)(c2-c9)雜環基 、-（C〇）（C「C9)雜芳基、-（C0)0(CrC6)烷基、 -（co)o(c3-c1())環烷基、-(co)o(c6-c1())芳基、 -（co)o(c2-C9)雜環基、-(C0)0(CrC9)雜芳基、 -（CO)(C 丨-c6)烷基烷基-、-SO^C^-Ce)烷基、 -S02(C3-C6)環院基、-S02CF3、-S02NH2、-S〇2NH(C!_C6) 烷基、-S02NH(C3-C6)環烷基、-SC^NUCrCe)烷基）2、 - so2n((c「c6)院基）（（c3-c6)環烷基）、-s〇2N((C3-C6)環烷 基）2、和-so2nr5r6之基團所取代，其中該—（C3-Ci。）環烷 基、_(c2-c9)雜環基、和-(c]-c6)烷基-(c2-c9)雜環基任 意地爲 1至 3個選自-（C = 0)、-S02、-S-、-N-、 - NH-和-NR12之單元所中斷。 本發明之另一體系是一種式1所示之化合物，其中R3 是-（<^-(：6)烷基，而其任意地經1至3個分別選自鹵素、羥 基、-（CrCj 烷基、-(CrCd 烷基—p(〇)(〇(Ci-c6)烷基）2 、-(C3-C,。）環烷基、-（C6-C1D)芳基、-(c2-C9)雜環基、 -（C^CJ雜芳基、-NR5R6、-NHS〇2(Cl-c6)烷基、 -nhso2(c3-C6)環烷基、-NUC!-c6)院基）（so2(c「c6)院基） 、-N((C「C6)烷基）（S02(C3-C6)環烷基）、-N((c「c6)環烷 基 HSOJC】-C6)烷基）、-N((c3-c6)環烷基）（s〇2(C3-C6)環烷 基）、-Od-Ce)烷基、-O-SOJe!-c6)烷基、-0-S02(C3- -25- 200539871 (23) C6)環烷基、-(C〇）（C「C6)烷基、-（CO)CF3、-（CO)(C3 -C10)環烷基、-(C〇）（C「C10)芳基、_(CO)(C2-C9)雜環基 、-（C〇）（CrC9)雜芳基、-（(:⑴以…^^^烷基、 -（co)〇（c3-c1C))環烷基、-（co)o(c6-c1())芳基、 -(co)o(c2-c9)雜環基、-(CCOCMC^-Cd雜芳基、 -（(：0)((：「C6)烷基-CKCrCe)烷基-、-SOjCi-Cj 烷基、 -S02(C3-C6)環烷基、-S02CF3、-S02NH2、-SC^NHiCrCe) •烷基、-so2NH(c3-c6)環烷基、一 s〇2N((Cl-C6)烷基）2、 - SC^NUCi-C6)烷基）（（C3-C6)環烷基）、-S〇2N((C3_c6)環烷 基）2、和-S〇2NR5R6之基團所取代，其中該_(Ci-c6)烷基任 意地爲 1至 3個選自-(C = 0)、-s〇2、 - NH-和-NR12之單元所中斷。 此外，本發明提供一種式2所示之化合物： ΗvU causes the ring carbon atom to be replaced by a heteroatom nitrogen. The compounds of the invention may tolerate up to three such substitutions or interruptions. As used herein, "alkyl", as well as alkyl groups in other groups mentioned herein (such as alkoxy), may be straight or branched (such as methyl, ethyl, n-propyl, isopropyl, N-butyl, isobutyl, second butyl, third butyl); optionally via 1 to 3 suitable substituents as defined above (eg fluorine, chlorine, trifluoromethyl, (C ^ -C : 6) substituted with alkoxy, (C6-C !.) aryloxy, trifluoromethoxy, difluoromethoxy or (C) -C6). "Each of the said radicals" in the text means any of the aforementioned radicals within the scope of the radicals, radicals or amino radicals. Preferred alkyl groups include (C ^ -Ce) alkyl, more preferably (C ^ -C,) alkyl, most preferably methyl and ethyl. As used herein, the term "cycloalkyl" means a mono-, bi- or tricyclic carbocyclic ring (eg, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, ring Pentenyl, cyclohexenyl, bicyclo [2.2.1] heptyl, bicyclo [3.2.1] octyl, and bicyclo [5.2.0] nonyl, etc.); arbitrarily contains 1 or 2 bis Bond and optionally through 1 to 3 suitable substituents as defined above (Example -20- 200539871 (18) such as fluorine, chlorine, trifluoromethyl, (CrCj alkoxy, (c6-c1 ()) aromatic Oxy, trifluoromethoxy, difluoromethoxy or (CrCj alkyl). In this context, the term "halogen" includes fluorine, chlorine, bromine, or iodine, or fluoride, chloride, or bromide. Or an iodide ion. In this context, "alkenyl" means a straight or branched unsaturated group containing 2 to 6 carbon atoms, including (but not limited to) vinyl, 1-propenyl, 2- Propenyl (allyl), isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, etc .; optionally via 1 to 3 suitable substituents as defined above ( Such as fluorine, chlorine, trifluoromethyl, (Ci-Cj alkoxy , (C6_C10) aryloxy, trifluoromethoxy, difluoromethoxy or alkyl). In this context, "alkynyl" ethyl means a straight or branched chain hydrocarbon group with a para-bond, Contains (but is not limited to) ethynyl, propynyl, butynyl, etc .; optionally via 1 to 3 suitable substituents as defined above (eg, fluorine, chlorine, trifluoromethyl, (C ^ CJ alkoxy) (C6-C1 ()) aryloxy, trifluoromethoxy, difluoromethoxy or (C ^ Ce) alkyl). In this context, "carbonyl" or "(C = 0)" (Alkylcarbonyl, alkyl_ (〇0)-, or alkoxycarbonyl when expressed in parentheses) Ethyl means >> C = 0 and a second group (such as an alkyl or amine group (ie, 醯Amine group)). The alkoxycarbonylamino group (ie, alkoxy group (C = 0) _NH_) means alkyl carbamate group. In this article, the definition of carbonyl group is also equivalent to (C = 0) Alkylcarbonylamino means a group such as acetamido. Herein, the "aryl" ethyl means an aromatic group such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, etc .; optionally 1-3 as defined above-21-200539871 (19) Substituted by a substituted substituent. As used herein, the term "heteroaryl" means an aromatic heterocyclic group generally having a heteroatom selected from 0, 5 and? ^ In the ring. In addition to the atom, the aromatic group may optionally have up to 4 N atoms in the ring. For example, heteroaryl includes pyridyl, pyrazinyl, pyrimidinyl, thienyl, furyl, imidazolyl, pyrrolyl, oxa Oxazolyl (e.g. 1,3-oxazolyl, 1,2_oxazolyl), thiazolyl (e.g. 1,2-thiazolyl, 1,3-thiazolyl), pyrazolyl, tetrazole®, triazole Oxazolyl (e.g. 1,2,3-triazolyl, 1,2,4-triazolyl), oxadiazolyl (such as 1,2,3-oxadiazolyl), thiadiazolyl (such as 1 , 3,4-thiadiazolyl), arolinyl, isoquinolinyl, benzothienyl, benzofuranyl, indolyl, etc .; optionally via 1 to 3 suitable substituents as defined above (Such as fluorine, chlorine, trifluoromethyl, (C ^ Cj alkoxy, (C6-C1 ()) aryloxy, trifluoromethoxy, difluoromethoxy or (CrCd alkyl)). As used herein, the term "heterocyclyl" means a cyclic group containing 1 to 9 carbon atoms and 1 to 4 heteroatoms selected from N, 0, S (0) nSNR. Examples of such rings include azetidinyl, tetrahydrofuranyl, imidazolidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, thio Morpholinyl, tetrahydrothiazinyl, tetrahydrothiadiazinyl, morpholinyl, oxetanyl, tetrahydrodiazinyl, oxazinyl, oxathiazinyl, indololinyl, isoindole Indolinyl, quinuclidinyl, chromanyl, heterochromanyl, benzoxazinyl and the like. Examples of such monocyclic saturated or partially saturated ring systems are tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyrrolidine-bu Base, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-1-yl, azedol-2-yl, piperidin-3-yl, n-qin-1-yl, morphazine_ 2- -22- 200539871 (20) group, piperazin-3-yl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-isothiazolidin-3-yl, 1,2 -Pyrazolidine-2-yl, 1,3-pyrazolidine-1-yl, thiomorpholin-yl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazine- 3-yl, tetrahydrothiadiazine-yl, morpholin-yl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, 1,4-oxazine- 2-yl, 1,2,5-oxathiazin-4-yl, etc .; optionally containing 1 or 2 double bonds and optionally 1 to 3 suitable substituents as defined above (e.g. fluorine, chlorine, Trifluoromethyl, (β- (6) alkoxy, (C6-C1 ()) aryloxy, trifluoromethoxy, difluoromethoxy, or (CrCj alkyl). A nitrogen heteroatom means N =, > N and NH-; where -N = means a nitrogen double bond;> N means a nitrogen containing two bonds; and -N Means a nitrogen containing a bond. In this context, the term "system" means a special group of compounds or uses divided into unconnected subgenera. The discrimination of such subgenera can be based on a specific substituent (such as a specific R1 or R3 group). The discrimination of other subgenus is based on a combination of various substituents (for example, all compounds in which R2 is hydrogen and R1 is (C ^ -C6) alkyl). Therefore, the present invention provides a formula 1 The compound shown, wherein R3 is hydrogen. The present invention also provides a compound represented by Formula 1, wherein R3 is selected from-(C6-C1Q) aryl or-(C ^ CJheteroaryl, and optionally 1 to 3 are selected from halogen, hydroxyl,-(CrC6) alkyl, alkyl-p (o) (o (c! -C6) yl),-(c3-C1 ()) cyclofluorenyl, -(c6-c1 ()) aryl,-(C2-C9) heterocyclyl,-(CrC9) heteroaryl, -nr5r6, -23- 200539871 (21) -NHS〇2 (CrC6) alkyl,- NHS〇2 (C3-C6) cycloalkyl, -NUC〗 -C6) alkyl) (S〇2 (C "C6) alkyl), -N ((C" C6) alkyl) (S02 (C " C6) cycloalkyl), -N ((C3-C6) cycloalkyl HSOjCVCe) alkyl), -1 ^ ((((: 3- €: 6) cycloalkyl)) (S〇2 (C3-C6) Cycloalkyl) , -CKC ^ Ce) alkyl, -0_S02 (C) -c6) alkyl, so2 (c3-c6) cycloalkyl,-(COMCrCjalkyl, mono (C〇) CF3, mono (C〇) (C3 -Ci〇) Cyclocyclyl, mono (CO) (C6-C10) aryl,-(CO) (C2-C9) heterocyclyl,-(COMCrCj heteroaryl,-(co) o (c) -C6 ) Alkyl,-(co) o (c3-C ,. ) Cycloalkyl,-(co) o (c6-c1 ()) aryl,-(C0) 0 (C2-C9) heterocyclyl,-(CCOcKCi-Cg) heteroaryl,-(COKCrCe) alkyl -CKCrCe) alkyl-, -S02 (C plant C6) alkyl, -S〇2 (C3-C6) cycloalkyl, -S02CF3, -S02NH2, -S02NH (CrC6) alkyl, -S02NH (C3-C6) ring Alkyl, -SC ^ NUCrCd alkyl) 2, -5〇21 ^ (((: 1-0: 6) alkyl) ((0: 3-(: 6) cycloalkyl), -50: ^ (((: 3-(: 6) cycloalkyl) 2, and -so2nr5r6 are substituted, wherein the-(C6-Cl.) Aryl or -heterospheric group is optionally 1 to 3 selected from The units of -S-, -〇-, -N-, -NH- and -NR12 are interrupted. Another system of the present invention is a compound represented by Formula 1, wherein R3 is selected from-(C3_C1 ()). ,-(C2-c9) heterocyclyl, and-(Ci-Ce) yl- (C2-C9) heterocyclyl, which are optionally selected from halogen, hydroxy,-(( :,-(: 6) alkyl,-(CrCj alkyl-PiOKcKCrCe) alkyl) 2,-(C3_C1 ()) cycloalkyl,-(C6-C1Q) aryl,-(c2-C9) heterocycle ,-(CrC9) heteroaryl, -NR5R6, -NHSCMCrCj alkyl, -NHS02 (C3-C6) cycloalkyl, -N ((CrC6) alkylMSOjCi-Ce) alkyl), -N ((C C6) alkyl (S02 (C3-C6) cycloalkyl), -N ((C3-C6) cycloalkane-24-200539871 (22) yl MSOjCi-Ce) alkyl), -N ((C3-C6) cycloalkyl) (S02 (C3_C6) cycloalkyl), -alkyl, -O-SOjCrCe) alkyl, -0-S〇2 (C3-C6) cycloalkyl,-(COMC ^ CJ alkyl,-(CO) CF3 ,-(CO) (C3-C1 ()) cycloalkyl,-(co) (c6-c1 ()) aryl,-(co) (c2-c9) heterocyclyl,-(C〇) (C "C9) heteroaryl,-(C0) 0 (CrC6) alkyl,-(co) o (c3-c1 ()) cycloalkyl,-(co) o (c6-c1 ()) aryl,- (Co) o (c2-C9) heterocyclyl,-(C0) 0 (CrC9) heteroaryl,-(CO) (C 丨 -c6) alkylalkyl-, -SO ^ C ^ -Ce) alkane Group, -S02 (C3-C6) cyclosynthetic group, -S02CF3, -S02NH2, -S〇2NH (C! _C6) alkyl, -S02NH (C3-C6) cycloalkyl, -SC ^ NUCrCe) alkyl) 2,-so2n ((c "c6) courtyard group) ((c3-c6) cycloalkyl), -s02N ((C3-C6) cycloalkyl) 2, and -so2nr5r6 are substituted, where The-(C3-Ci. ) Cycloalkyl, _ (c2-c9) heterocyclyl, and-(c) -c6) alkyl- (c2-c9) heterocyclyl are optionally 1 to 3 selected from-(C = 0), -S02, -S-, -N-, -NH- and -NR12 are interrupted. Another system of the present invention is a compound represented by Formula 1, wherein R3 is-(< ^-(: 6) alkyl, and it is arbitrarily selected from 1 to 3 selected from halogen, hydroxyl,-(CrCj Alkyl,-(CrCd alkyl-p (〇) (〇 (Ci-c6) alkyl) 2,-(C3-C,.) Cycloalkyl,-(C6-C1D) aryl,-(c2- C9) heterocyclyl,-(C ^ CJ heteroaryl, -NR5R6, -NHS〇2 (Cl-c6) alkyl, -nhso2 (c3-C6) cycloalkyl, -NUC! -C6) radical) (So2 (c "c6) institution), -N ((C" C6) alkyl) (S02 (C3-C6) cycloalkyl), -N ((c "c6) cycloalkylHSOJC] -C6) Alkyl), -N ((c3-c6) cycloalkyl) (s〇2 (C3-C6) cycloalkyl), -Od-Ce) alkyl, -O-SOJe! -C6) alkyl,- 0-S02 (C3--25- 200539871 (23) C6) cycloalkyl,-(C〇) (C 「C6) alkyl,-(CO) CF3,-(CO) (C3-C10) cycloalkyl ,-(C〇) (C "C10) aryl,-(CO) (C2-C9) heterocyclyl,-(C〇) (CrC9) heteroaryl,-((: ⑴ 以 ... ^^^ alkane ,-(Co) 〇 (c3-c1C)) cycloalkyl,-(co) o (c6-c1 ()) aryl,-(co) o (c2-c9) heterocyclyl,-(CCOCMC ^ -Cd heteroaryl,-((: 0) ((: "C6) alkyl-CKCrCe) alkyl-, -SOjCi-Cj alkyl, -S02 (C 3-C6) cycloalkyl, -S02CF3, -S02NH2, -SC ^ NHiCrCe) • alkyl, -so2NH (c3-c6) cycloalkyl, monosodium ((Cl-C6) alkyl) 2,- SC ^ NUCi-C6) alkyl) ((C3-C6) cycloalkyl), -S〇2N ((C3_c6) cycloalkyl) 2, and -S〇2NR5R6 groups, where the _ (Ci -c6) alkyl is optionally interrupted by 1 to 3 units selected from-(C = 0), -s〇2, -NH-, and -NR12. In addition, the present invention provides a compound represented by Formula 2: Η

2 其中Α是選自下列基團： -26- 2005398712 where A is selected from the group: -26- 200539871

其中m是0至3之整數，及R13是選自氫、鹵素、羥基、 (CrC6)烷基、（C3-C7)環烷基、（C6-C1Q)芳基、（CrCd 雜 芳基、（C2-C9)雜環基、烷基、〇-(C3-C7)環烷基 、SC^-iCi-Ce)烷基、S02-(C3-C7)環烷基、NHSOJC,-C6) 烷基、NUC^Ce)烷基）（S02(C】-C6)烷基）、N((C3-C7)環烷 基 C6)烷基）、Ν(((^-(：6)烷基）（S02(C3-C7)環烷基） 、N((C3-C7)環烷基）（S02(C3-C7)環烷基）、〇5〇2((：1-0：6)烷 基、S〇2CF3 、 S〇2NH2、 SO^HiCj-Ce)^ Μ 、 S〇2NH(C3 -C7)環烷基、S〇2NR5R6、SC^NUCrCd 烷基）2、CF3、C〇- -27- 200539871 (25) (Ci-Ce)烷基、C〇-（C3_C7)環烷基、C〇CF3、C〇2(C】- C6)院Where m is an integer from 0 to 3, and R13 is selected from hydrogen, halogen, hydroxyl, (CrC6) alkyl, (C3-C7) cycloalkyl, (C6-C1Q) aryl, (CrCd heteroaryl, ( C2-C9) heterocyclyl, alkyl, 0- (C3-C7) cycloalkyl, SC ^ -iCi-Ce) alkyl, S02- (C3-C7) cycloalkyl, NHSOJC, -C6) alkyl , NUC ^ Ce) alkyl) (S02 (C) -C6) alkyl), N ((C3-C7) cycloalkylC6) alkyl), N (((^-(: 6) alkyl) ( S02 (C3-C7) cycloalkyl), N ((C3-C7) cycloalkyl) (S02 (C3-C7) cycloalkyl), 0502 ((: 1-0: 6) alkyl, S〇2CF3, S〇2NH2, SO ^ HiCj-Ce) ^ M, S〇2NH (C3-C7) cycloalkyl, S〇2NR5R6, SC ^ NUCrCd alkyl) 2, CF3, Co--27- 200539871 (25) (Ci-Ce) alkyl, Co- (C3-C7) cycloalkyl, CoCF3, Co2 (C) -C6)

和with

之取代基 〇 本發明之另一體系是一種如下式3所示之化合物：The substituent 〇 Another system of the present invention is a compound represented by the following formula 3:

3 其中B是選自下列基團：3 where B is selected from the group:

R4R4

ΛΛ

子(R13)mChild (R13) m

-28- 200539871 (26) 本發明亦提供一種如下式4所示之化合物：-28- 200539871 (26) The present invention also provides a compound represented by the following formula 4:

4 其中D是選自下列基團：4 where D is selected from the group:

-29 - 200539871-29-200539871

(27)(27)

其中q是1至2之整數。 本發明之另一體系是一種如下式5所示之化合物：Where q is an integer from 1 to 2. Another system of the present invention is a compound represented by the following formula 5:

5 -30- 200539871 (28) 其中E是選自下式所示之基團： 乂 / 、N’5 -30- 200539871 (28) where E is selected from the group consisting of: 乂 /, N ’

02 R14 其中R14是選自（CrCd烷基、（c3-c7)環烷基、和（C2-c9)雜環基，及R15是選自氫、（CrC6)烷基、（c3-c7)環烷基 、和（C2-C9)雜環基。 因此，本發明提供一種式1所示之化合物，其中R1是 選自氫、羥基、和-((:广C6)烷基，而其任意地經1至3個分 別選自氫、鹵素、經基、-CN、-（C^Ce)焼基、-NR5R6、 -OR12、-(C3-C7)環烷基、-（C2-C9)雜環基、一 C02R12、 -CONR5R6、和-C〇NR5R8之基團所取代。 本發明亦提供一種式1所示之化合物，其中R1是-(Cr Ce)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-(c「C6)烷基、-NR5R6、-〇R”、一（C「C7)環烷基 、-(C2-C9)雜環基、-C02R12、-CONR5R6、和-CONR5R8 之 基團所取代。 本發明亦提供一種式1所示之化合物，其中Ri是選自 -（C^C：7)環烷基和-(c2-C9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、-CN、-（(：「(：6)烷基、-NR5R6 、-〇R12、-（C3-C7)環烷基、-(c2-c9)雜環基、_c〇2R12、 -CONR5R6、和_c〇nr5r^基團所取代。 -31 - 200539871 (29) 本發明亦提供一種式1所示之化合物，其中R1是選自 一〇（Ci - C6)院基、-〇(c3-c7)環院基、和- 〇（c2-c9)雜環基 ，而其任意地經1至3個分別選自氫、鹵素、羥基、-CN 、一（K6)烷基、-NR5R6、-OR12、-(C3-C7)環烷基、 -(C2-C9)雜環基、-c〇2R12、-CONR5R6、和-CONR5R8 之基 團所取代。較佳體系中，R1是烷基，而其任意 地經1至3個分別選自氫、_素、翔基、-CN、院 ® 基、—NR5R6、-OR"、-(C3-c7)環烷基、—（c2-c9)雜環基 、-C02R12、一CONR5R6、和-CONR5R8之基團所取代。 本發明之一體系是一種式1所示之化合物，其中R1是 一NR5R6，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、烷基、-NR5R6、-〇R12、-(C3_C7)環烷基 、-（C2-C9)雜環基、-C02R12、-CONR5R6、和-CONR5R8 之 基團所取代。 本發明之另一體系是一種式1所示之化合物，其中R1 ^ 是選自-SR7、-SOR7、-S02R7、和- S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-cn、-(Ci_C6)烷基 、-NW、—〇Rl2、—（C3-c7)環烷基、_(C2-C9)雜環基、 -C02R12、-CONR5R6、和-CONR5R8之基團所取代。較佳體 系中，R1是- S02NR5R6，而其任意地經1至3個分別選自氫 、鹵素、羥基、-CN、-（CrCj 烷基、-NR5R6、- OR12、 一（C3 - C7)環烷基、-(c2-C9)雜環基、-C〇2R12、- CONR5R6 、和-CONR5R8之基團所取代。 本發明亦提供一種式1所示之化合物，其中R1是 -32 - 200539871 (30)02 R14 wherein R14 is selected from the group consisting of (CrCd alkyl, (c3-c7) cycloalkyl, and (C2-c9) heterocyclic groups, and R15 is selected from the group consisting of hydrogen, (CrC6) alkyl, and (c3-c7) ring Alkyl, and (C2-C9) heterocyclyl. Therefore, the present invention provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of hydrogen, hydroxyl, and-((: C6) alkyl, and optionally After 1 to 3 are selected from hydrogen, halogen, meridian, -CN,-(C ^ Ce) fluorenyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) hetero Substituted with a cyclic group, a C02R12, -CONR5R6, and -CONR5R8. The present invention also provides a compound represented by Formula 1, wherein R1 is-(Cr Ce) alkyl, and it is optionally 3 selected from hydrogen, halogen, hydroxyl, -CN,-(c "C6) alkyl, -NR5R6, -〇R", mono (C "C7) cycloalkyl,-(C2-C9) heterocyclyl , -C02R12, -CONR5R6, and -CONR5R8. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from-(C ^ C: 7) cycloalkyl and-(c2-C9 ) Heterocyclyl, which is optionally selected from hydrogen, halogen, hydroxyl, -CN,-((: "(: 6) alkyl, -NR5R6, -〇R12, -(C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -co2R12, -CONR5R6, and -coonr5r ^ groups. -31-200539871 (29) The present invention also provides a A compound represented by Formula 1, wherein R1 is selected from the group consisting of a 10 (Ci-C6) group, a -0 (c3-c7) ring group, and a-0 (c2-c9) heterocyclic group, and optionally 1 to 3 are selected from hydrogen, halogen, hydroxyl, -CN, mono (K6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl,- 〇2R12, -CONR5R6, and -CONR5R8 are substituted. In a preferred system, R1 is an alkyl group, which is arbitrarily selected from 1 to 3 selected from the group consisting of hydrogen, _ prime, Xiangji, -CN, and ® group, —NR5R6, -OR ",-(C3-c7) cycloalkyl,-(c2-c9) heterocyclyl, -C02R12, a CONR5R6, and -CONR5R8 group. One system of the present invention Is a compound represented by Formula 1, wherein R1 is NR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN, alkyl, -NR5R6, -〇R12,-(C3_C7) Cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 are substituted. Another body of the present invention Is a compound represented by Formula 1, wherein R1 ^ is selected from the group consisting of -SR7, -SOR7, -S02R7, and -S02NR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -cn,- (Ci_C6) alkyl, -NW, -OR12,-(C3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 are substituted. In a preferred system, R1 is -S02NR5R6, and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(CrCj alkyl, -NR5R6, -OR12, and one (C3-C7) ring Substituted with alkyl,-(c2-C9) heterocyclyl, -CO2R12, -CONR5R6, and -CONR5R8. The present invention also provides a compound represented by Formula 1, wherein R1 is -32-200539871 ( 30)

一 ΐυ2Κ 、—C〇NR5R6、一NHCOR】2、一NR12C〇NR5R6、或 -MK12S〇2R7，而其任意地經1至3個分別選自氫、_素、經 基、-CN、-（Ci-C6)烷基、一 nr5r6、_〇R"、一環烷 基、一（C2-C9)雜環基、一c〇2R12、_C〇NR5R6、禾口一c〇NR5R8 之基團所取代。較佳體系中，以是-NRl2s〇2R7，而其任意 地經1至3個分別選自氫、鹵素、羥基、—CN、—（C1_C6)烷 基、-NR5R6、_〇Rl2、-(C3 —C7)環烷基、-(C2 —雜環基 、-C02R12、-CONR5R6、和一 c〇NR5R7基團所取代。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -(C^-C6)烷基，而其任意地經1至3個分別選自氫、.齒素、 羥基、-N02、-CN、-(C^Ce)烷基、-(c2-c6)烯基、-(c2-C6)炔基、-C = N-OH、-C = N-OUC^-Ce)烷基）、-NR5R6、 -OR12、-（C3-C7)環烷基、-(C2-C9)雜環基、-C02Ri2、 一CONR5R6、-C〇nrsr8、_sr7、_s〇r7、一 s〇2r7、 一 S〇2NR5R6、-NHC〇R12、_NR12c〇nr5r6、和·Νκ125〇2Κ7 2 基團所取代，其中該R2基團之-(C2-C6)烯基和-(C2-C6)炔 基可任意地經1至3個R12基團所取代。 本發明亦提供一種式1所示之化合物，其中R2是_(c3-c7)環烷基或-(c2-c9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、_N02、-CN、_(C】-C6)烷基、-（C2_ C6)嫌基、-（C2-C6)炔基、-C = N- 〇H、-基）、_NR5R6、-OR12、-(C3-C7)環烷基、_(c2-c9)雜環基 、一C〇2R12、一CONR5R6、_c〇NR5r8、-sr7、一s〇r7、 -S02R7 h -S02NRsR6 ' -NHCOR12 ^ -NR12CONR5R6 ' •33- 200539871 (31) -NR12S〇2R7之基團所取代，其中該…基團之烯基 和- (C2_C6)炔基可任意地經1至3個R!2基團所取代。 本發明之另一體系是一種式1所示之化合物，其中R2 是-C〇2R12和- CONR5R6，而其任意地經1至3個分別選自氫 、鹵素、羥基、-no2、_CN、_(c厂C6)烷基、—（C2_C6)烯 基、_(c2-c6)炔基、-C = N —0H、—c = n_〇((Ci-C6)烷基）、 -NR5R6、-〇Ri2、—（c3 —C7)環烷基、—（C2_c9)雜環基、 -C〇2R12、一C〇NR5R6、一c〇NR5R8、-SR7、_SOR7、一S02R7 、-S〇2NRsR6、_NHC〇R12、一NR12CONR5R6、和一nr12so2r7 之基團所取代，其中該R2基團之—（C2-C6)烯基和_(C2_C6) 炔基可任意地經1至3個R 12基團所取代。 本發明亦提供一種式1所示之化合物，其中Ri是選自 氣、經基、和-(C^Ce)烷基，而其任意地經丨至3個分別選 自氫、鹵素、經基、-CN、-(CrCe)院基、-NR5R6、-OR12 、-(C3-C7)環烷基、-(c2-c9)雜環基、-C〇2r12、 - CONR5R6、和-CONR5R8之基團所取代；及！^是氫或-(Ci_ C6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-N02、-CN、-（CrCj 烷基、-（C2-C6)烯基、_(C2-C6)炔 基、-C = N-〇H > -¢ = 烷基）、-NR5R6、-OR12 、-（C3-C7)環烷基、-(C2-C9)雜環基、-C〇2r"、 一 CONR5R6、—C〇NR5R8、_SR7、一 S〇r7、_s〇2R7、 - S02NR5r6、- NHC〇R12、- NR12CONR5r6、和一NRi2S〇2R7 之 基團所取代，其中該R2基團之-(c2-c6)烯基和-((：2-0：6)炔 基可任意地經1至3個R12基團所取代。 -34 - 200539871 (32) 本發明亦提供一種式1所示之化合物，其中Ri是選自 氫、經基、和-（CrCd烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-（C】-C6)烷基、-NR5R6、- OR12 、-（C3-C7)環院基、-(C2-C9)雜環基、-c〇2R12、 - CONW、和—CONr5r8之基團所取代，·及r2是氫。 本發明亦提供一種式1所示之化合物，其中R1是- (Cr c 6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-(CrCj 烷基、-NR5R6、- OR"、_(C「C7)環烷基 、-（c2- c9)雜環基、_c〇2r12、-conr5r6、和- CONW之 基團所取代；及R2是氫。 本發明亦提供一種式1所示之化合物，其中R1是選自 一（CrC7)環烷基和-(c2-c9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、-CN、-（CrCj烷基、-NR5R6 、一0r12、-(c3-c7)環烷基、-(c2-c9)雜環基、-c〇2R12、 - CONRsR6、和一 conr5r8之基團所取代；及…是氫。 本發明亦提供一種式1所示之化合物，其中R1是選自 一〇(crC6)烷基、-o(c3-c7)環烷基、和-0(C2-C9)雜環基 ’而其任意地經1至3個分別選自氫、鹵素、羥基、-CN 、-(Ci_C6)烷基、_NR5R6、-OR12、-(C3-C7)環烷基、 -(c2 一 c9)雜環基、一C〇2R12、一CONR5R6、和-c〇NR5R8 之基 團所取代；及R2是氫。 本發明之一體系是一種式1所示之化合物，其中R1是 -NR5R6，而其任意地經1至3個分別選自氫、鹵素、經基 、-CN、-（c「C6)烷基、-NR5R6、-OR12、—（c「c：7)環烷基 -35- 200539871 (33) 、一（c2-c9)雜環基、一c〇2r12、—c〇nr5r6、手口、c〇nr5r8之 基團所取代；及R2是氫。 本發明之另一體系是一種式1所示之化合物，其中Ri 是 b 自-SR7、-SOR7、_S02R7、和-S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-（Ci-C6)院基 、-NR5R6、—〇Rl2、_((：；3<7)環烷基、-(C2 — C9)雜環基、 -C02R12、- CONR5R6、和-CONR5R8之基團所取代；及…是 •氫。 本發明亦提供一種式1所示之化合物，其中R1是 _C02R12、- CONW、- NHCOR12、- NR12CONR5R6、或 一NR12S02R7，而其任意地經！至3個分別選自氯、鹵素、經 基、-C N、- (c ! - C 6)院基、-N R5 R6、- 〇 R12、-（ C 3 - (3 7)環焼 基、-（C2 - C9)雜環基、-C02R12、-CONR5R6、和-c〇NR5R8 之基團所取代；及R2是氫。 | 本發明亦提供一種式1所示之化合物，其中r 2是氫或 _((^_(：6)烷基，而其任意地經2至3個分別選自氫、鹵素、 羥基、-N02、-CN、-(CrCe)烷基、-（C2-C6)烯基、_(c2-C6)炔基、-C = N_〇H、_C = N - 0(((：广(：6)烷基）、-NR5R6、 -OR】2、-(C3-C7)環烷基、-(C2-C9)雜環基、-C02R12、 - CONW、一CONR5R8、_sr7、_s〇r7、-s〇2R7、 _S〇2NR5R6、-NHCOR12、-NR12CONR5R6、和-NR12S02R7 之 基團所取代，其中該R2基團之-(C2-C6)烯基和-(0：2-(：6)炔 基可任意地經1至3個R12基團所取代；及1^是氫。 本發明亦提供一種式1所示之化合物，其中R2是-(C3- -36- 200539871 (34)-Ϊ́υ2Κ, -C〇NR5R6, -NHCOR] 2, -NR12C〇NR5R6, or -MK12S〇2R7, and any one of them is selected from hydrogen, _ prime, meridian, -CN,-(Ci -C6) an alkyl group, a nr5r6, _〇R ", a cycloalkyl group, a (C2-C9) heterocyclic group, a co2R12, _CONR5R6, and a co-NR5R8 group. In a preferred system, it is -NRl2s〇2R7, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(C1_C6) alkyl, -NR5R6, _〇Rl2,-(C3 —C7) cycloalkyl,-(C2-heterocyclyl, -C02R12, -CONR5R6, and a coNR5R7 group. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-( C ^ -C6) alkyl, which is optionally selected from 1 to 3 hydrogen, .dentin, hydroxyl, -N02, -CN,-(C ^ Ce) alkyl,-(c2-c6) ene ,-(C2-C6) alkynyl, -C = N-OH, -C = N-OUC ^ -Ce) alkyl), -NR5R6, -OR12,-(C3-C7) cycloalkyl,-( C2-C9) heterocyclyl, -C02Ri2, -CONR5R6, -Conrsr8, _sr7, _s〇r7, -s0227, -S02NR5R6, -NHC〇12, _NR12c0nr5r6, and Νκ125〇2κ7 2 The group is substituted, wherein-(C2-C6) alkenyl and-(C2-C6) alkynyl of the R2 group may be optionally substituted with 1 to 3 R12 groups. The present invention also provides a compound represented by Formula 1, wherein R2 is _ (c3-c7) cycloalkyl or-(c2-c9) heterocyclyl, and it is optionally selected from hydrogen and halogen through 1 to 3 , Hydroxyl, _N02, -CN, _ (C) -C6) alkyl,-(C2_C6) anhydroxyl,-(C2-C6) alkynyl, -C = N-OH, -yl), _NR5R6,- OR12,-(C3-C7) cycloalkyl, _ (c2-c9) heterocyclyl, -C02R12, -CONR5R6, -c〇NR5r8, -sr7, -sor7, -S02R7 h -S02NRsR6 '-NHCOR12 ^ -NR12CONR5R6 '• 33- 200539871 (31) -NR12S〇2R7 is substituted with an alkenyl group and-(C2_C6) alkynyl group of the ... group may optionally pass through 1 to 3 R! 2 groups To replace. Another system of the present invention is a compound represented by Formula 1, wherein R2 is -CO2R12 and -CONR5R6, and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -no2, _CN, _ (C plant C6) alkyl,-(C2_C6) alkenyl, _ (c2-c6) alkynyl, -C = N-0H, -c = n_〇 ((Ci-C6) alkyl), -NR5R6, -〇Ri2,-(c3-C7) cycloalkyl,-(C2_c9) heterocyclyl, -C〇2R12, -CONR5R6, -coNR5R8, -SR7, _SOR7, -S02R7, -S〇2NRsR6, _NHC〇R12, one NR12CONR5R6, and one nr12so2r7 are substituted, wherein the-(C2-C6) alkenyl and _ (C2_C6) alkynyl of the R2 group can be optionally passed through 1 to 3 R 12 groups. To replace. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from the group consisting of gas, meridian, and-(C ^ Ce) alkyl, and any one of them is selected from hydrogen, halogen, and meridian, respectively. , -CN,-(CrCe) courtyard, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -C〇2r12, -CONR5R6, and -CONR5R8 Replaced by the League; and! ^ Is hydrogen or-(Ci_C6) alkyl, and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(CrCj alkyl,-(C2-C6) alkenyl , _ (C2-C6) alkynyl, -C = N-〇H >-¢ = alkyl), -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocycle Group, -C〇2r ", -CONR5R6, -C〇NR5R8, _SR7, -Sor7, _s〇2R7, -S02NR5r6, -NHC〇R12, -NR12CONR5r6, and -NRi2S〇2R7, among which The-(c2-c6) alkenyl and-((: 2-0: 6) alkynyl of the R2 group may be optionally substituted with 1 to 3 R12 groups. -34-200539871 (32) The present invention also Provided is a compound represented by Formula 1, wherein Ri is selected from hydrogen, a hydroxyl group, and-(CrCd alkyl group, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(C ] -C6) alkyl, -NR5R6, -OR12,-(C3-C7) ring courtyard,-(C2-C9) heterocyclyl, -co2R12, -CONW, and -CONr5r8 are substituted, · And r2 are hydrogen. The present invention also provides a compound represented by Formula 1, wherein R1 is-(Cr c 6) alkyl, and it is optionally selected from hydrogen, halogen, and hydroxyl through 1 to 3 , -CN,-(CrCj alkyl, -NR5R6, -OR ", _ (C "C7) cycloalkyl,-(c2-c9) heterocyclyl, _c〇2r12, -conr5r6, and -CONW base And R2 is hydrogen. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of mono (CrC7) cycloalkyl and-(c2-c9) heterocyclyl, and optionally To 3 are selected from hydrogen, halogen, hydroxyl, -CN,-(CrCj alkyl, -NR5R6, -0r12,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl, -c. 2R12, -CONRsR6, and a conr5r8 group are substituted; and ... is hydrogen. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of 0 (crC6) alkyl, -o (c3-c7 ) Cycloalkyl, and -0 (C2-C9) heterocyclyl ', which are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(Ci_C6) alkyl, _NR5R6, -OR12, -(C3-C7) cycloalkyl,-(c2 -c9) heterocyclyl, -CO2R12, -CONR5R6, and -coNR5R8; and R2 is hydrogen. One system of the present invention is A compound represented by Formula 1, wherein R1 is -NR5R6, and it is arbitrarily selected from 1 to 3, respectively, selected from hydrogen, halogen, meridian, and -CN. -(C "C6) alkyl, -NR5R6, -OR12,-(c" c: 7) cycloalkyl-35- 200539871 (33), (c2-c9) heterocyclyl, -c02r12,- substituted with groups of conr5r6, hand mouth, conr5r8; and R2 is hydrogen. Another system of the present invention is a compound represented by Formula 1, wherein Ri is b from -SR7, -SOR7, _S02R7, and -S02NR5R6, and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(Ci-C6) courtyard, -NR5R6, -〇Rl2, _ ((:; 3 < 7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12,-CONR5R6, and- Is substituted by a group of CONR5R8; and ... is hydrogen. The present invention also provides a compound represented by Formula 1, wherein R1 is _C02R12, -CONW, -NHCOR12, -NR12CONR5R6, or -NR12S02R7, and it is optionally passed! To 3 are selected from the group consisting of chlorine, halogen, meridian, -CN,-(c! -C6), -N R5 R6, -〇R12,-(C 3-(3 7) cyclofluorenyl,- (C2-C9) Heterocyclyl, -C02R12, -CONR5R6, and -coNR5R8 are substituted; and R2 is hydrogen. The present invention also provides a compound represented by Formula 1, wherein r 2 is hydrogen or _ ((^ _ (: 6) alkyl, which is optionally selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(CrCe) alkyl,-(C2-C6) ene via 2 to 3 , _ (C2-C6) alkynyl, -C = N_〇H, _C = N-0 (((:( Broad (: 6) alkyl), -NR5R6,- OR] 2,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONW, -CONR5R8, _sr7, _s〇r7, -s〇2R7, _S〇2NR5R6, -NHCOR12 , -NR12CONR5R6, and -NR12S02R7, wherein-(C2-C6) alkenyl and-(0: 2-(: 6) alkynyl) of the R2 group can be optionally passed through 1 to 3 R12 groups And 1 ^ is hydrogen. The present invention also provides a compound represented by Formula 1, wherein R2 is-(C3- -36- 200539871 (34)

Gy)環烷基或-(CrCJ雜環基，而其任意地經1至3個分別選 自氫、鹵素、經基、-N〇2、-CN、—（Ci_C6)烷基、-(c2 — C6)嫌基、-(C2-C6)炔基、_c = N_〇H、-C = N —〇((c「以烷 基）、—NR5R6、-0R12、—（C3_C7)環烷基、-(C2-C9)雜環基 、-C02R12、一 CONR5R6、一 c〇nr5r8、一 sr7、一 s〇r7、 - S02R7、_s〇2NR5R6、_Nhc〇r"、一 nri2C〇nr5r6、和 _NR12S〇2R7之基團所取代，其中該…基團之_(c2 —Ce)烯基 和一（h-C6)炔基可任意地經1至3個1^2基團所取代；及…是 氣。 本發明之另一體系是一種式i所示之化合物，其中R2 是- C〇2R"和- CONR5R6，而其任意地經〗至3個分別選自氫 、歯素、經基、-no2、—CN、-(Ci-c6)烷基、-(C2-C6)烯 基、一（C2_C6)炔基、-C = N-〇H、-CcN-OUC!-c6)烷基）、 _nr5r6、—0R12、—（C3-C7)環烷基、-(C2-C9)雜環基、· -C02R12、一c〇NR5R6、一 c〇NR5R8、-SR7、- SOR7、- S02R7 、一 S〇2NR5r6、_NHC〇R12、- NR12CONR5R6、和-NR12S02R7 之基團所取代，其中該R2基團之-(C2-C6)烯基和-(C2-C6) 炔基可任意地經1至3個R!2基團所取代；及Rl是氫。 本發明亦提供一種式1所示之化合物，其中ri是選自 氨 > 經基、和—（Ci-C6)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、一（c「C6)烷基、-NR5R6、-OR12 、一（c3-c7)環烷基、—（C2_c9)雜環基、_c〇2R]2、 一 C〇NR5R6、和-CONR5R8之基團所取代；及R2是-(C^Ce) 烷基。 -37- 200539871 (35) 本發明亦提供一種式1所示之化合物，其中R1是-(Cr c6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-（C^-Ce)烷基、-NR5R6、-〇R12、-（C3_C7)環烷基 、-（C2-C9)雜環基、-C02R12、-CONR5R6、和-CONR5R8 之 基團所取代；及R2是-(C^Ce)烷基。 本發明亦提供一種式1所示之化合物，其中R1是選自 -（C3-C7)環烷基和-(c2-C9)雜環基，而其任意地經1至3個 •分別選自氫 '鹵素、羥基、-CN、-(C^-Ce)烷基、-NR5R6 、-OR12、-（C3-C7)環烷基、-(C2-C9)雜環基、-C02R12、 - CONR5R6、和一 c〇NR5R8之基團所取代；及R2是一 (C「C6) 烷基。 本發明亦包含一種式1所示之化合物，其中R1是選自 一 0(C广C6)烷基、-〇(C3-C7)環烷基、和-0(c2-c9)雜環基 ，而其任意地經1至3個分別選自氫、鹵素、羥基、-CN _ 、-(CrC6)烷基、-NR5R6、_〇R12、-（C3-C7)環烷基、 - (C2 - C9)雜環基、一 C〇2Ri2、_c〇nr5r6、和一 c〇nr5r8 之基 團所取代；及R2是-(q-C6)烷基。 本發明之一體系是一種式1所示之化合物，其中R1是 _NR5R6 ,而其任意地經1至3個分別選自氫、鹵素、羥基 、一 CN、-（C「C6)烷基、一 Nr5r6、一〇R12、一（^一^)環烷基 、一 (C2〜C9)雜環基、-C02R12、- CONR5R6、和- c〇NR5R8 之 基團所取代；及R2是-(Ci-C6)烷基。 本發明之另一體系是一種式1所示之化合物，其中R1 是選自-SR7、-SOR7、-S02R7、和- S02NR5R6,而其任意地 -38- 200539871 (36) 經1至3個分別選自氫、鹵素、經基、_CN、-（C^-Ce)院基 、-NR5R6、-〇R12、-(C3-C7)環烷基、-(c2-c9)雜環基、 -C02R12、-CONR5R6、和-CONR5R8 之基團所取代；及 R2 是-（c i-C6)烷基。 本發明亦提供一種式1所示之化合物，其中R1是 一 C02R12、-CONR5R6、一 NHCOR12、一 NR12CONR5R6、或 - NR12S02R7，而其任意地經1至3個分別選自氫、齒素、羥 基、-CN、-（CrCe)烷基、-NR5R6、-OR12、-(C3-C7)環烷 基、-(c2-c9)雜環基、-co2r12、-c〇nr5r6、和 _conr5r8 之基團所取代；及R2是-(Cl-C6)烷基。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -（CrCd烷基，而其任意地經1至3個分別選自氫、鹵素、 羥基、-n〇2、-CN、一（Ci-C6)烷基、一（C2_c6)烯基、一（<：2一 c6)炔基、一 c = N-〇H、-C = N-〇((C】- C6)烷基）、-NR5R6、 — 〇Rl2、_(C3一C7)環烷基、_(C2-C9)雜環基、-C02R12、 一 CONR5r6 ' -C〇NR5R8、-SR7、-S〇R7、-S02R7、 -S〇2NR5r6、一 NHC〇R12、_NR12C〇NR5R6、和一 NR12S02R7 之 基團所取代，其中該R2基團之-(c2_c6)烯基和-（(：2-(：6)炔 基可任意地經1至3個R12基團所取代；及R1是_(Ci —c6)烷基 〇 本發明亦提供一種式1所示之化合物，其中R2是-(C3-c?)環院基或-(c2 —C9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-N〇2、—CN、烷基、_(Cr c6)烯基、〜（C2 —炔基、-C = N —〇H、-C = N —〇((Ci —cj烷 -39- 200539871 (37) 基） nr5r6 〇R12、 C02R12、-CONR5R6、 一（C3-c7)環烷基、-(c2_c9)雜環基 CONR5R8，-SR7 ' -SOR7 ' - so/、- S〇2NW …NHC〇Rl2、—nr12c〇nr5r6、和 NR S〇2R之基團所取代，其巾該R2基團之-（C2-C6)嫌基 和（^2 C6)炔基可任意地經1至3個1^2基團所取代；及… 是-（CrCd烷基。Gy) cycloalkyl or-(CrCJ heterocyclyl), which are optionally selected from hydrogen, halogen, meridian, -N〇2, -CN,-(Ci_C6) alkyl,-(c2 — C6) alkyl,-(C2-C6) alkynyl, _c = N_〇H, -C = N —〇 ((c "as alkyl", -NR5R6, -0R12,-(C3_C7) cycloalkyl ,-(C2-C9) heterocyclyl, -C02R12, one CONR5R6, one conr5r8, one sr7, one sor7,-S02R7, _s〇2NR5R6, _Nhc〇r ", one nri2Cnr5r6, and _NR12S 〇2R7 is replaced by a group in which _ (c2-Ce) alkenyl and mono (h-C6) alkynyl of the ... group may be optionally substituted with 1 to 3 1 ^ 2 groups; and ... Another system of the present invention is a compound represented by formula i, wherein R2 is -CO2R "and -CONR5R6, and any one of them is selected from hydrogen, halogen, sulfonyl,- no2, —CN,-(Ci-c6) alkyl,-(C2-C6) alkenyl, mono (C2-C6) alkynyl, -C = N-OH, -CcN-OUC! -c6) alkyl), _nr5r6, -0R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -coNR5R6, -coNR5R8, -SR7, -SOR7, -S02R7, -S 〇2NR5r6, _NHC〇R1 2,-NR12CONR5R6, and -NR12S02R7 are substituted, wherein the-(C2-C6) alkenyl and-(C2-C6) alkynyl of the R2 group can be optionally passed through 1 to 3 R! 2 groups And R1 is hydrogen. The present invention also provides a compound represented by Formula 1, wherein ri is selected from the group consisting of ammonia >, and-(Ci-C6) alkyl, and optionally 1-3 Selected from the group consisting of hydrogen, halogen, hydroxy, -CN, mono (c "C6) alkyl, -NR5R6, -OR12, mono (c3-c7) cycloalkyl,-(C2_c9) heterocyclyl, _c〇2R] 2 , -CONR5R6, and -CONR5R8; and R2 is-(C ^ Ce) alkyl. -37- 200539871 (35) The present invention also provides a compound represented by Formula 1, wherein R1 is- (Cr c6) alkyl, which is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN,-(C ^ -Ce) alkyl, -NR5R6, -〇R12,-(C3_C7) rings Substituted with alkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8; and R2 is-(C ^ Ce) alkyl. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of-(C3-C7) cycloalkyl and-(c2-C9) heterocyclyl, and is optionally selected from 1 to 3 Hydrogen 'halogen, hydroxy, -CN,-(C ^ -Ce) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6 And R 2 are substituted by a group of coNR5R8; and R 2 is a (C "C6) alkyl group. The present invention also includes a compound represented by Formula 1, wherein R 1 is selected from a 0 (C 2 C 6) alkyl group , -〇 (C3-C7) cycloalkyl, and -0 (c2-c9) heterocyclyl, which are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN_,-(CrC6) Substituted with alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -CO2Ri2, -conon5r6, and -conon5r8; And R2 is-(q-C6) alkyl. One system of the present invention is a compound represented by Formula 1, wherein R1 is _NR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(C "C6) alkyl, -Nr5r6, -OR12,-(^ a ^) cycloalkyl,-(C2 ~ C9) heterocyclyl, -C02R12, -CONR5R6, and -c NR5R8 is substituted with a group; and R2 is-(Ci-C6) alkyl. Another system of the present invention is a compound represented by Formula 1, wherein R1 is selected from -SR7, -SOR7, -S02R7, and- S02NR5R6, and it is arbitrarily -38- 200539871 (36) selected from 1 to 3 respectively selected from hydrogen, halogen, base, _CN,-(C ^ -Ce) base, -NR5R6, -〇R12,-(C3 -C7) cycloalkyl,-(c2-c9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8; and R2 is-(c i-C6) alkyl. The invention also provides a A compound represented by Formula 1, wherein R1 is -C02R12, -CONR5R6, -NHCOR12, -NR12CONR5R6, or -NR12S02R7, and it is optionally selected from 1 to 3, respectively, selected from hydrogen, halide, hydroxyl, -CN,-( CrCe) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -co2r12, -cONr5r6, and _conr5r8; and R2 Is-(Cl-C6) alkyl. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-(CrCd alkyl, and it is optionally selected from hydrogen, halogen, and hydroxyl through 1 to 3 , -N〇2, -CN, mono (Ci-C6) alkyl, mono (C2_c6) alkenyl, mono (< : 2-c6) alkynyl, -c = N-〇H, -C = N-〇 ((C) -C6) alkyl), -NR5R6, -〇Rl2, _ (C3-C7) cycloalkyl, _ (C2-C9) heterocyclyl, -C02R12, -CONR5r6 '--CONR5R8, -SR7, -SOR7, -S02R7, -S〇2NR5r6, -NHCOR12, -NR12C〇NR5R6, and -NR12S02R7 Group, wherein-(c2_c6) alkenyl and-((: 2-(: 6) alkynyl) of the R2 group may be optionally substituted with 1 to 3 R12 groups; and R1 is _ (Ci —C6) alkyl. The present invention also provides a compound represented by Formula 1, wherein R2 is a-(C3-c?) Cycloalkyl or-(c2-C9) heterocyclyl, and it is optionally Each is selected from the group consisting of hydrogen, halogen, hydroxyl, -N02, -CN, alkyl, _ (Cr c6) alkenyl, ~ (C2-alkynyl, -C = N-〇H, -C = N-〇 ((Ci —cj alkane-39- 200539871 (37) group) nr5r6 〇R12, C02R12, -CONR5R6, mono (C3-c7) cycloalkyl,-(c2_c9) heterocyclyl CONR5R8, -SR7 '-SOR7'- so /,-S〇2NW… NHC〇Rl2, -nr12c〇nr5r6, and NR S〇2R groups are substituted, which is the-(C2-C6) aryl group and (^ 2 C6) alkyne of the R2 group The radical can be optionally passed through 1 to 3 1 ^ 2 groups Substituted; and ... is - (CrCd alkyl.

本發明之另一體系是一種式1所示之化合物，其中R2 是- COW12和- CONR5r6，而其任意地經1至3個分別選自氫 、鹵素、經基、-n〇2、一CN、·（◦广^)院基、—（C「C6)嫌 基、-(c2-c6)炔基、-C = N 一 0H、-C==N —〇((c「C6)烷基）、 _NR5R6、〜〇R12、_(C3 —C7)環烷基、-（c2-c9)雜環基、 -C0,R: -CONR5R6、-c〇NR5R8、-SR7、-SOR7、-S09R7 、-S02NR5R6、一 nhcor12、_nr12c〇nr5r6、和一 nr12s〇2R7 之基團所取代，其中該R2基團之-(c2-c6)烯基和-(c2-c6) 炔基可任意地經1至3個R12基團所取代；及1^1是-(Ci-C6)烷 基。 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、羥基、和-((：「(：6)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-(C〗-C6)烷基、-NR5R6、-OR12 、一（CrC7)環烷基、-(c2-c9)雜環基、-C〇2Ri2、 - CONR5R6、和-CONR5R8之基團所取代；R2是氫或-(c】-c 6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-N〇2、-CN、-（C「C6)烷基、-（C2-C6)烯基、-(C2-C6)炔 基、- C = N - 〇H、-CsN-OUC^Cj 烷基）、- NR5R6、- 〇R12 -40 - 200539871 (38) 、-（C3-C7)環烷基、-(c2-C9)雜環基、-c〇2r12、 -CONR5R6 ' 一CONR5R8、_sr7、一s〇r7、一sc^r7、 -so2nr5r6、_NHC0R12、-nr12c〇nr5r6、和一NRl2s〇2R7之 基團所取代，其中該R2基團之—（C2_C6)烯基和-((：2-(：6)炔 基可任意地經1至3個R12基團所取代；及η是1。 本發明亦提供一種式1所示之化合物，其中Ri是選自 _ 氫、經基、和-(C^-Ce)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-(Ci-Cj烷基、-NR5R6、-OR12 、一（c3-c7)環烷基、-(c2-C9)雜環基、-c〇2ri2、 -CONW、和_c〇nr5r8之基團所取代；R$_(c广C6)院 基；及η是1。 本發明亦提供一種式1所示之化合物，其中ri是- (Cj-C6)院基’而其任意地經〗至3個分別選自氫、鹵素、羥基 、-CN、-（Cl-C6)烷基、-NR5R6、- OR"、一（c「C7)環烷基 .、-(c2-c9)雜環基、一 C02R12、一CONR5R6、和 _CONR5R8 之 基團所取代；R2是-(C^CJ烷基；及n是1。 本發明亦提供一種式1所示之化合物，其中Ri是選自 一（CrC7)環烷基和-(c2-c9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、-CN、-(C丨-C6)烷基、-NR5R6 、-〇r12、-(c3-c7)環烷基、-(c2-c:9)雜環基、—c：〇2Rl2、 - CONW、和—c〇nr5r8之基團所取代；r2是_(C「C6)院 基；及η是1。 本發明亦包含一種式1所示之化合物，其中Ri是選自 一 〇(CrC6)烷基、-〇(C3-C7)環烷基、和- 〇(C2-C9)雜環基 -41 - 200539871 (39) ，而其任意地經1至3個分別選自氫、鹵素、羥基、-CN 、一（C「C6)烷基、-NR5R6、- OR12、-(C3 - C7)環烷基、 一（c2 - C9)雜環基、-C〇2R12、-CONFER6、和一c〇NR5R8 之基 團所取代；R2是- 烷基；及11是1。 本發明之一體系是一種式1所示之化合物，其中R1是 -NR5R6，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-(Cl-C6)烷基、-NR5R6、-〇R12、-（c3 一 C7)環烷基 、-(C2-C9)雜環基、_C〇2R12、-CONR5R6、和一 c〇nr5r82 基團所取代；R2是-(C^Cd烷基；及n是1。 本發明之另一體系是一種式1所示之化合物，其中R1 是選自-SR7、-SOR7、-S02R7、和-S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-cm、—（Ci_c6)烷基 、-nr5r6、-OR"、-(C3-c7)環烷基、-(C2-C9)雜環基、 - C02R12、-CONR5R6、和-CONR5R8之基團所取代；…是 -（h-C6)院基；及11是1。 本發明亦提供一種式1所示之化合物，其中Ri是 - C02R12、- CONW、- NHC0R12、- NR12C0NW、或 —NR12S02R7，而其任意地經1至3個分別選自氫、鹵素、經 基、-CN、-(CrCe)烷基、_NR5R6、_0R12、-(C3-C7)環烷 基、-（C2 - C9)雜環基、_C02R12、- CONR5R6、和一c〇NR5R8 之基團所取代；R2是-（CVCd烷基；及η是1。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -（(：厂(：6)烷基，而其任意地經1至3個分別選自氫、鹵素、 經基、-N02、-CN、-(CrC6)焼基、-(c2-c6)嫌基、-(c2 - -42· 200539871 (40) c6)炔基、-c = N- 〇H、-ON - 〇（（CrC6)院基）、-nr5r6、 一0Rl2、—（C3 —c7)環院基、-(c2-c9)雜環基、_c〇2R12、 -CONR5R6、一c〇nr5r8、_sr7、—s〇r7、s〇2r7、 -so2nr5r6、_nhcor12、—nr"c〇nr5r6、和—nr12s〇2R7 基團所取代，其中該R2基團之-(C2_C6)烯基和_(C2_C6)炔 基可任意地經1至3個R12基團所取代；1^是-((：1-〇6)烷基； 及η是1。 $ 本發明亦提供一種式1所示之化合物，其中r2是_(c3_ C7)環烷基或-（C2-C9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-N02、-CN、-(C^-Ce)烷基、-（C2-C6)嫌基、-（C2-C6)炔基、-C = N-〇H、-C = N-〇((C「C6)烷 基）、-NR5R6、-OR”、—（C3_c7)環烷基、-(c2-c9)雜環基 、-C02R12、_CONR5R6、一CONR5R8、一 SR7、一 s〇R7、 - S02R7、-S02NR5R6、-NHC0R12、- NR12CONR5R6、和 -nr12so2r7之基團所取代，其中該R2基團之-(c2-c6)烯基 和-（C2-C6)炔基可任意地經1至3個R12基團所取代；R1是 一（Ci-C6)烷基；及η是1。 本發明之另一體系是一種式1所示之化合物，其中R2 是-C02R12和-CONR5R6，而其任意地經1至3個分別選自氫 、_素、羥基、-Nog、- CN、-（C^-Ce)院基、-(c2-c6)嫌 基、_(C2_C6)炔基、-C = N_〇H、-CtN-OUC^-Ce)烷基）、 - NR5R6、- OR12、-（C3-C7)環烷基、-（C2-C9)雜環基、 -C02R12、-CONR5R6、-CONR5R8、-SR7、-SOR7、-S02R7 、一S〇2NR5R6、-NHCOR12、-NR12C〇NR5R6、和-NR12S〇2R7 -43- 200539871 (41) 之基團所取代，其中該R2基團之-(c2-c6)烯基和-（c2-c6) 炔基可任意地經1至3個R12基團所取代；是-(Ci —c6)烷基 ;及n是1。 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、羥基、和-(C广C6)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-(C!-C6)院基、-NR5R6、_OR12 、-（C3-C7)環烷基、—（c2-c9)雜環基、—c〇2r12、 -conr5r6、和-CONr5r8之基團所取代；r2是_(c广c6)院 基；及η是1。 本發明亦提供一種式1所示之化合物，其中R1是- ((^-Ce)院基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-（C「C6)烷基、-NR5R6、-OR12、-（C3-C7)環烷基 、-(C2-C9)雜環基、-c〇2R12、_CONR5R6、和-CONR5R8 之 基團所取代；R2是-(C^CJ烷基；及n是1。 本發明亦提供一種式1所示之化合物，其中Ri是選自 -（CrC7)環烷基和-(c2-c9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、—CN、-（(：广(：6)烷基、-NR5R6 、-OR12、-（C3-C7)環烷基、—（c2-C：9)雜環基、—c〇2R】2、 - CONW、和 _conr5r8 之基團所取代；r：^_(Ci_C6)院 基；及η是1。 本發明亦包含一種式1所示之化合物，其中Ri是選自 -〇(c】-c6)烷基、-〇(C3-C7)環烷基、和-〇(C「C9)雜環基 ，而其任意地經1至3個分別選自氫、鹵素 '羥基、-CN 、-(Crc6)烷基、-nr5r6、_〇Ri2、—（C3 — c7)環烷基、 -44 - 200539871 (42) 一（C2~C9)雜環基、一C〇2R12、-CONR5R6、和—conr5r8 之基 團所取代；R2是-(C^-Ce)烷基；及η是1。 本發明之一體系是一種式1所示之化合物，其中R1是 - NR5R6，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-(c「C6)烷基、-NR5R6、_〇R12、-(C3 - C7)環烷基 、-(C2-C9)雜環基、-C02R12、-CONR5R6、和一 c〇nr5r8$ 基團所取代；R2是- (C^-Ce)院基；及η是1。 本發明之另一體系是一種式1所示之化合物，其中R1 是選自-SR7、-SOR7、-S02R7、和- S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-(Ci-c6)烷基 、-NR5R6、_〇R"、_(C3-(：7)環烷基、-(C2-C9)雜環基、 - C02R12、-CONR5R6、和-CONR5R8 之基團所取代；R2 是 -(C^-C6)院基；及η是1。 本發明亦提供一種式1所示之化合物，其中Ri是 -C02R】2、-CONR5R6、—NHC0R12、-NR12CONR5R6、或 一 NR12S02R7，而其任意地經1至3個分別選自氫、鹵素、羥 基、-CN、-（C「C6)烷基、_NR5R6、_0R12、-(C「c7)環烷 基、—（C2 - C9)雜環基、-C〇2R12、一C〇NR5r6、和一c〇NR5R8 之基團所取代；R2是-(CVC6)烷基；及11是1。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -((^-(：6)烷基，而其任意地經1至3個分別選自氫、鹵素、 羥基、-N02、-CN、_(CrC6)烷基、-(C2-C6)烯基、_(C2-C6)炔基、一 C = N — 〇H、= 垸基）、一NR5R6、 -〇R12、-(C3-C7)環烷基、-(C2-C9)雜環基、-C02R12、 -45- 200539871 (43) -CONR5R6、-C〇NR5R8、-SR7、—S〇R7、—S〇2R7、 - S〇2NR5R6、_NHC〇R12、一 NR12c〇NR5R6、和-NR12S02R7 之 基團所取代，其中該R2基團之-(C2-C6)烯基和—（C2_C6)炔 基可任意地經1至3個R"基團所取代；…是、…“」烷基； 及η是1。 本發明亦提供一種式1所示之化合物，其中R2是_(C3_ C7)環烷基或-（(：2_<：9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-N02、-CN、-(CrCj烷基、-(C2-c6)嫌基、-（C2-C6)炔基、-c = N-〇H、-C = N-0((C「C6)焼 基）、-NR5R6、-OR"、_(c广C7)環烷基一（c广雜環基 、-C02R12、-CONR5R6、一 CONR5R8、_sr7、_s〇r7、 -S02R7、-S02NR5Re、-NHCOR12、-NR12CONR5R6、和 -NR12s〇2R7之基團所取代，其中該…基團之_(C2-C6)烯基 和-（C2_(：6)炔基可任意地經1至3個基團所取代；…是 一（Ci"~C6)院基；及 η是 1。 本發明之另一體系是一種式i所示之化合物，其中R2 是-CO2。2和-CONr5R6，而其任意地經iS3個分別選自氫 、鹵素、羥基、-no2、-CN、-(C^C6)烷基、—（C2_C6)嫌 基、-(C2-C6)炔基一C = N-〇H、_c = N — 〇((Ci —y烷基）、 _NR5R6、—〇R12、-(cfC7)環烷基、-（C2-C9)雜環基、 -co2r12、一conr5r6、一c〇nr5r8、一sr7、一s〇r7、_s〇2R7 、-S02NR5R6、_nhc〇r12、_nr12c〇nr5r6、和一遞i2s〇2R7 之基團所取代，其中Kr2基團之_(C「C6)烯基和一 (c「c6) 炔基可任意地經1至3個1^2基團所取代；烷基 -46- 200539871 (44) ;及η是1。 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、羥基、和-（C^Ce)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-(CrCe)烷基、-NR5R6、-OR12 、-(C3-C7)環烷基、-（C2-C9)雜環基、-C02R12、 - CONR5R6、和一c〇nr5r^基團所取代；R2是氫或一（C「 C6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 ® 、-N02、-CN、-(C「C6)烷基、-（C2-C6)烯基、-（C2-C6)炔 基、- C = N-〇H、_C = N-〇((CrC6)烷基）、- NR5R6、- OR12 、-(C3-C7)環烷基、-（C2-C9)雜環基、-c〇2R12、 一CONFER6、一CONR5R8、_sr7、_s〇r7、一s〇2r7、 一 S02NR5r6、_NHC〇R12、-NR12C〇NR5r6、和 _NR12S02R7 之 基團所取代，其中該R2基團之-(c2-c6)烯基和-(c2-c6)炔 基可任意地經1至3個R12基團所取代；及η是1。 g 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、羥基、和- 烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-（C^U 烷基、-NR5R6、-〇R12 、-（C3-C7)環烷基、-(C2-C9)雜環基、-c〇2R】2、 - CONR5R6、和-CONR5R8之基團所取代；r2是氣；及n是1 〇 本發明亦提供一種式1所示之化合物，其中R1是- (C!-c6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-(Ci-Ce)院基、-NR5R6、- 〇R"、_(c3-C7)環院基 、-（C2-C9)雜環基、-C02R】2、-C〇NR5R6、和- C〇NR5R8 之 -47- 200539871 (45) 基團所取代；R2是氫；及n是1。 本發明亦提供一種式1所示之化合物，其中Ri是選自 -（CrC7)環烷基和—（C2_C9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、_CN、-(c^-Ce)烷基、-NR5R6 、一0Rl2、—（c3 - 匸7)環烷基、-（C2 - C9)雜環基、—c〇2r”、 - CONR5R6、和—c〇nr5r8之基團所取代；r2是氫；及11是1 〇 • 本發明亦包含一種式1所示之化合物，其中R1是選自 一 〇(^Μ6)烷基、-〇(C3-C7)環烷基、和-〇(C2-C9)雜環基 ’而其任意地經1至3個分別選自氫、鹵素、羥基、-c N 、-(CrCd 烷基、_NR5R6、-OR12、_(C3-C7)環烷基、 -（C2-C9)雜環基、一C〇2R12、-CONR5R6、和-CONR5R8之基 團所取代；R2是氫；及η是1。 本發明之一體系是一種式1所示之化合物，其中R1是 一 NR5R6，而其任意地經1S3個分別選自氯、鹵素、經基 •、-CN、-（C「C6)烷基、-NR5R6、- OR12、_(C3-C7)環烷基 、-(C2-C9)雜環基、-C02R12、-CONR5R6、和一 CONW 之 基團所取代；R2是氫；及11是1。 本發明之另一體系是一種式1所示之化合物，其中R1 是選自-SR7、-SOR7、-S02R7、和-S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-(C^Ce)烷基 、-NR5R6、-OR"、—（c3-c7)環烷基、-(C2-C9)雜環基、 一 C〇2R12、一 CONR5R6、和-CONR5R8之基團所取代；R2是氫 ;及n是1。 -48- 200539871 (46) 本發明亦提供一種式1所示之化合物，其中R1是 —C〇2R12、一CONR5R6、一NHCOR12、_NR12C〇NR5r6、或 _NR12S02R7，而其任意地經！至3個分別選自氫、鹵素、羥 基、-CN、-(C「C6)烷基、-NR5R6、-OR12、-（C3-C7)環烷 基、一（C2-C9)雜環基、一C〇2R12、一C〇NR5R6、禾口一CONR5R8 之基團所取代；R2是氫；及η是1。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -（C^Ce)烷基，而其任意地經丨至3個分別選自氫、鹵素、 羥基、-N02、-CN、-（CrCj 烷基、-（C2-C6)烯基、-（c2-C6)炔基、-C = N-OH、- C = N-0(((^-(^)烷基）、-NR5R6、 - OR12、-(C3-C7)環烷基、-(c2-C9)雜環基、-C02R12、 一 C〇NR5r6、一 c〇NR5R8、一SR7、_S〇R7、一 S02R7、 -S02NR5R6、-NHCOR12、-NR12CONR5R6、和-NR12S02R7 之Another system of the present invention is a compound represented by Formula 1, wherein R2 is -COW12 and -CONR5r6, and it is optionally selected from 1 to 3, respectively, selected from hydrogen, halogen, meridian, -n02, -CN. , (◦ 广 ^) Yuanji, — (C 「C6) alkynyl,-(c2-c6) alkynyl, -C = N-0H, -C == N —〇 ((c「 C6) alkyl ), _NR5R6, ~ 〇R12, _ (C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -C0, R: -CONR5R6, -coNR5R8, -SR7, -SOR7, -S09R7, -S02NR5R6, a nhcor12, _nr12c0nr5r6, and a nr12s02R7 group, wherein-(c2-c6) alkenyl and-(c2-c6) alkynyl of the R2 group can be optionally passed through 1 to 3 R12 groups are substituted; and 1 ^ 1 is-(Ci-C6) alkyl. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from hydrogen, hydroxyl, and-((: "( : 6) alkyl, which is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN,-(C〗 -C6) alkyl, -NR5R6, -OR12, mono (CrC7) cycloalkyl ,-(C2-c9) heterocyclyl, -C02Ri2, -CONR5R6, and -CONR5R8; R2 is hydrogen or-(c) -c 6) alkyl, and it is optionally 3 are selected from , Halogen, hydroxy, -N〇2, -CN,-(C "C6) alkyl,-(C2-C6) alkenyl,-(C2-C6) alkynyl, -C = N-〇H, -CsN -OUC ^ Cj alkyl), -NR5R6, -〇R12 -40-200539871 (38),-(C3-C7) cycloalkyl,-(c2-C9) heterocyclyl, -c〇2r12, -CONR5R6 ' A CONR5R8, _sr7, a so7, a sc ^ r7, -so2nr5r6, _NHC0R12, -nr12c〇nr5r6, and an NRl2s〇2R7 group, wherein the-(C2_C6) alkenyl and- ((: 2-(: 6) alkynyl can be optionally substituted with 1 to 3 R12 groups; and η is 1. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from hydrogen, Via a radical, and-(C ^ -Ce) alkyl, and optionally via 1 to 3, respectively, selected from hydrogen, halogen, hydroxyl, -CN,-(Ci-Cj alkyl, -NR5R6, -OR12, one (C3-c7) cycloalkyl,-(c2-C9) heterocyclyl, -c〇2ri2, -CONW, and -cONr5r8; R $ _ (c 广 C6) courtyard; and η is 1. The present invention also provides a compound represented by Formula 1, wherein ri is-(Cj-C6), and it is optionally selected from three to three selected from hydrogen, halogen, hydroxyl, -CN,- (Cl-C6) alkyl, -NR5R 6, -OR ", a (c "C7) cycloalkyl.--(C2-c9) heterocyclyl, a C02R12, a CONR5R6, and _CONR5R8 groups; R2 is-(C ^ CJ alkyl Base; and n is 1. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from mono (CrC7) cycloalkyl and-(c2-c9) heterocyclyl, and it is optionally selected from hydrogen and halogen via 1 to 3 , Hydroxyl, -CN,-(C 丨 -C6) alkyl, -NR5R6, -〇r12,-(c3-c7) cycloalkyl,-(c2-c: 9) heterocyclyl, -c: 〇2Rl2 , -CONW, and -connr5r8; r2 is-(C "C6); and η is 1. The present invention also includes a compound represented by Formula 1, wherein Ri is selected from the group consisting of (CrC6) alkyl, -〇 (C3-C7) cycloalkyl, and -〇 (C2-C9) heterocyclyl-41-200539871 (39), which are optionally selected from hydrogen through 1 to 3, Halogen, hydroxy, -CN, mono (C "C6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl, mono (c2-C9) heterocyclyl, -C〇2R12, -CONFER6, And a co-NR5R8 group; R2 is -alkyl; and 11 is 1. One system of the present invention is a compound represented by Formula 1, wherein R1 is -NR5R6, and it is optionally Selected from hydrogen, halogen, hydroxyl, -CN,-(Cl-C6) alkyl, -NR5R6, -〇R12,-(c3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C 2R12, -CONR5R6, and a conr5r82 group; R2 is-(C ^ Cd alkyl; and n is 1. Another system of the present invention is a compound represented by Formula 1, wherein R1 is selected from -SR7, -SOR7, -S02R7, and -S02NR5R6, which are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -cm,-(Ci_c6) alkyl, -nr5r6, -OR ",-( C3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 are substituted by; ...-(h-C6) courtyard; and 11 is 1. The invention also provides a compound represented by Formula 1, wherein Ri is -CO2R12, -CONW, -NHC0R12, -NR12C0NW, or -NR12S02R7, and it is optionally selected from 1 to 3 selected from hydrogen, halogen, meridian,- CN,-(CrCe) alkyl, _NR5R6, _0R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, _C02R12, -CONR5R6, and a co-NR5R8 group; R2 Is-(CVCd alkyl; and η is 1. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-((: ((6) alkyl), and it is optionally passed through 1 to 3 Selected from hydrogen, halogen, meridian, -N02, -CN,-(CrC6) fluorenyl,-( c2-c6) alkyl,-(c2--42 · 200539871 (40) c6) alkynyl, -c = N- 〇H, -ON-〇 ((CrC6) courtyard), -nr5r6, -0Rl2,- (C3--c7) ring courtyard group,-(c2-c9) heterocyclic group, _c〇2R12, -CONR5R6, -conr5r8, _sr7, -s〇r7, s〇2r7, -so2nr5r6, _nhcor12, -nr " c〇nr5r6, and -nr12s〇2R7 groups, wherein-(C2_C6) alkenyl and _ (C2_C6) alkynyl of the R2 group may be optionally substituted with 1 to 3 R12 groups; 1 ^ is -((: 1-〇6) alkyl; and n is 1. The present invention also provides a compound represented by Formula 1, wherein r2 is _ (c3_C7) cycloalkyl or-(C2-C9) heterocyclyl, and it is optionally selected from hydrogen and halogen through 1 to 3 , Hydroxyl, -N02, -CN,-(C ^ -Ce) alkyl,-(C2-C6) alkyl,-(C2-C6) alkynyl, -C = N-OH, -C = N- 〇 ((C "C6) alkyl), -NR5R6, -OR",-(C3_c7) cycloalkyl,-(c2-c9) heterocyclyl, -C02R12, _CONR5R6, -CONR5R8, -SR7, -s R7, -S02R7, -S02NR5R6, -NHC0R12, -NR12CONR5R6, and -nr12so2r7 are substituted with the-(c2-c6) alkenyl and-(C2-C6) alkynyl of the R2 group 1 to 3 R12 groups are substituted; R1 is a (Ci-C6) alkyl group; and n is 1. Another system of the present invention is a compound represented by Formula 1, wherein R2 is -C02R12 and -CONR5R6, and it is arbitrarily selected from 1 to 3 selected from hydrogen, hydrogen, hydroxyl, -Nog, -CN,- (C ^ -Ce) Yakimoto,-(c2-c6) alkyl, _ (C2_C6) alkynyl, -C = N_〇H, -CtN-OUC ^ -Ce) alkyl),-NR5R6,-OR12 ,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -S02R7, -S02NR5R6, -NHCOR12, -NR12C. NR5R6, and -NR12S〇2R7 -43- 200539871 (41), in which-(c2-c6) alkenyl and-(c2-c6) alkynyl of the R2 group can be optionally passed through 1 to 3 Each R12 group is substituted; is-(Ci -c6) alkyl; and n is 1. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from hydrogen, hydroxyl, and-(C-C6) alkyl, and it is optionally selected from hydrogen, halogen, hydroxyl,- CN,-(C! -C6) courtyard, -NR5R6, _OR12,-(C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -c〇2r12, -conr5r6, and -CONr5r8 Group is replaced; r2 is _ (c 广 c6) 院 基; and η is 1. The present invention also provides a compound represented by Formula 1, wherein R1 is-((^-Ce), and is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(C " C6) substituted with alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -co2R12, _CONR5R6, and -CONR5R8; R2 is- (C ^ CJ alkyl; and n is 1. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from-(CrC7) cycloalkyl and-(c2-c9) heterocyclyl, and any The ground warp 1 to 3 are selected from the group consisting of hydrogen, halogen, hydroxyl, -CN,-((: wide (: 6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(c2- C: 9) Heterocyclyl, —co2R] 2, —CONW, and —conr5r8 are substituted; r: (Ci_C6); and η is 1. The present invention also includes a formula 1 A compound represented by the formula wherein Ri is selected from the group consisting of -0 (c) -c6) alkyl, -0 (C3-C7) cycloalkyl, and -0 (C "C9) heterocyclyl, which are optionally 3 are selected from hydrogen, halogen 'hydroxyl, -CN,-(Crc6) alkyl, -nr5r6, -〇Ri2,-(C3-c7) cycloalkyl, -44-200539871 (42)-(C2 ~ C9 Heterocyclyl -Co2R12, -CONR5R6, and -conr5r8 are substituted; R2 is-(C ^ -Ce) alkyl; and η is 1. One system of the present invention is a compound represented by Formula 1, wherein R1 Is-NR5R6, which is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(c "C6) alkyl, -NR5R6, -〇R12,-(C3-C7) cycloalkyl ,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and a conr5r8 $ group; R2 is-(C ^ -Ce) group; and η is 1. Another of the present invention The system is a compound represented by Formula 1, wherein R1 is selected from -SR7, -SOR7, -S02R7, and -S02NR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,- (Ci-c6) alkyl, -NR5R6, _〇R ", _ (C3-(: 7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 Substituted; R2 is-(C ^ -C6); and η is 1. The present invention also provides a compound represented by Formula 1, wherein Ri is -C02R] 2, -CONR5R6, -NHC0R12, -NR12CONR5R6, or -NR12S02R7, which is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(C "C6) alkyl, _ NR5R6, _0R12,-(C "c7) cycloalkyl,-(C2-C9) heterocyclyl, -C〇2R12, -CONR5r6, and -coNR5R8 are substituted; R2 is-(CVC6 ) Alkyl; and 11 is 1. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-((^-(: 6) alkyl, and it is optionally selected from hydrogen, halogen, hydroxyl, -N02, -CN, _ (CrC6) alkyl,-(C2-C6) alkenyl, _ (C2-C6) alkynyl, -C = N-OH, = fluorenyl), -NR5R6, -〇R12,-( C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -45- 200539871 (43) -CONR5R6, -CONR5R8, -SR7, -S〇R7, -S〇2R7,- S〇2NR5R6, _NHC〇R12, NR12c〇NR5R6, and -NR12S02R7 are substituted, wherein the-(C2-C6) alkenyl and-(C2_C6) alkynyl of the R2 group can be optionally passed through 1 to 3 Is substituted with an R "group; ... is, "" "alkyl; and η is 1. The present invention also provides a compound represented by formula 1, wherein R2 is _ (C3_C7) cycloalkyl or-((: 2_ <: 9) a heterocyclic group, which is optionally selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(CrCj alkyl,-(C2-c6) anhydroxyl,-( C2-C6) alkynyl, -c = N-OH, -C = N-0 ((C "C6) fluorenyl), -NR5R6, -OR ", _ (c 广 C7) cycloalkyl- (c Wide heterocyclyl, -C02R12, -CONR5R6, -CON R5R8, _sr7, _s〇r7, -S02R7, -S02NR5Re, -NHCOR12, -NR12CONR5R6, and -NR12s〇2R7 are substituted with groups of _ (C2-C6) alkenyl and-(C2_ ( : 6) an alkynyl group may be optionally substituted with 1 to 3 groups; ... is a (Ci " ~ C6) group; and η is 1. Another system of the present invention is a compound represented by formula i, Where R2 is -CO2. 2 and -CONr5R6, and they are arbitrarily selected via iS3 from hydrogen, halogen, hydroxyl, -no2, -CN,-(C ^ C6) alkyl,-(C2_C6) anhydroxyl,- (C2-C6) alkynyl-C = N-OH, _c = N-〇 ((Ci-y alkyl), _NR5R6, -〇R12,-(cfC7) cycloalkyl,-(C2-C9) hetero Ring group, -co2r12, one conr5r6, one conr5r8, one sr7, one sor7, _s〇2R7, -S02NR5R6, _nhc〇r12, _nr12c〇nr5r6, and one i2s〇2R7 group, among which (C "C6) alkenyl and mono (c" c6) alkynyl of the Kr2 group may be optionally substituted with 1 to 3 1 ^ 2 groups; alkyl-46-200539871 (44); and η is 1. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from hydrogen, hydroxyl, and-(C ^ Ce) alkyl, and it is optionally selected from hydrogen, halogen, hydroxyl,- CN,-(CrCe) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and a conr5r ^ group Substitution; R2 is hydrogen or mono (C "C6) alkyl, and it is optionally selected from 1 to 3 selected from hydrogen, halogen, hydroxy®, -N02, -CN,-(C" C6) alkyl,- (C2-C6) alkenyl,-(C2-C6) alkynyl, -C = N-OH, _C = N-〇 ((CrC6) alkyl), -NR5R6, -OR12,-(C3-C7) Cycloalkyl,-(C2-C9) heterocyclyl, -c〇2R12, -CONFER6, -CONR5R8, _sr7, _s〇r7, -s〇2r7, -S02NR5r6, _NHC〇R12, -NR12C〇NR5r6, and _ NR12S02R7 is substituted with a group in which-(c2-c6) alkenyl and-(c2-c6) alkynyl of the R2 group may be optionally substituted with 1 to 3 R12 groups; and η is 1. g The present invention also provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of hydrogen, hydroxyl, and -alkyl, and it is optionally selected from hydrogen, halogen, and hydroxyl through 1 to 3, respectively. -CN,-(C ^ U alkyl, -NR5R6, -〇R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -c〇2R] 2, -CONR5R6, and- Substituted by a group of CONR5R8; r2 is gas; and n is 10; the present invention also provides a compound represented by formula 1, wherein R1 is-(C! -C6) alkyl, and it is optionally substituted by 1 to 3 Selected from the group consisting of hydrogen, halogen, hydroxyl, -CN,-(Ci-Ce) group, -NR5R6, -〇R ", _ (c3-C7) ring group,-(C2-C9) heterocyclic group,- C02R] 2, -COON5R6, and -47-200539871 (45) substituted by -COON5R8; R2 is hydrogen; and n is 1. The present invention also provides a compound represented by Formula 1, wherein Ri Is selected from-(CrC7) cycloalkyl and-(C2_C9) heterocyclyl, and it is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN,-(c ^ -Ce) alkyl,- NR5R6, -ORl2,-(c3-匸 7) cycloalkyl,-(C2-C9) heterocyclyl, -c0r ", -CONR5R6, and -c0nr5r8 are substituted; r2 is hydrogen; And 11 is 10. The present invention also includes a compound represented by Formula 1, wherein R1 is selected from the group consisting of 10 (^ M6) alkyl, -0 (C3-C7) cycloalkyl, and -〇 (C2-C9 )miscellaneous And it is optionally selected from 1 to 3 by hydrogen, halogen, hydroxyl, -c N,-(CrCd alkyl, _NR5R6, -OR12, _ (C3-C7) cycloalkyl,-(C2-C9 ) Substituted with a heterocyclyl, -CO2R12, -CONR5R6, and -CONR5R8; R2 is hydrogen; and n is 1. One system of the present invention is a compound represented by Formula 1, wherein R1 is a NR5R6, and it is optionally selected from 1S3 by chlorine, halogen, via group-, -CN,-(C "C6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and a CONW group; R2 is hydrogen; and 11 is 1. Another system of the present invention is a compound represented by Formula 1, wherein R1 is selected from the group consisting of -SR7, -SOR7, -S02R7, and -S02NR5R6, and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, and hydroxyl, respectively. , -CN,-(C ^ Ce) alkyl, -NR5R6, -OR ",-(c3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and- Substituted by a group of CONR5R8; R2 is hydrogen; and n is 1. -48- 200539871 (46) The present invention also provides a compound represented by formula 1, wherein R1 is -CO2R12, -CONR5R6, -NHCOR12, _NR12C 〇NR5r6, or _NR12S02R7, and it is arbitrarily selected! To 3 are selected from hydrogen, halogen, hydroxyl, -CN,-(C "C6) alkyl, -NR5R6, -OR12,-(C3-C7) ring Alkyl, mono (C2-C9) heterocyclyl, one Co2R12, one CONR5R6, Hekou A group substituted by CONR5R8; R2 is hydrogen; and η is 1. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-(C ^ Ce) alkyl, and it is optionally passed through to 3 are selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(CrCj alkyl,-(C2-C6) alkenyl,-(c2-C6) alkynyl, -C = N-OH, -C = N-0 (((^-(^) alkyl), -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(c2-C9) heterocyclyl, -C02R12, -CONR5r6, -One of 〇NR5R8, one of SR7, _S〇R7, one of S02R7, -S02NR5R6, -NHCOR12, -NR12CONR5R6, and -NR12S02R7

基團所取代，其中該R2基團之-(C2 —C6)烯基和_(C2_C6)炔 基可任意地經1至3個Ri2基團所取代；R1是氫；及^是1。 本發明亦提供一種式1所示之化合物，其中 C：7)環烷基或-（C^C：9)雜環基，而其任意地經丨至3個分別選 自氫、鹵素、翔基、-N02、-CN、一（Cl-c6)烷基、一（c「 c6)嫌基、-（C2-C6)炔基、_c = N-〇H、_C = N - 〇((c「C6)焼 基)、一 NR5r6、— OR”、一r甘 / 广 (c3 C7)環烷基、-(c2-c；9)雜環基 、-C02R12、-CONR5R6、一 c〇nr5r8 …sr7、一 s〇r7、 - so2r7、-so2nr5r6、~nhcor12、一 nr12c〇nr5r6、和 - nr12s〇2R7之基團所取代，其中該R2基團之—（C2_C6)烯基 和-(q-C：6)炔基可任意地經1至3個1^2基團所取代；R1是氫 -49- 200539871 (47) ;及η是1。 本發明之另一體系是一種式1所示之化合物，其中R2 是-COJ12和- CONR5R6，而其任意地經個分別選自氫 、鹵素、羥基、-N02、_CN、-(CrCV 烷基、-(C2_C6)烯 基、-（c2-c6)炔基、-c = N- 〇H、-C = N- 院基）、 _NR5R6、—0R12、—（C3-C7)環烷基、-(C2-C9)雜環基、 一 C〇2R12、一 CONR5R6、一c〇NR5R8、一 SR7、一 SOR7、一 S02R7 -S02NR5R6^ -NHCOR12' -NR12CONRsR6' in-NR12S02R7 之基團所取代，其中該R2基團之-（C2-C6)烯基和-(C2-C6) 炔基可任意地經1至3個R12基團所取代；R1是氣；及η是1 〇 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、經基、和-（Ci-Ce)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、烷基、-NR5R6、-OR12 、-（c3-c7)環烷基、-(C2-C9)雜環基、-c〇2R12、 _ —CONR5R6、和-CONR5R8之基團所取代；r2是氫或_(Ci_ C6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-N02、- CN、-（C「C6)烷基、-（C「C6)烯基、-（C「C6)炔 基、_C = N_0H、_ON-0((C 广C6)烷基）、-NR5R6、-OR12 、-(C3_C7)環烷基、-（C2-C9)雜環基、-C02R】2、 一 CONR5R6、—C〇NR5R8、_SR7、—S〇r7、一 s〇2R7、 -S02NR5R6 ^ -NHCOR12 ' -NR12CONR5R6 ^ ^〇-NR12S02R7^ 基團所取代，其中該R2基團之-(C2-C6)烯基和-（C2-C6)炔 基可任意地經1至3個R12基團所取代；及11是2。 -50- 200539871 (48) 本發明亦提供一種式1所示之化合物，其中R1是選自 氫、羥基、和-(C^Ce)烷基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-CN、-（C^-Ce)烷基、-NR5R6、-〇R12 、-(C3_C7)環烷基、-(C2-C9)雜環基、-C02R12、 - CONR5R6、和-CONR5R8之基團所取代；R2是-(。「(^烷 基；及η是2。 本發明亦提供一種式1所示之化合物，其中R1是-（Cr Φ C 6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-（C】- C6)烷基、-NR5R6、- OR"、_(C「C7)環烷基 、一（C2 — C9)雜環基、-C02R12、一CONR5R6、和一c〇NR5R8之 基團所取代；R2是-(C^-Ce)烷基；及n是2。 本發明亦提供一種式1所示之化合物，其中R1是選自 一（CfC7)環烷基和-(C2-C9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、-CN、-(CrC6)焼基、-NR5R6 、-OR12、_(C3_C7)環烷基、-（C2-C9)雜環基一c〇2r”、 _ 一 c〇NR5R6、和-CONR5R8之基團所取代；r2 是 _(Ci_C6)烷 基；及η是2。 本發明亦包含一種式1所示之化合物，其中Ri是選自 一0(1-c6)烷基、-〇(c3-C7)環烷基、和_〇(CrC9)雜環基 ’而其任意地經1至3個分別選自氫、鹵素、羥基、-CN 、一（Ci-C6)烷基、-NR5R6、-OR12、-(CfC7)環烷基、 -（C2~C9)雜環基、-C〇2R12、- C〇NR5R6、和-c〇NR5R8 之基 團所取代；R2是-(C^CJ烷基；及η是2。 本發明之一體系是一種式1所示之化合物，其中Ri是 -51 - 200539871 (49) -NR5R6，而其任意地經1至3個分別選自氫、議素、經基 、-CN、-（CrC6)烷基、-NR5R6、-OR12、-（c3〜C7)環烷基 、-(C2 - C9)雜環基、-C〇2R12、—CONR5R6、和—c〇nr5r82 基團所取代；R2是_(Κ6)烷基；及11是2。 本發明之另一體系是一種式1所示之化合物，其中Rl 是選自-SR7、-S〇R7、-S02R7、和-S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-(Ci —c6)焼基 、-NR5R6、-0R12、-(C3-c7)環烷基、-(C2 一 C9)雜環基、 -C02RU、-C〇NR5r6、和一 c〇nr5r8 之基團所取代；r2 是 -（<^-(：6)烷基；及！!是 2。 本發明亦提供一種式1所示之化合物，其中Ri是 -C02R"、一c〇NR5R6、-NHC0R12、-NR12CONR5R6、或 一 NR12S02R7，而其任意地經1至3個分別選自氫、鹵素、經 基、-CN、-(CrCe)烷基、-NR5R6、_0R12、-（C3-C7)環烷 基、-(C2-C9)雜環基、_C02R12、- CONR5R6、和一 CONR5R8 之基團所取代；R2是-(C^Cd烷基；及η是2。 本發明亦提供一種式1所示之化合物，其中R2是氫或 一烷基，而其任意地經丨至3個分別選自氫、鹵素、 羥基、-N〇2、-CN、-(C!-C6)烷基、-(C2-C6)烯基、-(C2-C6)炔基、一 C = N一〇H、-C = n_〇（（Ci_c6)院基）、_NR5R6、 -OR12、一（c3-c7)環院基、一（c2-c9)雜環基、-co2r12、 -CONR5R6、一 c〇nr5r8、一sr7、一 s〇r7、一s〇2R7、 一 S〇2NR5R6、—nhc〇r12、_nr12c〇nr5r6、和 _nr12S〇2r72 基團所取代，其中該R2基團之-(c2-c6)烯基和-(c2_c6)炔 -52- 200539871 (50) 基可任意地經1至3個R12基團所取代；…是―（C1 — C6)烷基； 及η是2。 本發明亦提供一種式1所示之化合物，其中R2是—（c厂 cT)環烷基或-(q-C9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-no2、-CN、—（Ci-c6)烷基、-(C2一 c6)嫌基、-（C2-C6)炔基、一c = N-〇H、-CUGCrCe)院 基）、-NR5R6、-〇R12、-(c3-C7)環烷基、-(CfCj 雜環基 、-C02R12、- CONR5R6、一 CONR5R8、一 SR7、-SOR7、 - S02R7、-S02NR5R6、- NHCOR12、- NR12CONR5R6、和 - nr12s〇2R7之基團所取代，其中該…基團之-(C2-C6)烯基 和-（Cq-C6)炔基可任意地經1至3個ri2基團所取代；…是 -（Q-C6)烷基；及n是2。 本發明之另一體系是一種式1所示之化合物，其中R2 是-C〇2R12和-c〇NR5R6，而其任意地經1至3個分別選自氫 、鹵素、羥基、-N02、-CN、-(C^Cd 烷基一（C2-C6)烯 基、-（C2-C6)炔基、-C = N-〇H、-ON-0((C「C6)烷基）、 -nr5r6、~〇ri2、—（C3_c7)環烷基、-(C2-c9)雜環基、 一 C〇2R12、一 CONR5R6、一C〇NR5R8、_SR7、一S〇R7、-S02R7 、-S02NR5R6 > -NHCOR12 ^ -NR12CONR5R6 ^ fn~NR12S02R7 之基團所取代，其中該r2基團之-(C2-C6)烯基和-(c2-c6) 炔基可任意地經1至3個R!2基團所取代；R1是烷基 ;及n是2。 本發明亦提供一種式1所示之化合物，其中R 1是選自 氫、經基、和烷基，而其任意地經1至3個分別選 -53- 200539871 (51) 自氫、_素、羥基、-CN、-(C!-C6)烷基、-NR5R6、-OR12 、-（C3-C7)環院基、-(C2 - C9)雜環基、-c〇2R12、 -CONR5R6、和-CONR5R8之基團所取代；r：^_(Ci_C6)院 基；及η是2。 本發明亦提供一種式1所示之化合物，其中Ri是—（Ci_ Ce)烷基’而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-（Ci-Ce)烷基、-NR5R6、-OR。、—（c^cj環烷基 、-(C2-C9)雜環基、-C〇2R12、-CONR5R6、和-c〇NR5R8 之 基團所取代；R2是-(C^-Ce)烷基；及n是2。 本發明亦提供一種式1所示之化合物，其中Rl是選自 -（CrC7)環烷基和-（C2-C9)雜環基，而其任意地經1至3個 分別選自氫、鹵素、羥基、-CN、-(C!-C6)烷基、-NR5R6 、-OR12、-(C3-C7)環烷基、-(C2-C9)雜環基、-c〇2R12、 -CONW、和 _c〇nr5r8$ 基團所取代；焼 基；及η是2。 本發明亦包含一種式1所示之化合物，其中Rl是選自 -〇(CrC6)烷基、-〇(C3-C7)環烷基、和-〇(c2-C9)雜環基 ，而其任意地經1至3個分別選自氫、鹵素、羥基、—CN 、一（CrCj 烷基、-NR5R6、-OR12、-(C3-C：7)環烷基、 一（c2-c9)雜環基、_C〇2R12、-CONR5R6、和一 c〇NR5R8 之基 圑所取代；R2是-(C^Cj烷基；及η是2。 本發明之一體系是一種式1所示之化合物，其中Ri是 一而其任意地經1至3個分別選自氫、鹵素、經基 、-CN、-(C】-C6)烷基、_NR5R6、—〇Ri2、—（C3_C7)環烷基 -54- 200539871 (52) 、—（C2~C9)雜環基、-C〇2R12、一C〇NR5R6、和一 C〇NR5R8 之 基團所取代；R2是-(C^CJ烷基；及η是2。 本發明之另一體系是一種式1所示之化合物，其中R1 是選自-SR7、-SOR7、-S02R7、和- S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-(C^Ce)烷基 、-NR5R6、-or”、-(C3_c7)環烷基、-(C2-C9)雜環基、 一 C〇2R12、一CONR5R6、和-CONR5R8之基團所取代；R2是 -（Κ6)焼基；及η是2。 本發明亦提供一種式1所示之化合物，其中R1是 -C02R"、-CONR5R6、-NHC0R12、-NR12CONR5R6、或 -NR12S02R7，而其任意地經1至3個分SU選自氫、鹵素、羥 基、-CN、—（Ci-c6)烷基、-Nr5R6、一 〇Rl2、一(C3_c7)環烷 基、-（C2-C9)雜環基、-C02R12、-CONR5R6、和-CONR5R8 之基團所取代；R2是-(C^CJ烷基；及η是2。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -(Ci-Cd烷基，而其任意地經1至3個分別選自氫、鹵素、 經基、-N〇2、-CN、-(CrC6)烷基、_(C2-C6)烯基、-(C2-c6l·炔基、一C = N-〇H、一C = N 一〇（（Ci 一 C6)院基）、_nr5r6、 -0r12、-(C3-C7)環烷基、-(C2_C9)雜環基、_c〇2r12、 - CONr5r6、-C〇NR5R8、- SR7、- S0R7、- S02R7、 一 S〇2NR5R6、一 NHC0R12、一 NR12C〇NR5R6、和 _NR12S〇2R7 之 基團所取代，其中該R2基團之-(c2-c6)烯基和-(C2-C6；^ 基可任意地經1至3個基團所取代；1^是-((：1-〇：6)烷基； 及η是2。 -55- 200539871 (53) 本發明亦提供一種式i所示之化合物，其中R2是—（(：3一 C7)環垸基或-（C2_C9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-N02、- CN、-（C「C6)烷基、-(C2-C6)烯基、_(C2-C6)炔基、—c = N-〇H、—C = N-0((c「c6m 基）、-NR5R6、-OR"、_(C3_C7)環烷基一（c广cj 雜環基 、-C〇2R12、- CONR5R6、一 C〇NR5R8、_SR7、一 S〇R7、 - S02R7、-S02NR5R6、-NHCOR12、- NR12CONR5R6、和 -NR12S〇2R7之基團所取代，其中該…基團之-(C2-C6)烯基 和-（CfC：6)炔基可任意地經1至3個1^2基團所取代；…是 一（C^Ce)烷基；及η是2。 本發明之另一體系是一種式i所示之化合物，其中R2 是-C02R12和-c〇NR5R6，而其任意地經1至3個分別選自氫 、鹵素、羥基、-no2、-CN、一（Ci-C6)烷基、一（C2_C6)烯 基、-（c2-c6)炔基、-c = N - 0H、- C = N-OGCrCj 烷基）、 - NR5R6、-OR”、_(c3 —c7)環烷基、_(C「C9)雜環基、 一 C〇2R12、—CONR5R6、 -c〇NR5R8 ' - SR7、—S〇R7、_s〇2r7 、-S02NR5R6、-NHCOr12、-nr”c〇nr5r6、和一 nr12s〇2r7 之基團所取代，其中該R2基團之~(c2-c6)烯基和-(c2-c6) 炔基可任意地經1至3個R12基團所取代；N是—（Ci —c6)烷基 :及η是2。 本發明亦提供一種式1所示之化合物，其中Ri是選自 氯、經基、和-(CrCd烷基，而其任意地經1至3個分別選 自氫、幽素、羥基、-CN、-(C广C6)烷基、-NR5R6、-OR12 、-（C3 - C7)環院基、—（c2-C9)雜環基、—c〇2R12、 56- 200539871 (54) -CONR5R6、和-CONR5R8之基團所取代；r2是氫或-(Ci_ C 6)烷基，而其任意地經1至3個分別選自氫、鹵素、羥基 、-N02、-CN、-(C厂C6)烷基、-(C2 —C6)烯基、-(C2-C6)炔 基、_C = N — 〇H、一C二N — 〇（（C广C6)烷基）、-NR5R6、-〇r12 、-（C3-C7)環烷基、-（C2-C9)雜環基、—c〇2r”、 一 CONR5R6、—CONR5r8、_sr7、_s〇r7、一s〇2R7、 - S02NR5R6、-NHCOR12、- NR12CONR5R6、和-NR12S02R7 之 B基團所取代，其中該R2基圑之-(C2-C6)烯基和-(C2-C6)炔 基可任意地經1至3個R 12基團所取代；及^是2。 本發明亦提供一種式1所示之化合物，其中Ri是選自 氫、經基、和-(C广C6)烷基，而其任意地經1至3個分別選 自氣、鹵素、羥基、-CN、烷基、-NR5R6、- OR12 、-(C3-C7)環院基、-（C2-C9)雜環基、-c〇2R12、 - CONW、和-CONr5r8之基圑所取代；r2是氫；及 〇 & 本發明亦提供一種式1所示之化合物，其中Ri是_(Cl-Is substituted with a group in which-(C2-C6) alkenyl and _ (C2-C6) alkynyl of the R2 group may be optionally substituted with 1 to 3 Ri2 groups; R1 is hydrogen; and ^ is 1. The present invention also provides a compound represented by Formula 1, wherein C: 7) cycloalkyl or-(C ^ C: 9) heterocyclyl, which is optionally selected from hydrogen, halogen, and , -N02, -CN, mono (Cl-c6) alkyl, mono (c "c6) alkyl,-(C2-C6) alkynyl, _c = N-〇H, _C = N-〇 ((c "C6) fluorenyl), -NR5r6, -OR", -r-glycan / c (C3 C7) cycloalkyl,-(c2-c; 9) heterocyclyl, -C02R12, -CONR5R6, -connr5r8 ... sr7, a sor7,-so2r7, -so2nr5r6, ~ nhcor12, an nr12c〇nr5r6, and-nr12s〇2R7 are substituted, wherein the R2 group is-(C2_C6) alkenyl and-(qC: 6 ) The alkynyl group may be optionally substituted with 1 to 3 1 ^ 2 groups; R1 is hydrogen-49-200539871 (47); and η is 1. Another system of the present invention is a compound represented by Formula 1, wherein R2 is -COJ12 and -CONR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(CrCV alkyl, -(C2_C6) alkenyl,-(c2-c6) alkynyl, -c = N-OH, -C = N-coated), _NR5R6, -0R12,-(C3-C7) cycloalkyl,-( C2-C9) Heterocyclyl, one Co2R12, one CONR5R6, one coNR5R8, one SR7, one SOR7, one S02R7 -S02NR5R6 ^ -NHCOR12 '-NR12CONRsR6' in-NR12S02R7, where R2 The-(C2-C6) alkenyl and-(C2-C6) alkynyl groups of the group may be optionally substituted with 1 to 3 R12 groups; R1 is a gas; and η is 1. The present invention also provides a formula 1 The compound shown, wherein R1 is selected from the group consisting of hydrogen, meridian, and-(Ci-Ce) alkyl, and it is optionally selected from one to three selected from hydrogen, halogen, hydroxyl, -CN, alkyl,- NR5R6, -OR12,-(c3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -c02R12, _-CONR5R6, and -CONR5R8 are substituted; r2 is hydrogen or _ (Ci_ C6) alkyl, which is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -N02, -CN,-(C "C6 ) Alkyl,-(C "C6) alkenyl,-(C" C6) alkynyl, _C = N_0H, _ON-0 ((C-C6) alkyl), -NR5R6, -OR12,-(C3_C7) ring Alkyl,-(C2-C9) heterocyclyl, -C02R] 2, -CONR5R6, -CONR5R8, _SR7, -Sor7, -s02R7, -S02NR5R6 ^ -NHCOR12 '-NR12CONR5R6 ^ ^ 〇- NR12S02R7 ^ group, wherein-(C2-C6) alkenyl and-(C2-C6) alkynyl of the R2 group can be optionally substituted with 1 to 3 R12 groups; and 11 is 2.- 50-200539871 (48) The present invention also provides a compound represented by Formula 1, wherein R1 is selected from hydrogen, hydroxyl, and-(C ^ Ce) alkyl, and is optionally selected from hydrogen through 1 to 3 , Halogen, hydroxy, -CN,-(C ^ -Ce) alkyl, -NR5R6, -〇R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 is substituted by a group; R2 is-(. "(^ Alkyl; and η is 2. The present invention also provides a compound represented by formula 1, wherein R1 is-(Cr Φ C 6) alkyl, and It is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN,-(C) -C6) alkyl, -NR5R6, -OR ", _ (C 「C7) cycloalkyl, and (C2C9) heterocyclyl, -C02R12, a CONR5R6, and a group of c〇NR5R8 substituted; R2 is - (C ^ -Ce) alkyl; and n is 2. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from the group consisting of mono (CfC7) cycloalkyl and-(C2-C9) heterocyclyl, and it is optionally selected from hydrogen and halogen through 1 to 3 , Hydroxy, -CN,-(CrC6) fluorenyl, -NR5R6, -OR12, _ (C3_C7) cycloalkyl,-(C2-C9) heterocyclyl-co2r ", _-coon5R6, and- Substituted by a group of CONR5R8; r2 is a _ (Ci_C6) alkyl group; and η is 2. The present invention also includes a compound represented by Formula 1, wherein Ri is selected from a 0 (1-c6) alkyl group,-. (c3-C7) cycloalkyl, and _〇 (CrC9) heterocyclyl ', which are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN, mono (Ci-C6) alkyl,- NR5R6, -OR12,-(CfC7) cycloalkyl,-(C2 ~ C9) heterocyclyl, -CO2R12, -CONR5R6, and -coNR5R8 are substituted; R2 is-(C ^ CJ alkyl; and η is 2. One system of the present invention is a compound represented by Formula 1, wherein Ri is -51-200539871 (49)-NR5R6, and it is optionally selected from hydrogen, Protoxin, meridian, -CN,-(CrC6) alkyl, -NR5R6, -OR12,-(c3 ~ C7) cycloalkyl,-(C2-C9) heterocyclyl, -C〇2R12, -CO NR5R6, and -connr5r82 groups are substituted; R2 is _ (Κ6) alkyl; and 11 is 2. Another system of the present invention is a compound represented by formula 1, wherein R1 is selected from -SR7,- S〇R7, -S02R7, and -S02NR5R6, which are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(Ci -c6) fluorenyl, -NR5R6, -0R12,-(C3 -c7) cycloalkyl,-(C2 -C9) heterocyclyl, -C02RU, -CONR5r6, and -conn5r8; r2 is-(< ^-(: 6) alkyl And !! is 2. The present invention also provides a compound represented by Formula 1, wherein Ri is -C02R ", -coNR5R6, -NHC0R12, -NR12CONR5R6, or -NR12S02R7, and optionally by 1 to 3 Selected from hydrogen, halogen, meridian, -CN,-(CrCe) alkyl, -NR5R6, _0R12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, And a group substituted with CONR5R8; R2 is-(C ^ Cd alkyl; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or an alkyl group, and optionally丨 to 3 are selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(C! -C6) alkyl -(C2-C6) alkenyl,-(C2-C6) alkynyl, -C = N-〇H, -C = n_〇 ((Ci_c6) courtyard), _NR5R6, -OR12, one (c3-c7 ) Cyclocyclyl, one (c2-c9) heterocyclyl, -co2r12, -CONR5R6, one cOnr5r8, one sr7, one so7, one so2R7, one so2NR5R6, -nhc〇r12, _nr12c 〇nr5r6, and _nr12S〇2r72 groups, wherein the-(c2-c6) alkenyl and-(c2_c6) alkyn-52- 200539871 (50) groups of the R2 group can be optionally passed through 1 to 3 R12 Is substituted by a group; ... is-(C1-C6) alkyl; and n is 2. The present invention also provides a compound represented by Formula 1, wherein R2 is-(c factory cT) cycloalkyl or-(q-C9) heterocyclyl, and it is optionally selected from hydrogen and halogen through 1 to 3 , Hydroxy, -no2, -CN,-(Ci-c6) alkyl,-(C2-c6) alkyl,-(C2-C6) alkynyl, -c = N-〇H, -CUGCrCe) , -NR5R6, -〇R12,-(c3-C7) cycloalkyl,-(CfCj heterocyclyl, -C02R12, -CONR5R6, -CONR5R8, -SR7, -SOR7,-S02R7, -S02NR5R6,-NHCOR12,- NR12CONR5R6, and-nr12s〇2R7 are substituted, wherein the-(C2-C6) alkenyl and-(Cq-C6) alkynyl of the ... group may be optionally substituted with 1 to 3 ri2 groups; ... is-(Q-C6) alkyl; and n is 2. Another system of the present invention is a compound represented by Formula 1, wherein R2 is -C〇2R12 and -coNR5R6, and it is optionally To 3 are selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(C ^ Cd alkyl- (C2-C6) alkenyl,-(C2-C6) alkynyl, -C = N-OH -ON-0 ((C "C6) alkyl), -nr5r6, ~ 〇ri2,-(C3_c7) cycloalkyl,-(C2-c9) heterocyclyl, -C02R12, -CONR5R6, -C 〇NR5R8, _SR7, S〇R7, -S02R7, -S02NR5R6 > -NHCOR12 ^ -NR12CONR5R6 ^ fn ~ NR12S02R7 are substituted with the-(C2-C6) alkenyl and-(c2-c6) alkynyl of the r2 group Optionally substituted with 1 to 3 R! 2 groups; R1 is an alkyl group; and n is 2. The present invention also provides a compound represented by formula 1, wherein R1 is selected from the group consisting of hydrogen, aridyl, and alkane And it is arbitrarily selected by one to three -53- 200539871 (51) from hydrogen, _ prime, hydroxyl, -CN,-(C! -C6) alkyl, -NR5R6, -OR12,-(C3 -C7) Cyclocyclyl,-(C2-C9) heterocyclyl, -co2R12, -CONR5R6, and -CONR5R8 are substituted by groups; r: (Ci_C6) cyclyl; and η is 2. The invention also provides a compound represented by Formula 1, wherein Ri is-(Ci_Ce) alkyl 'and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(Ci-Ce) alkane through 1 to 3, respectively. , -NR5R6, -OR.,-(C ^ cj cycloalkyl,-(C2-C9) heterocyclyl, -CO2R12, -CONR5R6, and -coNR5R8 groups; R2 is- (C ^ -Ce) alkyl; and n is 2. The present invention also provides a compound represented by Formula 1, wherein R1 is selected from-(CrC7) cycloalkyl and-(C2-C9) heterocyclyl, and it is optionally selected from hydrogen and halogen via 1 to 3 , Hydroxyl, -CN,-(C! -C6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -c〇2R12, -CONW, And —conn5r8 $ groups; fluorenyl; and n is 2. The present invention also includes a compound represented by Formula 1, wherein R1 is selected from the group consisting of -0 (CrC6) alkyl, -0 (C3-C7) cycloalkyl, and -0 (c2-C9) heterocyclyl, and Arbitrarily selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN, mono (CrCj alkyl, -NR5R6, -OR12,-(C3-C: 7) cycloalkyl, mono (c2-c9) hetero A cyclic group, —CO2R12, —CONR5R6, and —co—NR5R8 — substituted by R; R2 is — (C ^ Cj alkyl; and η is 2. One system of the present invention is a compound represented by Formula 1, Wherein Ri is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, meridian, -CN,-(C) -C6) alkyl, _NR5R6, -〇Ri2,-(C3_C7) cycloalkyl- 54-200539871 (52),-(C2 ~ C9) heterocyclyl, -CO2R12, -CONR5R6, and -CONR5R8 are substituted; R2 is-(C ^ CJ alkyl; and η Yes 2. Another system of the present invention is a compound represented by Formula 1, wherein R1 is selected from the group consisting of -SR7, -SOR7, -S02R7, and -S02NR5R6, and is optionally selected from hydrogen, Halogen, hydroxy, -CN,-(C ^ Ce) alkyl, -NR5R6, -or ",-(C3_c7) cycloalkyl,-(C2-C9) heterocyclyl, -C 〇2R12, a CONR5R6, and -CONR5R8 are substituted; R2 is-(Κ6) fluorenyl; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R1 is -C02R ", -CONR5R6 , -NHC0R12, -NR12CONR5R6, or -NR12S02R7, which is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(Ci-c6) alkyl, -Nr5R6, -0Rl2,- (C3_c7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 are substituted; R2 is-(C ^ CJ alkyl; and η is 2. The present invention also Provided is a compound represented by Formula 1, wherein R2 is hydrogen or-(Ci-Cd alkyl, and it is optionally selected from hydrogen, halogen, halogen, -N02, -CN,- (CrC6) alkyl, _ (C2-C6) alkenyl,-(C2-c6l · alkynyl, -C = N-OH, -C = N-10 ((Ci-C6) alkenyl), _nr5r6, -0r12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -c〇2r12, -CONr5r6, -C〇NR5R8, -SR7, -S0R7, -S02R7, -S02NR5R6, -NHC0R12, NR12C〇NR5R6 and _NR12S〇2R7 are substituted, wherein the-(c2-c6) alkenyl and-(C2-C6; It may be optionally substituted with 1 to 3 groups; ^ is 1 - ((: 1- ○: 6) alkyl; and η 2. -55- 200539871 (53) The present invention also provides a compound represented by formula i, wherein R2 is — ((: 3—C7) cyclofluorenyl or — (C2_C9) heterocyclyl, and it is optionally passed through 1 to 3 Each selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(C "C6) alkyl,-(C2-C6) alkenyl, _ (C2-C6) alkynyl, -c = N-〇H , —C = N-0 ((c "c6m group), -NR5R6, -OR ", _ (C3_C7) cycloalkyl- (c-cj heterocyclic group, -C〇2R12,-CONR5R6,-CONR5R8 , _SR7, -SOR7, -S02R7, -S02NR5R6, -NHCOR12, -NR12CONR5R6, and -NR12S〇2R7 are substituted by the groups in which-(C2-C6) alkenyl and-(CfC: 6) The alkynyl group may be optionally substituted with 1 to 3 1 ^ 2 groups; ... is a (C ^ Ce) alkyl group; and η is 2. Another system of the present invention is a compound represented by formula i Where R2 is -C02R12 and -coNR5R6, and it is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -no2, -CN, mono (Ci-C6) alkyl, and mono (C2_C6) ene ,-(C2-c6) alkynyl, -c = N-0H, -C = N-OGCrCj alkyl),-NR5R6, -OR ", _ (c3 -c7) cycloalkyl, _ (C「 C9 ) Heterocyclyl, one Co2R12, -CONR5R6, -coon5R8 '-SR7, -SOR7, _s〇2r7, -S02NR5R6, -NHCOr12, -nr "coonr5r6, and a nr12s〇2r7 group, where this ~ (C2-c6) alkenyl and-(c2-c6) alkynyl of R2 group may be optionally substituted by 1 to 3 R12 groups; N is-(Ci -c6) alkyl: and η is 2 The present invention also provides a compound represented by Formula 1, wherein Ri is selected from the group consisting of chloro, meridian, and-(CrCd alkyl, and is optionally selected from hydrogen, peptidyl, hydroxy,- CN,-(C-C6) alkyl, -NR5R6, -OR12,-(C3-C7) ring courtyard group,-(c2-C9) heterocyclic group, -c〇2R12, 56- 200539871 (54) -CONR5R6 , And -CONR5R8 are substituted; r2 is hydrogen or-(Ci_C 6) alkyl, which is optionally selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(C Plant C6) alkyl,-(C2-C6) alkenyl,-(C2-C6) alkynyl, _C = N-oH, one-C-di-N-o ((C-C6) alkyl), -NR5R6, -〇r12,-(C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -c〇2r ", -CONR5R6, -CONR5r8, _sr7, _s〇r7, -s02R7,-S02NR5R6, -NHCOR12 -NR12CONR5R6 and -NR12S02R7 are substituted by the B group, wherein the R2 group-(C2-C6) alkenyl and-(C2-C6) alkynyl can be optionally substituted with 1 to 3 R 12 groups ; And ^ is 2. The present invention also provides a compound represented by Formula 1, wherein Ri is selected from the group consisting of hydrogen, meridian, and-(C-C6) alkyl, and it is optionally selected from the group consisting of gas, halogen, hydroxyl, -CN, alkyl, -NR5R6, -OR12,-(C3-C7) ring courtyard,-(C2-C9) heterocyclyl, -co2R12, -CONW, and -CONr5r8 are substituted by 圑; r2 Is hydrogen; and the present invention also provides a compound represented by Formula 1, wherein Ri is-(Cl-

Ce)院基’而其任意地經1至3個分別選自氫、鹵素、羥基 、一CN、-（Ci-c6)烷基、一 nr5r6、_〇R12、一（C「C7)環烷基 、-（c2-c9)雜環基、-C02R12、-CONR5R6、和 _CONR5R8 之 基團所取代；R2是氫；及η是2。 本發明亦提供一種式1所示之化合物，其中R1是選自 一⑴3-CJ環烷基和-(c2-c9)雜環基，而其任意地經1至3個 分別每自氫、鹵素、經基、-CN、-(C^-Ce)院基、-NR5R6 、-OR12 …（C3 —C7)環烷基、—（C2 —C9)雜環基、—c〇2R12、 ‘57· 200539871 (55) -CONW、和-COMR5R«之基團所取代；R2是氫；及〇是2 〇 本發明亦包含一種式1所不之化合物，其中是選自 -〇(CrC6)烷基、-0(C3-C7)環烷基、和-〇(C2_c9)雜環基 ’而其任意地經1至3個分別選自氫、鹵素、羥基、-CN 、-(c广C6)烷基、-NR5R6、-OR12、一（q —C7)環烷基、 -（c2- C9)雜環基、-C〇2R】2、-C〇NR5R6、和一c〇NR5R8之基 B 團所取代；R2是氫；及η是2。 本發明之一體系是一種式1所示之化合物，其中R1是 - NR5R6，而其任意地經1至3個分別選自氫、鹵素、羥基 、-CN、-（CrC6)烷基、-NR5R6、-〇R”、一（C「C7)環烷基 、-（c2 - c9)雜環基、-C02R12、- CONR5R6、和一 C〇NR5R8 之 基團所取代；R2是氫；及η是2。 本發明之另一體系是一種式1所示之化合物，其中R1 I 是選自-SR7、-SOR7、-S02R7、和- S02NR5R6，而其任意地 經1至3個分別選自氫、鹵素、羥基、-CN、-(Ci-Cj烷基 、-MW、—〇R"、-(ere?)環烷基、-(C2_c9)雜環基、 -C02R12、-CONR5R6、和-CONR5R8 之基團所取代；R2 是氫 ;及η是2。 本發明亦提供一種式1所示之化合物，其中R1是 -C02R"、一 CONW、-NHCOR】2、-NR】2C〇NR5r6、或 -NR12S02R7，而其任意地經1至3個分別選自氫、鹵素、羥 基、-CN、-(C】-C6)烷基、-NR5R6、- OR12、-(C3-C7)環烷 基、-（C2*»C9)雜環基、-C〇2R12、-CONR5R6、和-CONR5R8 -58- 200539871 (56) 之基團所取代；R2是氫；及η是2。 本發明亦提供一種式1所示之化合物，其中R2是氫或 -（C^CJ烷基，而其任意地經1至3個分別選自氫、鹵素、 經基、-N02、-CN、-（C^-Ce)院基、-（C2_C6)嫌基、_(C2 -C6)炔基、-C = N-〇H、-C = N-〇((C「C6)烷基）、-NR5R6、 -OR 、—（C3-C!7)環院基、-(C2-C9)雜環基、-C02R12、 一 CONR5R6、一 C〇NR5R8、-Sr7、—s〇r7、一s〇2R7、 - S02NR5R6、-NHCOR12、- NR12CONR5R6、和-NR12S02R7 之 基團所取代，其中該R2基團之-(C2-C6)烯基和—Ce)炔 基可任意地經1至3個RU基團所取代；是氫；及η是2。 本發明亦提供一種式1所示之化合物，其中R2是_(C3-CT)環院基或-(CfC：9)雜環基，而其任意地經1至3個分別選 自氫、鹵素、羥基、-N02、-CN、-（C^CJ烷基、-(C2-C6)嫌基、-（C2-C6)炔基、一c = N-〇H、-C = N-0(((^-(^6)垸 基）、-nr5r6、-or"、-(C3_C7)環烷基、_(C2 —Cs)雜環基 、-C02R12、-CONR5R6、一 c〇NR5R8、一 SR7、—s〇r7、 - S02R7、-S02NR5R6、~NHC0R12、-NR12CONR5R6、和 - NR12S〇2R7之基團所取代，其中該…基團之_(C2-C6)烯基 和-(q-C6)炔基可任意地經1至3個尺12基團所取代；Rl是氫 ;及η是2。 本發明之另一體系是一種式1所示之化合物，其中R2 是-C〇2R12和-CONR5R6，而其任意地經^至3個分別選自氫 、鹵素、羥基、-N〇2、— CN、-(Ci_C6)烷基、—（C2_C6)烯 基、_(C2-C6)炔基一c = N-〇H、_Ο.0((Κ6)烷基）、 -59- 200539871 (57) - NR5R6、-〇R12、-（C「C7)環烷基、-(c2-c9)雜環基、 —C〇2R12、-CONR5R6 ' 一CQNR5R8、-Sr7、_s〇R7、_5〇^7 、_s〇2nr5r6、一nhc〇r12、一NR12C〇NR5r6、禾口一nr12S〇2R7 之基團所取代，其中該R2基團之-（c2-c6)烯基和-(c2-c6) 炔基可任意地經1至3個R12基團所取代；R1是氫；及η是2 〇 本發明亦提供一種式1所示之化合物，其中R1和R2與 Β 相連接的原子一起形成_(C3_C1())環院基，而其任意地經1 至3個分別選自氫、鹵素、羥基、-N02、-CN、- (C「C6：) 院基、（C2~*C6)嫌基、-（C2-C6)快基、~c = N- 0H、-C = N*~ 0((C「C6)院基）、-NR5R6、- OR12、-（C3-C7)環院基、 _(C2~~C9)雜環基、一 C 〇 2 R 12、一 C 〇 N R 5 R6、— ◦〇 n R5 R8、- s R7 、一 SOR7、一s〇2R7、一s〇2NR5R6、-nhcoru、 -NR12CONR5R6、和-NRl2S〇2R7之基團所取代，其中該環狀 基團之-(CrC6)烯基和- (CrC6)炔基可任意地經1至3個 > 基團所取代。 本發明亦提供一種式1所示之化合物，其中…和…與 相連接的原子一起形成-(q-C9)雜環基，而其任意地經i 至3個分別選自氫、鹵素、羥基、-N〇2、—CN、— 院基、-（C 2 - c 6)嫌基、-（c 2 - C 6)炔基、-c =： N - ο Η、_ C = N _ 〇((c〗-c6)烷基）、—nr5r6、—ori2、-(C3_C7)環院基、 -（c2-c9)雜環基、一c〇2Rl2、-c〇NR5R6、〜c〇nr5r8、_sr7 、一S〇R7、一S〇2R7、__s〇2Nr5r6、-NHC〇r12、 -NR"CONR5R6、和-NR"s〇2R7之基團所取代，其中該環狀 -60- 200539871 (58) 基團之- (C2-C6)烯基和-(C2-C6)炔基可任意地經1至3個R12 基團所取代。 本發明亦提供一種式1所示之化合物，其中R1和R2與 相連接的原子一起形成-(C3-C1())環烷基，而其任意地經1 至3個分別選自氫、鹵素、羥基、-n〇2、-CN、-（C丨-C6) 垸基、-（C2_C6)烯基、-（C2-C6)炔基、-C = N- OH、- C = N -〇 ((C 1 - C 6)院基）、-N R5 R6、- 〇 R 12、- (C 3 - C 7)環院基、 ® _(C2-C9)雜環基、一C〇2R12、_C〇NR5r6、-C〇NR5R8、_SR7 、-SOR7、一 s〇2R7、_S02NR5R6、一 NHC0Ri2、 - NR12C〇NR5R6、和-NR12S02R7之基團所取代，其中該環狀 基團之-（C2_C6)烯基和- (c2_c6)炔基可任意地經1至3個R12 基團所取代；及η是1。 本發明亦提供一種式1所示之化合物，其中R1和R2與 相連接的原子一起形成-(G2 - C $)雜環基，而其任意地經1 至3個分別選自氫、鹵素、羥基、-Ν02、-CN、-（C^-Ce) 院基、-（C2-C6)嫌基、_(C2_C6)炔基、-C = N - OH、-C = N_ 〇((Κ6)烷基）、-NR5R6、- OR12、-（C3-C7)環院基、 -（c2-c9)雜環基、_co2r12、_c〇nr5r6、一conr5r8、一sr7 、-SOR7、- S02R7、- S02NR5R6、- NHCOR12、 一 NR12C〇NR5R6、和一 NR12so2R7之基團所取代，其中該環狀 基團之~*(C2_C6)嫌基和-（C2"~C6)快基可任意地經1至3個R12 基團所取代；及η是1。 於一較佳體系中，R4是選自氫、-(C!-C6)院基、_(c「 C7)環烷基和-(CfC9)雜環基之取代基；其中該y取代基 -61 - 200539871 (59) 之-（CrC6)烷基、-(c3 地經1至3個分別選自氫 -CN、-NR5R6、-OR12、 、-C02R12、和-CONR5 述R4取代基之雜原子不 -c7)環烷基和- (c2-c9)雜環基任意 、鹵素、經基、-(C1_C6)院基、 -（c3-c7)環烷基、-（c2-c9)雜環基 R8之基團所取代：其先決條件是上 可與鍵結至另一雜原子的SP 3碳原 子相鍵結；及其中該-C〇NR5R8中之R5和R8可與相連結的 原子一起形成-（C3-CI())環焼基或_(C2-c9)雜環基。 於另一較佳體系中，R4是氫。 另外，本發明提供一種式1所示之化合物，其中R5和 R6各是分別選自氫和烷基之取代基，而其任意地 經上述基團所取代。 本發明之特殊體系是選自下列之化合物： 1^-（1-甲基-1-苯基-乙基）-3-{[2-(2-酮-23 —二氫_1心 D引Π朵-5-基胺基）-5-三氟甲基—嘧啶基胺基]—甲基卜苯磺 醯胺； 3-{[2 -（2-酮-2,3一二氫—1H-吲哚-5一基胺基）一5一三氟甲 基-嘧啶-4-基胺基]-甲基卜苯磺醣胺； 5-{4-[3-(三氟甲磺醯基）—苯甲胺基]三氟甲基—嘧 啶-2 -基胺基卜1,3 -二氫-吲哚-2-酮； 5-{4_ [(哌啶-3-基甲基卜胺基]一5一三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(卜甲磺醯基-哌啶_3_基甲基）—胺基卜5_三氟甲 基-嘧啶-2-基胺基卜^-二氫-吲哚酮； N -（3-U2-(2_ 酮- 2,3-二氫-1H-吲哚-5-基胺基）_5-三 -62- 200539871 (60) 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； 3 -酮- 3- (3-{[2-(2-酮-2,3_ 二氫-1H -卩引 D朵-5-基胺基）_ 5-三氟甲基-嘧啶-4-基胺基]-甲基卜哌啶-1-基）-丙腈； 5-{4-[3-(1，1-二嗣-1N6-異噻哗院-2-基）-丙胺基]-5-三氟甲基-嘧陡-2-基胺基卜1,3-二氫-卩引卩朵-2-酮； 5 - [4-(2-甲基-丁胺基）-5-三氟甲基-赔Π定-2-基胺基]-1，3 -二氫-D引D朵-2 -酮； 5 - {4-[(1_甲磺醯基-丨根卩定-2-基甲基）-胺基]-5-三氟甲 基-喃Π定-2-基胺基}-1，3_二氫-巧丨D朵-2 -酮； N - {2-[2-(2 -酮-2,3 -二氫-1H-B 引 D朵 _5_基胺基）-5_ 三 氟甲基-嘧啶-4-基胺基]-乙基}-甲磺醯胺； N-{4_[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-丁基卜甲磺醯胺； 5 - {4-[(1_甲磺醯基-呢陡-4-基甲基）-胺基]-5_三氟甲 基-喃Π定-2-基胺基卜1,3 -二氫-D引Π朵-2-酮； N- 甲基- N- {2 - [2-(2 -酮-2,3-二氫-1H-D 引 D朵-5-基胺基 )_5_三氟甲基-喷陡-4 -基胺基]-乙基卜甲擴酸胺； 甲磺酸3-{[2-(2-酮-2,3 -二氫-1H-D引B朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-苯酯； N - {3-[2-(2_ 酮-2,3 -二氫-1H-D 引 D朵-5-基胺基）_5- 三 氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5-{4-[(4-甲磺醯基-嗎啉基甲基）-胺基]-5-三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； N -（4 -氟-3- {[2-(2 -酮-2,3-二氫-1!~1-卩引11朵_5-基胺基）- -63 - 200539871 (61) 5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； 5 - {4-[(5 -酮-嗎啉-2-基甲基）-胺基]_5-三氟甲基-喃 H定- 2 -基胺基} - 1 , 3 -二氫-吲D朵-2 -酮； N-(4 -甲氧基-3-{[2-(2_ 酮-2,3-二氫-1H-吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺； N-(4_ 甲基- 3_{[2-(2 -酮-2,3 -二氫 _1H - D引 B朵-5 -基胺 ^ 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_甲磺醯胺 > 5-[4-(3 -甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧 Π定-2 -基胺基]_1,3 -二氫-D引II朵-2 -酮； 5 - {4_[(4 -三氣乙醯基-嗎啉_2_基甲基）_胺基]-5-三氟 甲基-嘧陡-2-基胺基}-1,3_二氫-D引D杂-2 -酮； 5-{4-[(1-甲磺醯基-氮雜環丁烷-3-基甲基）-胺基]-5-三氟甲基-嘧Π定-2-基胺基卜1,3 -二氫-卩引卩朵-2-酮； » N - 甲基-N_(4 - 甲基-3-{[2-（2-嗣-2,3 - 一 氯-1H-卩引 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺； 5 - {4-[(1-甲磺醯基-吡咯烷-3-基甲基）-胺基]-5-三氟 甲基-喃Π定-2-基胺基卜1,3 -二氫-D引D朵-2-酮； 1^1-甲基-1^-{3-[2-（2-酮-2,3-二氫-1['!-卩引11朵-5-基胺基 )-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5 - {4_[2_(1_甲擴醯基-呢H定-2-基甲基）-乙胺基]-5-三 氟甲基-嘧II定-2-基胺基}-1,3-二氫-D引D朵-2-酮； -64- 200539871 (62) 5 - {4-[(4 -甲磺醯基-卩比陡-2-基甲基）-胺基]-5 -三氟甲 基-嚼D定-2-基胺基}-1,3 -二氫引D朵-2 -酮； {2,2-二甲基-3_[2-(2-酮-2,3-二氫-1日-吲哚-5-基胺 基）-5 -三戴甲基-喃Π定-4-基胺基]-丙基卜胺基甲酸第三丁 酯； 5 - [4-(3-異丙氧基-丙胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1，3 -二氣-D引D朵-2 -酮； 5 - {4-[(1-甲基-呢陡-3_基甲基）-胺基]-5-三氟甲基-嘧Π定-2 -基胺基卜1,3 -二氫-D引D朵-2_酮； 5 - {4-[(四氫卩比喃-4-基甲基）-胺基]-5-三氦甲基-嘧 D定- 2 -基胺基} - 1 , 3 -二氫-D引Π朵-2 -酮； 5-[4-(2 -乙基-丁胺基）-5 -三氧甲基-嘧陡-2-基胺基]-1,3 -二氫-D引D朵-2-酮； 5 - {4-[(四氫呋喃-2 R-基甲基）-胺基]-5-三氟甲基-嘧 π定- 2 -基胺基} - 1 , 3 -二氫-D引D朵-2 -酮； 5-{4-[(四氫呋喃- 2S-基甲基）_胺基]-5-三氟甲基-嘧 Β定-2-基胺基卜1,3 -二氫-D引D朵-2-酮； 5 - {4-[(5_甲基-卩夫喃-2-基甲基）-胺基]-5 -三氟甲基-嘧Π定-2 -基胺基} - 1 , 3 -二氫-吲D朵-2 -酮； 5-{4-[(1_甲磺醯基-吡咯烷-2-基甲基）-胺基]_5_三氟 甲基-嘧Π定-2 -基胺基卜1，3 -二氫-D引D朵-2 -酮； 5 - {4-[(金剛烷-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲D朵-2-酮； 5-{4-[(金剛烷-2-基甲基）_胺基]-5-三氟甲基-嘧啶- -65- 200539871 (63) 2-基胺基}_1，3 -二氫-D引D朵-2-酮； 5-[4-(2-甲氧基-2-甲基-丙胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二氫-D引D朵-2-酮； 5 - {4-[(內-雙環[2.2.1]庚-5-嫌-2-基甲基）-胺基]- 5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； (3-{[2-（2-酮-2,3 -二氫-1H-吲哚-5-基胺基）- 5-三氟 甲基-嘧啶-4-基胺基]-甲基卜苯甲基）-膦酸二甲酯； 5 - [4-(3-甲基-丁胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3 -二氫-D引H朵-2 -酮； 5 - {4-[(2-羥基-環己基甲基）-胺基]-5-三氟甲基-嘧 Π定-2-基胺基}-1,3 -二氫-D引D朵-2-酮； N -（4-甲氧基-3-{[2-(2_ 嗣-2,3-二氮-1H - D引 D朵-5- 基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-.甲基-甲磺醯胺； 5 - {4-[(4 -乙磺醯基-嗎啉-2-基甲基）-胺基]-5 -三氟甲 基-嘧陡-2-基胺基）-1,3 -二氫-D引D朵-2 -嗣； 5 -（4-{[4-(丙-2-磺醯基）-嗎啉-2-基甲基]-胺基}-5-三 氟甲基-喃陡-2-基胺基）-1,3 -二氫-D引D朵-2-嗣； 5 - {4-[(4_乙酿基-嗎啉-2 -基甲基）-胺基]-5-三氟甲 基-嘧B定-2 -基胺基卜1,3 -二氫-D引B朵-2 -酮； 5-{4-[(4_丙醯基-嗎啉-2 -基甲基）-胺基]-5 -三氟甲 基-嘧Π定-2 -基胺基} - 1，3 -二氫-吲D朵-2 -酮； 5-(4-{[4-(2,2-二甲基-丙醯基）-嗎啉基甲基]-胺 基卜5-三氟甲基-嘧啶-2-基胺基）-1，3-二氫-吲哚-2-酮； -66- 200539871 (64) 2-{[2-(2-酮-2,3-二氫-1H-卩引D朵-5-基胺基）-5-三氟甲 基-赌D定-4-基胺基]-甲基卜嗎啉-4_甲酸甲醋； 5 - {4-[(4_甲氧基乙醯基-嗎啉-2-基甲基）-胺基]-5-三 氟甲基-嘧D定-2-基胺基}-1,3_二氫-D引D朵-2-酮； 5 - [4_ (3-乙磺醯基-苯甲胺基）-5-三氟甲基-嘧啶-2-基胺基]_1，3 -二氫-D引D朵-2-酮； 5-{4-[(4_甲磺醯基-嗎啉- 2R-基甲基）-胺基]-5 -三氟 H 甲基'•喃Π定-2 -基胺基}-1,3 -二氫-D引D朵-2-酮； 5 一 {4_[(4_甲磺醯基-嗎啉- 2S-基甲基）-胺基]-5-三氟 甲基-嘧Π定-2-基胺基}-1,3-二氫-D引D朵-2 -酮； 5-{4-[(嘧啶-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基}-1，3_二氫-D引D朵-2-酮； 5 - {4-[(D比D秦-2-基甲基）-胺基]-5 -三氟》甲基-嘧D定-2-基胺基} - 1，3 -二氫-D引D朵-2 - _ ; N -（4 -氟-3- {[2-(2 -酮- 2,3 -二氫-1H-D引 D朵-5-基胺基）-® 5-三氟甲基-嘧啶-4-基胺基]-甲基}-苯基）-N -甲基-甲磺 醯胺； 5 - {4-[(1-甲擴醯基-呢陡-3-基甲基）-胺基]-5-三氟甲 基-嘧H定-2-基胺基}-1,3 -二氫-吲哚-2-酮； 5 - {4-[(4-異丁醯基-嗎啉-2-基甲基）-胺基]-5-三氟甲 基-嘧陡-2-基胺基卜1,3 -二氫-吲D朵-2 -酮； 5 - [4-(3,3-二甲基-2-酮-丁胺基）-5-三氟甲基-嘧啶-2-基胺基]-l，3-二氫-D引D朵-2-酮； 5 - [4-(1,2-二甲基-丙胺基）-5 -三氣甲基-嘧卩定-2 -基胺 -67- 200539871 (65) 基]-1，3-二氫-吲B朵-2-酮； 5-[4-(2-甲氧基-卜甲基-乙胺基）-5_三氟甲基-嘧啶-2-基胺基]-1,3-二氫-D引D朵-2-酮； 5 - U-[2-(1,1-二酮-1D6-異噻唑烷-2-基）-乙胺基]- 5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - [4-(3-甲胺基-丙胺基）-5 -三氟甲基-喃淀-2 -基胺 基]-1,3 -二氫-D引D朵-2-酮； B 5 - {4-[(D比陡_3_基甲基）-胺基]-5 -三氟甲基-嘧陡-2- 基胺基卜1，3 -二氫-D引D朵-2 -酮； 5- {4-[(6-甲磺醯基-吡啶-2-基甲基）-胺基]-5-三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[3-(1，1_二酮-1,1,6 -異噻_院-2-基）-苯甲胺基 ]-5 -三氟甲基-喃卩定_2_基胺基}-1,3-二氫-卩引D朵-2 -嗣； 5 - [4-(lR-苯基-乙胺基）-5 -三氟甲基-嘧、陡-2-基胺基 ]- 1，3 -二氫-吲哚-2 -酮； B 5 -（4 -異丙胺基-5 -三氟甲基-嘧η定-2 -基胺基）-1，3 -二 氫-吲哚-2-酮； 5 -（4 R-第二丁胺基-5-三氟甲基-嘧啶-2-基胺基）-1,3-二氫-吲哚-2-酮； 5 -（4 S-第二丁胺基-5-三氟甲基-嘧啶-2-基胺基）_ 1，3-二氫-卩引11朵-2-酮； 5-[4_(2_甲胺基-乙胺基）-5-三氟甲基-嘧啶-2-基胺 基]-1,3 -二氫-D引D朵-2 -酮； 5 - [4_(1S -苯基-乙胺基）-5 -三氟甲基-II·密D定-2 -基胺基 -68- 200539871 (66) ]-1，3_二氫-吲哚-2-酮； 5 - {4-[(2-甲磺醯基甲基-噻唑-4-基甲基）-胺基]-5-三 氧甲基-喃Π定-2-基胺基}-1，3 -二氫-D引D朵-2-酮； 5 -（4-丙胺基-5-三氟甲基-赌D定-2-基胺基）-1，3-二 氫-卩引D朵-2-酮； 5-[4-(2-經基-1-甲基-乙胺基）-5-三氟甲基-嘧卩定- 2-基胺基]-1,3-二氫-D引D朵-2-酮； B 5-[4-(1-經甲基-丙胺基）-5-三氟（甲基-喃D定-2 -基胺 基]-1,3-二氫-吲哚-2-酮； 5-{4-[(5-甲磺醯基-吡啶-3-基甲基）-胺基]-5-三氟甲 基-喷Π定-2-基胺基}-1,3-二氫-D5|D朵-2-酮； 5 - {4-[(卩比陡-4 -基甲基）-胺基]-5 -三氣甲基-嘧陡-2-基胺基卜1,3 -二氫-D引D朵-2 -酮； 5-[4-(1,3 -二甲基-丁胺基）-5-三氟甲基-喃Π定-2-基胺 基]-1，3 -二氫-D引U朵-2-酮；Ce), and it is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, a CN,-(Ci-c6) alkyl, a nr5r6, _〇R12, a (C "C7) naphthene Group,-(c2-c9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8; R2 is hydrogen; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R1 Is selected from the group consisting of a 3-CJ cycloalkyl group and a-(c2-c9) heterocyclic group, and it is optionally passed through 1 to 3 atoms of hydrogen, halogen, meridian, -CN,-(C ^ -Ce) Yuan base, -NR5R6, -OR12 ... (C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, -c02R12, '57 · 200539871 (55) -CONW, and -COMR5R «group Is substituted; R2 is hydrogen; and 0 is 2 The present invention also includes a compound other than Formula 1, which is selected from -0 (CrC6) alkyl, -0 (C3-C7) cycloalkyl, and-. (C2_c9) heterocyclyl 'and it is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -CN,-(c-C6) alkyl, -NR5R6, -OR12, a (q-C7) ring Alkyl,-(c2-C9) heterocyclyl, -CO2R] 2, -CONR5R6, and -coNR5R8 are substituted by the group B; R2 is hydrogen; and n is 2. One system of the invention is a compound represented by Formula 1, wherein R1 is -NR5R6, and it is optionally selected from hydrogen, halogen, hydroxyl, -CN,-(CrC6) alkyl, -NR5R6, -〇R ", mono (C" C7) cycloalkyl,-(c2-c9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8; R2 is hydrogen; and η is 2 Another system of the present invention is a compound represented by Formula 1, wherein R1 I is selected from -SR7, -SOR7, -S02R7, and -S02NR5R6, and it is optionally selected from hydrogen and halogen by 1 to 3 , Hydroxyl, -CN,-(Ci-Cj alkyl, -MW, -OR ",-(ere?) Cycloalkyl,-(C2_c9) heterocyclyl, -C02R12, -CONR5R6, and -CONR5R8 R2 is hydrogen; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R1 is -C02R ", -CONW, -NHCOR] 2, -NR] 2CONR5r6, or -NR12S02R7 , And it is optionally selected from 1 to 3 hydrogen, halogen, hydroxyl, -CN,-(C) -C6) alkyl, -NR5R6, -OR12,-(C3-C7) cycloalkyl,-( C2 * »C9) heterocyclyl, -C〇2R12, -CONR5R6, and -CONR5R8 -58- 200539871 (56 ); R2 is hydrogen; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R2 is hydrogen or-(C ^ CJ alkyl, and it is optionally selected from hydrogen, halogen, halogen, -N02, -CN, -(C ^ -Ce) courtyard,-(C2_C6) alkyl,-(C2-C6) alkynyl, -C = N-〇H, -C = N-〇 ((C "C6) alkyl), -NR5R6, -OR,-(C3-C! 7) ring courtyard,-(C2-C9) heterocyclyl, -C02R12, -CONR5R6, -CONR5R8, -Sr7, -s〇r7, -s. 2R7, -S02NR5R6, -NHCOR12, -NR12CONR5R6, and -NR12S02R7 are substituted, wherein-(C2-C6) alkenyl and -Ce) alkynyl of the R2 group can be optionally passed through 1 to 3 RU groups Is substituted by a group; is hydrogen; and η is 2. The present invention also provides a compound represented by Formula 1, wherein R2 is a _ (C3-CT) ring group or a-(CfC: 9) heterocyclic group, and any 1 to 3 of the earth warp are respectively selected from hydrogen, halogen, hydroxyl, -N02, -CN,-(C ^ CJ alkyl,-(C2-C6) anhydrol,-(C2-C6) alkynyl, -c = N-〇H, -C = N-0 (((^-(^ 6) fluorenyl), -nr5r6, -or ",-(C3_C7) cycloalkyl, _ (C2-Cs) heterocyclyl,- C02R12, -CONR5R6, -coNR5R8, -SR7, -s〇r7,-S02R7, -S02NR5R6, ~ NHC0R12, -NR12CONR5R6, and-NR12S〇2R7 are substituted, wherein the _ (C2-C6) alkenyl and-(q-C6) alkynyl of the ... group may be optionally passed through 1 to 3 R 1 is hydrogen; and η is 2. Another system of the present invention is a compound represented by Formula 1, wherein R 2 is -CO 2 R 12 and -CONR 5 R 6, and it is optionally 3 are selected from hydrogen, halogen, hydroxyl, -N〇2, -CN,-(Ci_C6) alkyl,-(C2_C6) alkenyl, _ (C2-C6) alkynyl-c = N-〇H, _Ο .0 ((Κ6) alkyl), -59- 200539871 (57)-NR5R6, -〇R12,-(C "C7) cycloalkyl,-(c2-c9) heterocyclyl, -C〇2R12,- CONR5R6 '-a CQNR5R8, -Sr7, _s〇R7, _5〇 ^ 7, _s〇2nr5r6, a nhcor12, a NR12C〇NR5r6, and a nr12S〇2R7 group, where the R2 group- (C2-c6) alkenyl and-(c2-c6) alkynyl may be optionally substituted with 1 to 3 R12 groups; R1 is hydrogen; and η is 2 The present invention also provides a compound represented by Formula 1. , Where R1 and R2 and the atom to which B is connected together form a _ (C3_C1 ()) ring radical, and it is optionally selected from hydrogen and halogen by 1 to 3, respectively Hydroxyl, -N02, -CN,-(C "C6 :) Yuan base, (C2 ~ * C6) alkyl group,-(C2-C6) fast group, ~ c = N- 0H, -C = N * ~ 0 ((C "C6) Yuanji), -NR5R6, -OR12,-(C3-C7) ring Yuanji, _ (C2 ~~ C9) heterocyclic group, one C 〇2 R 12, one C 〇NR 5 R6 , — ◦〇n R5 R8, -s R7, -SOR7, -s02R7, -s02NR5R6, -nhcoru, -NR12CONR5R6, and -NRl2S〇2R7, wherein- The (CrC6) alkenyl and-(CrC6) alkynyl may be optionally substituted with 1 to 3 > groups. The present invention also provides a compound represented by Formula 1, in which ... and-together with the connected atom form a-(q-C9) heterocyclic group, which is optionally selected from hydrogen, halogen, and hydroxyl through i to 3 , -N〇2, —CN, — Yuanji,-(C 2-c 6) anhydroxyl,-(c 2 -C 6) alkynyl, -c =: N-ο Η, _ C = N _ 〇 ((c〗 -c6) alkyl), --nr5r6, --ori2,-(C3_C7) ring courtyard group,-(c2-c9) heterocyclic group, --c02Rl2, --c〇NR5R6, ~ c0nr5r8, _sr7, -S7R7, -S02R7, __s〇2Nr5r6, -NHC〇r12, -NR " CONR5R6, and -NR " s〇2R7 are substituted, wherein the cyclic-60-200539871 (58) The-(C2-C6) alkenyl and-(C2-C6) alkynyl groups of the group may be optionally substituted with 1 to 3 R12 groups. The present invention also provides a compound represented by Formula 1, wherein R1 and R2 together with the connected atoms form-(C3-C1 ()) cycloalkyl, which is optionally selected from hydrogen and halogen via 1 to 3, respectively. , Hydroxyl, -n〇2, -CN,-(C 丨 -C6) fluorenyl,-(C2-C6) alkenyl,-(C2-C6) alkynyl, -C = N-OH, -C = N-〇 ((C 1-C 6) Academic Group), -N R5 R6,-〇R 12,,-(C 3-C 7) Ring Academic Group, ® _ (C2-C9) heterocyclic group, -C02R12, _C〇NR5r6, -C〇NR5R8, _SR7, -SOR7, -so2R7, _S02NR5R6, -NHC0Ri2,-NR12C〇NR5R6, and -NR12S02R7 are replaced by the-(C2-C6) ene And-(c2_c6) alkynyl may be optionally substituted with 1 to 3 R12 groups; and n is 1. The present invention also provides a compound represented by Formula 1, wherein R1 and R2 form a-(G2-C $) heterocyclyl together with the atoms to which they are attached, and they are optionally selected from hydrogen, halogen, Hydroxyl, -N02, -CN,-(C ^ -Ce) courtyard,-(C2-C6) anhydroxyl, _ (C2_C6) alkynyl, -C = N-OH, -C = N_〇 ((Κ6) Alkyl), -NR5R6, -OR12,-(C3-C7) ring courtyard,-(c2-c9) heterocyclyl, _co2r12, _connr5r6, one conr5r8, one sr7, -SOR7, -S02R7,-S02NR5R6 ,-NHCOR12, one NR12C〇NR5R6, and one NR12so2R7 are substituted, in which the ~ * (C2_C6) group of the cyclic group and the-(C2 " ~ C6) fast group can be optionally passed through 1 to 3 R12 is substituted; and n is 1. In a preferred system, R4 is a substituent selected from the group consisting of hydrogen,-(C! -C6), _ (c "C7) cycloalkyl, and-(CfC9) heterocyclyl; wherein the y substituent is- 61-200539871 (59)-(CrC6) alkyl,-(c3 1 to 3 hetero atoms selected from hydrogen -CN, -NR5R6, -OR12, -C02R12, and -CONR5 R4 substituents Not -c7) cycloalkyl and-(c2-c9) heterocyclyl are arbitrary, halogen, meridian,-(C1-C6) cyclo,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl Substituted by the group of R8: its prerequisite is that it can be bonded to the SP 3 carbon atom bonded to another heteroatom; and wherein R5 and R8 in -CONR5R8 can be formed together with the linked atom -(C3-CI ()) cyclofluorenyl or-(C2-c9) heterocyclyl. In another preferred system, R4 is hydrogen. In addition, the present invention provides a compound represented by formula 1, wherein R5 and R6 is each a substituent selected from hydrogen and an alkyl group, respectively, and it is optionally substituted with the above-mentioned group. A special system of the present invention is a compound selected from the group consisting of 1 ^-(1-methyl-1-phenyl -Ethyl) -3-{[2- (2-keto-23 —dihydro-1 cardiolidene-5-ylamino) -5-trifluoromethyl-pyrimidinylamine ] -Methyllbenzamide; 3-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methylbenzylsulfosylamine; 5- {4- [3- (trifluoromethanesulfonyl) -benzylamino] trifluoromethyl-pyrimidine-2 -ylaminobenzyl 1 , 3 -dihydro-indole-2-one; 5- {4_ [(piperidin-3-ylmethylpyrimidinyl] -5 -trifluoromethyl-pyrimidin-2-ylaminobenzyl 1,3 -Dihydro-indole-2-one; 5-{4-[(trimethylsulfonyl-piperidine_3-ylmethyl) -amino group 5-trifluoromethyl-pyrimidin-2-ylamine N- (3-U2- (2_one-2,3-dihydro-1H-indole-5-ylamino) _5-tri-62- 200539871 (60) Fluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; 3-keto-3 (3-{[2- (2-keto-2,3_dihydro-1H) -Hydrazol-5-ylamino) _ 5-trifluoromethyl-pyrimidin-4-ylamino] -methylpiperidin-1-yl) -propionitrile; 5- {4- [3 -(1,1-Difluorene-1N6-isothiazoline-2-yl) -propylamino] -5-trifluoromethyl-pyrimidino-2-ylamino group 1,3-dihydro-fluorene Pandolin-2-one; 5-[4- (2-methyl-butylamino) -5-trifluoromethyl-pentidin-2-ylamino] -1,3-dihydro-D D-2-2 5-{4-[(1_Methanesulfonyl- 丨 radiodin-2-ylmethyl) -amino] -5-trifluoromethyl-annino-2-ylamino} -1, 3_dihydro-codo 丨 D-do-2 -one; N-{2- [2- (2-keto-2,3 -dihydro-1H-B D-do-5_ylamino) -5_ three Fluoromethyl-pyrimidin-4-ylamino] -ethyl} -methanesulfonamide; N- {4_ [2- (2-keto-2,3-dihydro-1H-indole-5-ylamine Yl) -5-trifluoromethyl-pyrimidin-4-ylamino] -butylmethanesulfonyl amine; 5-{4-[(1_methylsulfonyl-benzyl-4-ylmethyl) -Amine] -5_trifluoromethyl-anhydro-2-damino-2-ylamino 1,3-dihydro-D-indol-2-one; N-methyl-N- {2-[2 -(2-keto-2,3-dihydro-1H-D-D-5-ylamino) _5_trifluoromethyl-penta-4-amino ; 3-{[2- (2-keto-2,3-dihydro-1H-D methyl-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl esters; N-{3- [2- (2_one-2,3 -dihydro-1H-D-D-5-ylamino) _5-trifluoromethyl-pyrimidine- 4-ylamino] -propylsulfanilamide; 5- {4-[(4-methylsulfanyl-morpholinylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -Aminoaminob 1,3-dihydro-indole-2-one; N-(4-fluoro-3- {[2- (2-one-2,3 -Dihydro-1! ~ 1-1-Hydroxy 11-5-amino group)--63-200539871 (61) 5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenyl -Methanesulfonamide; 5-{4-[(5-keto-morpholin-2-ylmethyl) -amino] -5 -trifluoromethyl-ranoxidine-2 -ylamino}-1, 3 -dihydro-indodo-2 -one; N- (4-methoxy-3-{[2- (2_one-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; N- (4-methyl-3 _ {[2- (2-keto-2,3- Dihydro_1H-D-B-5 (5-ylamine ^ yl) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) _methanesulfonamide > 5- [ 4- (3-Methanesulfonylmethyl-benzylamido) -5-trifluoromethyl-pyrimidine-2 -ylamino] _1,3-dihydro-D ; 5-{4 _ [(4-trifluoroacetamido-morpholine-2-ylmethyl) _amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3_ Dihydro-D-D hetero-2 -one; 5- {4-[(1-methylsulfonyl-azetidin-3-ylmethyl) -amino] -5-trifluoromethyl- Pyrimidine-2-ylaminob, 1,3-dihydro-pyridine-2-one; »N-methyl-N_ (4-methyl-3-{[2- (2-fluorene- 2,3-Chloro-1H-pyridine D-5-ylamino) -5-tri Fluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine; 5-{4-[(1-methylsulfonyl-pyrrolidin-3-ylmethyl) -amine [] Yl] -5-trifluoromethyl-annino-2-ylaminopyridine 1,3-dihydro-Dendor-2-one; 1 ^ 1-methyl-1 ^-{3- [ 2- (2-keto-2,3-dihydro-1 ['!-Fluorenyl 11-5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -propylbenzene Methanesulfonylamine; 5-{4_ [2_ (1_Methylsulfenyl-n-Hd-2-ylmethyl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamine } -1,3-dihydro-D-D-Dan-2-one; -64- 200539871 (62) 5-{4-[(4 -Methanesulfonyl-pyridine-2-ylmethyl) -Amine] -5 -trifluoromethyl-d-Did-2-ylamino} -1,3-dihydronaphthyl-2 -one; {2,2-dimethyl-3_ [2- (2-keto-2,3-dihydro-1day-indol-5-ylamino) -5-tris-methyl-anidin-4-ylamino] -propyltriphenylaminocarboxylic acid tert-butyl Esters; 5-[4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-digas-D ; 5-{4-[(1-methyl-nesto-3_ylmethyl) -amino group] -5-trifluoromethyl-pyrimidine-2 -ylamino group 1,3-dihydro -D D-2-2 ketone; 5-{4-[(tetrahydropyran-4-ylmethyl)- Yl] -5-trihelylmethyl-pyrimidin-2-diylamino}-1, 3 -dihydro-D iodo-2-one; 5- [4- (2-ethyl-butylamine ) -5 -trioxomethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-one; 5-{4-[(tetrahydrofuran-2 R-ylmethyl ) -Amino] -5-trifluoromethyl-pyridine-2-ylamino}-1, 3 -dihydro-D-D-2-2-one; 5- {4-[(tetrahydrofuran- 2S-ylmethyl) _amino] -5-trifluoromethyl-pyrimidine-2-ylamino group 1,3 -dihydro-D-D-2-one; 5-{4- [ (5-methyl-oxan-2-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidine-2 -ylamino}-1, 3 -dihydro-indole- 2-ketone; 5- {4-[(1-methylsulfonyl-pyrrolidin-2-ylmethyl) -amino] -5_trifluoromethyl-pyrimidine-2 -ylamino group 1, 3-dihydro-D-D-2-2-one; 5-{4-[(adamantane-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indodol-2-one; 5- {4-[(adamantane-2-ylmethyl) _amino] -5-trifluoromethyl-pyrimidine- -65- 200539871 ( 63) 2-Aminoamino} _1,3-dihydro-D-D-2-one; 5- [4- (2-methoxy-2-methyl-propylamino) -5-trifluoromethyl -Pyrimidin-2-ylamino] -1,3-dihydro-D 5-{4-[(Inner-bicyclo [2.2.1] hept-5-an-2-ylmethyl) -amino]-5-trifluoromethyl-pyrimidin-2-ylamino group 1,3 -Dihydro-indole-2-one; (3-{[2- (2-one-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine 4-ylamino] -methylphenylbenzyl) -phosphonic acid dimethyl ester; 5- [4- (3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-yl Amine] -1,3 -dihydro-D-H 2 -2 -one; 5-{4-[(2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidine N--2-ylamino} -1,3-dihydro-D-D-do-2-one; N-(4-methoxy-3-{[2- (2_ 嗣 -2,3-diazepine -1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl)-. Methyl-methanesulfonamide; 5-{ 4-[(4-Ethylsulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-D D -2 -fluorene; 5-(4-{[4- (prop-2-sulfonyl) -morpholin-2-ylmethyl] -amino} -5-trifluoromethyl-pyridine -2-ylamino) -1,3 -dihydro-D-D-2-yl; 5-{4-[(4-ethylethyl-morpholine-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2,2-aminoaminob 1,3-dihydro-D, B-2, 2-one; 5- {4- [ (4-propionyl-morpholine-2 -ylmethyl) -amino] -5 -trifluoromethyl-pyrimidine-2 -ylamino}-1,3 -dihydro-indole- 2-ketone; 5- (4-{[4- (2,2-dimethyl-propionyl) -morpholinylmethyl] -amino group 5-trifluoromethyl-pyrimidin-2-ylamine ) -1,3-dihydro-indole-2-one; -66- 200539871 (64) 2-{[2- (2-keto-2,3-dihydro-1H-pyridine-5) -Methylamino) -5-trifluoromethyl-d-Did-4-ylamino] -methyl morpholine-4-formic acid methyl acetate; 5-{4-[(4_methoxyacetamidine -Morpholine-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-Dendor-2-one; 5-[4_ (3-Ethylsulfenyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] _1,3-dihydro-Dendor-2-one; 5 -{4-[(4-Methanesulfonyl-morpholine-2R-ylmethyl) -amino] -5 -trifluoroH methyl '• annidine-2 -ylamino} -1,3 -Dihydro-D-D-D-2-one; 5-mono {4 _ [(4_methylsulfonyl-morpholine-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine -2-ylamino} -1,3-dihydro-D-D-2-2-one; 5- {4-[(pyrimidin-2-ylmethyl) -amino] -5-trifluoromethyl -Pyrimidin-2-ylamino} -1,3_dihydro-D-D-2-one; 5-{4-[(D 比 D 秦-2-ylmethyl) -amino] -5 -trifluoro "methyl-pyrimidin-2-ylamino}-1,3-dihydro-D-D-2-_; N-( 4-Fluoro-3- {[2- (2-keto-2,3-dihydro-1H-D-D-5-ylamino) -® 5-trifluoromethyl-pyrimidin-4-ylamine Group] -methyl} -phenyl) -N-methyl-methanesulfonylamine; 5-{4-[(1-methylsulfenyl-mento-3-ylmethyl) -amino] -5 -Trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one; 5-{4-[(4-isobutylfluorenyl-morpholin-2-ylmethyl) ) -Amino] -5-trifluoromethyl-pyrimidino-2-ylamino group 1,3-dihydro-indodo-2-2-one; 5-[4- (3,3-dimethyl 2--2-keto-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-one; 5-[4- (1 , 2-Dimethyl-propylamino) -5 -trifluoromethyl-pyrimidine-2 -ylamine-67- 200539871 (65) yl] -1,3-dihydro-indodol-2-one ; 5- [4- (2-methoxy-bumethyl-ethylamino) -5_trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D Ketone; 5-U- [2- (1,1-dione-1D6-isothiazolidin-2-yl) -ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino group 1, 3-dihydro-indole-2-one; 5-[4- (3-methylamino-propylamino) -5 -trifluoromethyl- Yodo-2 -ylamino] -1,3-dihydro-D-D-2-one; B 5-{4-[(D ratio steep_3-methylmethyl) -amino] -5- Trifluoromethyl-pyrimidin-2-ylaminob, 1,3-dihydro-D-D-2-2-one; 5- {4-[(6-methylsulfonyl-pyridin-2-ylmethyl) ) -Amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one; 5-{4- [3- (1,1-di Keto-1,1,6-isothiothiazin-2-yl) -benzylamino] -5 -trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-fluorene D -2-hydrazone; 5-[4- (lR-phenyl-ethylamino) -5 -trifluoromethyl-pyrimidine, acryl-2-ylamino]-1,3-dihydro-ind Indole-2 -one; B 5-(4-isopropylamino-5 -trifluoromethyl-pyrimidine-2 -ylamino) -1,3-dihydro-indole-2-one; 5- (4 R-Second-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole-2-one; 5-(4 S-Second-butylamine Methyl-5-trifluoromethyl-pyrimidin-2-ylamino) _ 1,3-dihydro-pyridine 11-2-one; 5- [4_ (2-methylamino-ethylamino)- 5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-2-one; 5-[4_ (1S -phenyl-ethylamino) -5 -tri Fluoromethyl-II · dididine-2 -ylamino-68- 200539871 (66)] -1 3-dihydro-indole-2-one; 5-{4-[(2-methylsulfonylmethyl-thiazol-4-ylmethyl) -amino] -5-trioxomethyl-ran Amine-2-ylamino} -1,3-dihydro-D-D-2-anone; 5-(4-Propanyl-5-trifluoromethyl-D-Amino-2-ylamino) -1,3-dihydro-pyridine-2-dol; 5- [4- (2-Cyclo-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidine-2 -Amino group] -1,3-dihydro-D-D--2-one; B 5- [4- (1- Via methyl-propylamino) -5-trifluoro (methyl-pyridine) -2 -ylamino] -1,3-dihydro-indole-2-one; 5- {4-[(5-methylsulfonyl-pyridin-3-ylmethyl) -amino] -5 -Trifluoromethyl-pentin-2-ylamino} -1,3-dihydro-D5 | Ddor-2-one; 5-{4-[(卩 比 卩 -4 -ylmethyl) -Amine] -5 -trifluoromethyl-pyrimidino-2-ylaminob, 1,3-dihydro-D-D-2-2-one; 5- [4- (1,3-dimethyl -Butylamino) -5-trifluoromethyl-amino-idin-2-ylamino] -1,3-dihydro-Dindol-2-one;

I 1^-異丙基-1^-{3-[2-（2-酮-2,3_ 一 氫-1H-D引 D朵-5 -基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5-[4-(lS-羥甲基-2 -甲基-丙胺基）-5-三氟甲基-嘧 啶-2-基胺基]-1,3-二氫-吲哚-2-酮； N -環己基- N_{3-[2-(2 -酮- 2,3 -二氫-1H-D引卩朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5 - [4-(1,2,3,4-四氫萘-卜基胺基）-5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-D引D朵-2-酮； 5-{4-[(1_甲磺醯基-吡咯烷- 2S-基甲基）-胺基]_5-三 -69 - 200539871 (67) 氟甲基-喃D定-2-基胺基}-1,3 -二氫-D引D朵-2-酮； 5-{4-[(3-甲基-噻吩_2_基甲基）-胺基]-5-三氟甲基-赔D定-2 -基胺基卜1 , 3 -二氫-D引D朵-2 -酮； 5-{4-[(1-甲磺醯基-吡咯烷-3R-基甲基）-胺基]_5-三 赢甲基-嚼Π定-2 -基胺基}-1,3_二氫-D引D朵-2-酮； 5-[4-(2_經基-1S-苯基-乙胺基）-5_三氟甲基-嘧B定-2-基胺基]-1,3 -二氫-Π引D朵-2-酮； I 5-[4-(2 -經基-1S -甲基-乙胺基）-5-三氣甲基-喃B定- 2-基胺基]-1,3-二氫-吲哚-2-酮； 5-[4-(1R-羥甲基-丙胺基）-5-三氟甲基-嘧啶-2-基胺 基]-1,3-二氫-吲哚-2-酮； 5 - [4-(1-嘧、Π定-4-基-乙胺基）-5-三氟甲基-嘧Π定-2-基 胺基]二氫-D引D朵-2_酮； 5 - [4_(1，1-二酮-四氫-1-噻吩-3 -基胺基）-5 -三氟甲 基-嘧、Π定-2 -基胺基]-1，3 _二氫-D引D朵-2 -酮； B 5-{4-[(1H-咪唑-2-基甲基）_胺基]-5-三氟甲基-嘧啶- 2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - [4-(2-嘛陡-2-基-乙胺基）_5_三氟甲基-喃陡-2-基 胺基]_1，3 -二氫-D引D朵-2-酮； 5 - [4-(異丁基-甲基-胺基）-5 -三氟甲基-嘧陡_2 -基胺 基]-1,3-二氫-吲哚-2-酮； N- 甲基-N -（3-{[2-(2- 酮 _2,3-二氫-1H - D 引 D朵 _5_ 基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 -70- 200539871 (68) 1^-乙基-1^_(3-{[2-(2-酮-2,3-二氫-1}^-卩引卩朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 $ 5 - [4-(2-甲磺醯基-苯甲胺基）-5-三氟甲基-嘧啶-2-基胺基]_ 1，3 -二氫-D引D朵-2 -酮； N-異丙基-N-（3-{[2-（2-嗣-2,3-二氫_lH-D引D朵-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺； 5-{4_[(3,4,5,6 -四氫-2H-[1，2’]聯卩比 Π定-3-基甲基）-胺 基]-5 -三氣甲基-嘧Π定-2-基胺基}_1,3_二氫-卩引卩朵-2- _ ; 5-{4-[(1_喃陡-2-基-呢B定-3-基甲基）-胺基]三氣 甲基-嘧Π定-2-基胺基}-1,3_二氫-D引D朵-2 -酮； 5 - {4-[2R-(1-甲磺醯基-派0定-2-基）-乙胺基]-5 -三氣 甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5-{4-[2S-(1_甲磺醯基-呢陡-2 -基）-乙胺基]-5 -三氟 甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - [4-(3-甲硫基-丙胺基）-5 -三氟甲基-喃Π定-2 -基胺 基]-1,3 -二氫-D引D朵-2-酮； 5-[4-(lS-羥甲基-3-甲硫基-丙胺基）-5-三氟甲基-嘧 B定-2-基胺基]-1,3-二氫-D引0朵-2-酮； 5 - [4-(2 -經基-1R -甲基-乙胺基）-5 -三氟甲基-嚼陡-2-基胺基]-1,3 -二氫-D引D朵-2-酮； 5 - [4-(lR-羥甲基-2 -甲基-丙胺基）-5-三氟甲基-嘧 Π定-2 -基胺基]-1，3 -二氫-吲D朵-2 -酮； -71 - 200539871 (69) N-乙基-N-{3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基 )- 5 -三氟甲基-喃B定-4-基胺基]-丙基卜甲擴醯胺； 5 - {4-[U-甲磺醯基-吡咯烷-3 R-基甲基）-胺基]-5-三 氟甲基-嘧啶_2_基胺基卜1,3-二氫-吲哚-2-酮； 5- [4-(lS-羥甲基-丙胺基）-5-三氟甲基-嘧啶-2-基胺 基]-1,3-二氫-D引D朵-2-酮； 5-[4-(3,5-二硝基-苯甲胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1,3-二氫_吲哚-2-酮； N-(2_{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； N - 異丙基- N_{2-[2-(2 -酮- 2,3 -二氫-1H-0引 D朵-5-基胺 基）-5 -三氟甲基-喃Π定-4-基胺基]-乙基}-甲擴醯胺； 5 - [4-(2-羥基-1-苯基-乙胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮； 5 - [4-(1R-羥甲基-3-甲基-丁胺基）-5-三氟甲基-嘧 Π定-基胺基]-1,3 -二氫-D引D朵-2-酮； 5 - [4-(1S-經甲基-3 -甲基-丁胺基）_5 -三氟甲基-嘧 Π定- 2 -基胺基]-1，3 -二氫_ D引D朵-2 -酮； 5 - {4-[(1_甲磺醯基-哌啶- 2S-基甲基）-胺基]-5-三氟 甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(1_甲擴醯基-卩比略院- 2R-基甲基）-胺基]-5-三 鎮甲基-喃陡-2-基胺基}-1，3-二氫-D引D朵-2-酮； 5 - [4-(甲基-卩比B定-2 -基甲基-胺基）-5 -三集甲基-喷 U定-2-基胺基]-1,3 -二氫-D引II朵-2 -酮； -72- 200539871 (70) 5 - {4-[(3 -甲擴醯基-苯甲基）-甲基-胺基]-5-三氟甲 基- &密D定-2 -基胺基卜1，3 -二氫-卩引卩朵-2 -酮； 1^-甲基-1^-（2-{[2-(2-酮-2,3-二氫-1}^-卩弓丨[1朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 9 5 - [4-(甲基-D比π定-3-基甲基-胺基）-5 -三氟甲基-嘧' Π定-2-基胺基]-1,3 -二氫-D引D朵-2 -酮； 5-{4_[(1-甲擴醯基-呢陡-3-基甲基）-甲基-胺基]- 5-三氟甲基-嘧卩定_2 -基胺基}-1,3 -二氫-卩引卩朵-2-酮； 5 - [4-(甲基-卩比Π定-4-基甲基-胺基）-5 -三氟甲基-嘧 陡-2-基胺基]-1,3 -二氫-D引D朵-2-酮； 5-（4 -環戊基胺基-5 -三氣甲基-喃B定-2-基胺基）-1,3 -二氫-吲哚-2-酮； 5-[4_(2,6 -二甲氧基-苯甲胺基）-5 -三氣甲基-喃Π定-2-基胺基]-1,3-二氫-吲哚-2-酮；I 1 ^ -isopropyl-1 ^-{3- [2- (2-keto-2,3_ monohydro-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidine -4-Aminoamino] -propyl sulfasalazine; 5- [4- (lS-hydroxymethyl-2 -methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamine Group] -1,3-dihydro-indole-2-one; N-cyclohexyl-N_ {3- [2- (2-one-2,3-dihydro-1H-D Ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyltrimethylsulfonamide; 5-[4- (1,2,3,4-tetrahydronaphthalene-triphenylamine) ) -5-trifluoromethyl-pyrimidin-2-ylaminopyridine 1,3-dihydro-D-D-2-one; 5- {4-[(1-Methanesulfonyl-pyrrolidine -2S-ylmethyl) -amino group] _5-tri-69-200539871 (67) fluoromethyl-amino-D-di-2-ylamino} -1,3-dihydro-D Ketone; 5- {4-[(3-methyl-thiophene-2-ylmethyl) -amino] -5-trifluoromethyl-pentadidine-2 -ylamino group 1, 3 -dihydro -D, D-2, 2-ketone; 5- {4-[(1-methylsulfonyl-pyrrolidine-3R-ylmethyl) -amino group] _5-trimethylol-methyl-2 Amino group} -1,3_dihydro-D-D-2-one; 5- [4- (2_Cyclo-1S-phenyl-ethylamino) -5_trifluoromethyl-pyrimidine B-Ade-2-ylamino] -1,3 -dihydro- hydrazine-2-one; I 5- [4- (2-Aryl-1S -methyl -Ethylamino) -5-trifluoromethyl-Branyl-2-ylamino] -1,3-dihydro-indole-2-one; 5- [4- (1R-hydroxymethyl- Propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; 5-[4- (1-pyrimidine, hydradin-4-yl -Ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] dihydro-D-D-2-2-one; 5-[4_ (1,1-dione-tetrahydro- 1-thiophen-3 -ylamino) -5 -trifluoromethyl-pyrimidine, hydradin-2 -ylamino] -1,3-dihydro-D-D-2-2-one; B 5- { 4-[(1H-imidazol-2-ylmethyl) _amino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5- [4- (2-Masal-2-yl-ethylamino) _5_trifluoromethyl-ansa-2-ylamino] _1,3-dihydro-D-naphtho-2-one; 5 -[4- (isobutyl-methyl-amino) -5 -trifluoromethyl-pyrimido-2-ylamino] -1,3-dihydro-indole-2-one; N-methyl -N-(3-{[2- (2-keto_2,3-dihydro-1H-D) D_5_ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methylbuthylphenyl) -methanesulfonamide-70- 200539871 (68) 1 ^ -ethyl-1 ^ _ (3-{[2- (2-keto-2,3-dihydro-1} ^ -Amino-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenyl -Methanesulfonylamine 5- [4- (2-Methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D D-2-2 ketone; N-isopropyl-N- (3-{[2- (2-fluorene-2,3-dihydro-1H-D) D-5-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; 5- {4 _ [(3,4,5,6-tetrahydro-2H- [1,2 ' ] Hydroxypyridine-3-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidyl-2-ylamino} _1,3_dihydro-pyridine-2- _ ; 5- {4-[(1_Aran-2-yl-? B-Aid-3-ylmethyl) -amino] trifluoromethyl-pyrimidin-2-ylamino} -1,3 _Dihydro-D-D-2-2-ketone; 5-{4- [2R- (1-Methanesulfonyl-Pyridin-2-yl) -ethylamino] -5 -trifluoromethyl- Pyrimidin-2-ylaminopyridine 1,3-dihydro-indole-2-one; 5- {4- [2S- (1-Methanesulfonyl-oxo-2-yl) -ethylamino] -5 -trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5-[4- (3-methylthio-propylamino) -5 -trifluoro Methyl-anhydro-2,1-aminoamino] -1,3-dihydro-D-di-2-one; 5- [4- (lS-hydroxymethyl-3-methylthio-propylamino) ) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-indole-2-one; 5-[4- (2- 1R -methyl-ethylamino) -5 -trifluoromethyl-chryso-2-ylamino] -1,3-dihydro-D-D-2-one; 5-[4- (lR -Hydroxymethyl-2 -methyl-propylamino) -5-trifluoromethyl-pyrimidine-2 -ylamino] -1,3-dihydro-indodo-2 -one; -71- 200539871 (69) N-ethyl-N- {3- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino)-5-trifluoromethyl-ran B N-A-4-ylamino] -propylbutanamide; 5-{4- [U-methylsulfonyl-pyrrolidine-3 R-ylmethyl) -amino] -5-trifluoromethyl -Pyrimidine_2_ylaminob, 1,3-dihydro-indole-2-one; 5- [4- (lS-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidine-2 -Amino group] -1,3-dihydro-D-D-2-one; 5- [4- (3,5-dinitro-benzylamino) -5-trifluoromethyl-pyrimidine 2-ylamino] -1,3-dihydro-indole-2-one; N- (2 _ {[2- (2-one-2,3-dihydro-1H-indole-5-yl Amine) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; N-isopropyl-N_ {2- [2- (2-one- 2,3 -dihydro-1H-0-D-5-ylamino) -5 -trifluoromethyl-annino-4-ylamino] -ethyl} -methaneamine; 5- [4- (2-hydroxy-1-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; 5- [4- (1R-hydroxymethyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidine-ylamine Phenyl] -1,3-dihydro-D-D-D-2-one; 5-[4- (1S- via methyl-3 -methyl-butylamino) _5-trifluoromethyl-pyrimidine -2 -ylamino] -1,3 -dihydro-D-D 2 -one; 5-{4-[(1_methylsulfonyl-piperidine-2S-ylmethyl) -amino ] -5-trifluoromethyl-pyrimidin-2-ylaminob, 1,3-dihydro-indole-2-one; 5-{4-[(1_methylexpanyl-pyrilidine- 2R-Methyl) -amino] -5-tris-methyl-pyran-2-ylamino} -1,3-dihydro-D-D-2-one; 5-[4- ( Methyl-fluorene ratio B-Ding-2 -ylmethyl-amino) -5 -Three sets of methyl-pentadin-2-ylamino] -1,3-dihydro-D Ketones; -72- 200539871 (70) 5-{4-[(3-Methanyl-benzyl) -methyl-amino] -5-trifluoromethyl- & Middine-2- Aminoamino group 1,3-dihydro-pyridin-2-one; 1 ^ -methyl-1 ^-(2-{[2- (2-keto-2,3-dihydro-1} ^-卩 弓 丨 [1-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide 9 5-[4- ( Methyl-D is more than πA-3-ylmethyl-amino) -5 -trifluoromethyl-pyridine 'Π 定 -2- Amine group] -1,3 -dihydro-D-D-2-2-one; 5- {4 _ [(1-Methylsulfenyl-neos-3-ylmethyl) -methyl-amino group]- 5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one; 5-[4- (methyl-pyridinium) Methylmethyl-amino) -5 -trifluoromethyl-pyrimidino-2-ylamino] -1,3-dihydro-D-D-2-one; 5- (4-cyclopentylamine -5 -trifluoromethyl-pyranyl-2-ylamino) -1,3-dihydro-indole-2-one; 5- [4_ (2,6-dimethoxy-benzyl) Amine group) -5 -trifluoromethyl-amino-idin-2-ylamino] -1,3-dihydro-indole-2-one;

5 - {4-[(1，5-二甲基-1H-D比哩-3-基甲基）_胺基]-5-三 氟甲基-嘧、陡-2-基胺基}-1,3 -二氣-D引D朵-2-酮；及 5 - [4-(2-咪唑-1-基-乙胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1，3 -二氫-D引B朵-2-酮。 本發明之一些較佳體系是選自下列之化合物： 5 - {4-[(1-甲擴醯基-暖陡-3-基甲基）-胺基]-5 -三氟甲 基-喃Π定-2 -基胺基卜1,3_二氫-吲D朵-2 -酮； N-甲基-N-{2_[2-(2_ 酮- 2,3 -二氫-1H-D 引 D朵-5_基胺基 )- 5-三氟甲基-嘧啶-4-基胺基]-乙基卜甲磺醯胺； -73- 200539871 (71) N -甲基-N- {3-[2-(2-酮-2,3-二氫-1H-U引 η朵-5-基胺基 )- 5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5 - {4_[2_(1-甲磺醯基-哌啶-2-基）-乙胺基]-5-三氟甲 基-嚼陡-2-基胺基}-1,3 -二氫-D引D朵-2-酮； 5 - {4_[(雙環[2.2.1]庚-5 -嫌-2-基甲基）-胺基]-5 -三氟 甲基-喃陡-2-基胺基卜1,3-二氫-D引Β朵-2-酮； 5-[4-(3-甲基-丁胺基）-5-三氟甲基-嘧啶-2-基胺基]-1，3-二氫-吗丨0朵-2-酮； 5 - {4-[(1_甲擴醯基-哌Π定-3-基甲基）-胺基]-5-三氟甲 基-嘧陡-2 -基胺基}-1，3 -二氫-D引D朵_2_酮； ^-異丙基-1^-{3-[2-（2-酮-2,3-二氫-11~1-卩引卩朵-5-基胺 基）-5 -三戴甲基-嘧Π定-4_基胺基]-丙基}-甲磺醯胺； 1^-環己基-1^_{3-[2-（2-酮-2,3-二氫-11^-卩引晚-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5 - {4-[2-(1-甲磺酿基-呢陡-2-基）-乙胺基]-5 -三氟甲 基-喷Π定-2-基胺基卜1,3 -二氫-D引D朵-2-酮； N-異丙基- N_{2-[2-(2-酮-2,3_二氫-1H-卩引D朵-5 -基胺 基）-5 -三氟甲基-喃卩定_4_基胺基]-乙基卜甲擴醯胺； 5-{4-[(1-甲磺醯基-吡咯烷-2-基甲基）-胺基]-5-三氟 甲基嘧、陡-2-基胺基卜1,3 -二氫-吲D朵-2_酮； 5-（4_環戊基胺基-5-三氟甲基-嘧卩定-2-基胺基）_1,3-二氫-D引H朵-2 _酮； 乙磺酸甲基-{3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜醯胺； -74- 200539871 (72) 2,2,2 -三戴-N-甲基-N- {3_[2-(2_酮- 2,3-二氫-1H- 卩引 哚-5-基胺基）_5-三氟甲基-嘧啶-4-基胺基]-丙基卜乙醯胺 > N- 甲基- N_{2_[2-(2 -酮- 2,3 -二氫 _1H-D 引 B朵-5-基胺基 )- 5-三氟甲基-嘧啶-4-基胺基]-乙基卜甲磺醯胺； 5-（4-環丁基胺基-5-三氟甲基-嘧啶-2-基胺基）-1，3-二氫-D引D朵-2-酮； 5 - {4-[2 -經基_2-(1_甲擴酿基-喊Π定-2-基）-乙胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 3- 嗣- 3_(3-{[2-(2 -酮- 2,3 -二氫-1H-D 引 d朵-5-基胺基）-5-三氟甲基-嘧Π定-4-基胺基]-甲基}-呢11定-1-基）-丙腈； 5 - {4-[(1-甲擴醯基-呢Π定-4-基甲基）-胺基]_5_三氟甲 基-嘧Π定-2-基胺基}-1，3_二氫-np朵-2-酮； 5 - {4-[(4-甲磺醯基-嗎啉-2-基甲基）-胺基]-5-三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(5-酮-嗎淋-2-基甲基）-胺基]-5-三氟甲基-嘧 D定- 2 _基胺基卜1,3 _二氫-D引D朵-2 -酮； 5 - {4_[(卜甲磺醯基-吡咯烷-3-基甲基）-胺基]-5-三氟 甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - [4-(3-異丙氧基-丙胺基）-5-三氟甲基-喃D定-2-基 胺基]-1，3 -二氫-吲D朵-2 -酮； 5 - {4-[(金剛烷-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； !^-{2,2-二甲基-3-[2-（2-酮-2,3-二氫-11^-〇引1]朵-5-基 -75- 200539871 (73) 胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5-{4-[(1-羥基-環戊基甲基）-胺基]_5-三氟甲基-嘧 D定-2-基胺基卜1，3_二氫-D引D朵-2-酮； 5 - {4-[(4-羥基-四氫吡喃-4-基甲基）-胺基]_5_三氟甲 基-嚼H定-2-基胺基卜1,3 -二氫-吲B朵-2-酮； 5-{4-[(2-羥基-環己基甲基）-胺基]-5-三氟甲基-嘧 啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - [4-(3 -甲磺醯基-丙胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1,3 -二氫-D引U朵-2-嗣； 5-{4-[(1-嘧Π定-2_基-_ D定-3-基甲基）-胺基]-5 -三氟 甲基-嘧n定-2 -基胺基} - 1 , 3 -二氫-D引D朵-2 -酮； 3 - [2 -（2 -酮- 2,3 -二氫-1H-D引D朵-5 -基胺基）_5_三氟甲 基-嘧D定-4-基胺基]-丙酸乙酯； 5 - {4-[(1-乙基-5-酮-吡咯烷-3-基甲基）-胺基]-5_三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 2，1\1-二甲基-1^-{2-[2-（2-嗣-2,3-二氨-11-1-13弓丨卩朵-5_基 胺基）-5-三氟甲基-嘧淀-4-基胺基]-乙基} - 丁醯胺； 2-甲氧基-N -甲基-N-{3-[2 -（2- 醒-2,3 -二氯-1H-D引 哚-5_基胺基）-5_三氟甲基-嘧啶-4-基胺基]-丙基卜乙醢胺 » 5 - {4_[2-(1_乙酿基-喊D定-2 -基）-乙胺基]_5 -三氟甲 基-嘧Π定-2-基胺基}-1，3_二氫-D引D朵-; 5 - {4-[(1_甲磺醯基-哌啶-2-基甲基）_胺基]-5-三氟甲 基-喃Π定-2 -基胺基卜1, 3 -二氫-吲D朵-2 -酮； -76- 200539871 (74) 5-{4-[(l -甲擴醯基-呢Π定-3-基甲基）-胺基]-5 -三氟甲 基-嘧D定-2 -基胺基} - 1 , 3 -二氫-D引D朵-2 -酮； 5 - {4-[(1-喃D定-2-基-呢陡-3-基甲基）-胺基]-5 -三氟 甲基-嘧Π定-2-基胺基}_1,3 -二氫-D引Π朵-2-酮； 3-{[2-(2-酮-2,3-二氫-1?^-0引11朵-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-甲基卜苯磺醯胺； N -（3-{[2_(2_ 酮- 2,3 -二氫-1H-D 引 D朵-5-基胺基）-5 -三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； N-(4-甲氧基 _3-{[2-(2 -酮- 2,3 -二氫-1H-D引 D朵-5- 基 胺基）-5 -三氣甲基-嘧Π定-4-基胺基]-甲基}-苯基）-甲擴醯 胺； 5 - [4-(3 -甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧 啶-2-基胺基]-1,3-二氫-吲哚-2-酮； N- 甲基 _N-(4-甲基-3-{[2*~(2 -嗣 - 2,3-二氮-1H- 卩弓 | D朵-5 -基胺基）-5 -三氣甲基-嘧陡_4 -基胺基]-甲基}_苯基）-甲 磺醯胺； 5 - {4-[(4-甲磺醯基-吡啶-2-基甲基）-胺基]_5_三氟甲 基-嘧陡-2-基胺基卜1,3 -二氫-卩引晚-2-酮； 5 - {4-[(5 -甲基-呋喃-2-基甲基）-胺基]-5-三氟甲基-喃Π定-2-基胺基卜1,3 -二氫-D引B朵-2-酮； (3 - {[2-(2-酮- 2,3-二氫-1Η-吲哚-5-基胺基）-5-三氟 甲基-嘧啶-4-基胺基]-甲基卜苯甲基）-膦酸二甲酯； 5 - {4-[(D比陡-2-基甲基）-胺基]-5_三氟甲基-嘧U定-2-基胺基二氫-吲哚-2-酮； -77- 200539871 (75) 5 - [5 -三氟甲基- 4- (2-三氟甲基-苯甲胺基）_嘧卩定-2-基胺基]-1,3 -二氫-D引D朵-2-酮； 5-[4-(3-乙磺醯基-苯甲胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3 -二氫-D引U朵-2-酮； 5-{4-[(嘧B定-2-基甲基）-胺基]-5 -三氟甲基-喃卩定- 2 -基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(卩ϋ曝-2 -基甲基）-胺基]-5 -三氣甲基-嘧Π定-2 -基胺基卜1,3 -二氫- Π〗丨Π朵-2 -酮； Ν-（4 -氟- 3- {[2-(2 -酮- 2,3 -二氫-1H-D引 D朵-5-基胺基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-Ν-甲基-甲磺 醯胺； 5 - {4-[(啦11定-3-基甲基）-胺基]-5 -三氟甲基-嘧Π定-2-基胺基}-1，3 -二氫-吗丨D朵-2-酮； 5 - {4-[(6_甲磺醯基-吡啶-2-基甲基）-胺基]_5_三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(2_甲磺醯基甲基-噻唑-4-基甲基）-胺基]-5-三 氟甲基-嘧、Π定-2-基胺基卜1,3 -二氫-D引D朵-2 -酮； 5 - {4-[(5-甲磺醯基-吡啶_3_基甲基）-胺基]_5_三氟甲 基-喷Π定-2-基胺基}-1,3 -二氫-D引H朵-2-酮； 5 - {4_[(3 -甲基-噻吩-2-基甲基）-胺基]_5_三氟甲基-嘧U定-2-基胺基丨-1,3 -二氫-B引Π朵_2_酮； 5 - {4_[(1H-咪唑-2-基甲基）-胺基]- 5-三氟甲基-嘧啶-2-基胺基卜1,3 -二氫-吲哚-2-酮； N-甲基-N-(3-{[2-(2_ 酮- 2,3-二氫-1H-吲哚 _5-基胺 -78- 200539871 (76) 基）-5-三氟甲基-嘧啶_4_基胺基]-甲基卜苯基）-甲磺醯胺 5 - [4-(2 -甲磺醯基-苯甲胺基）-5-三氟甲基-嘧啶_2 -基胺基]_1，3-二氫-吲哚-2-酮； N -（2-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； ?\1-甲基-1^-(2-{[2-(2-酮-2,3-二氫-1^^-〇引卩朵-5_基胺 基）-5 -三氟甲基-嘧陡-4-基胺基]-甲基}-苯基）-甲磺酿胺 5-{4-[(1，5-二甲基-1H-吡唑-3-基甲基）-胺基]-5-三 氟甲基-嘧B定-2-基胺基}-1,3_二氫-D引P朵-2-_ ; 5-[4-(2-咪唑-1-基-乙胺基）-5_三氟甲基-嘧啶-2-基 胺基]-1,3 -二氫-D引D朵-2 -酮； N -（5_ 甲基 _2-{[2-(2_ 酮- 2,3 -二氫-1H -卩引 D朵-5 -基胺 基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 f 5_{4- [(3 -甲基-卩比Π定-2-基甲基）-胺基]-5 -三氟甲基-赔Π定-2-基胺基}-1，3_二氫-D引D朵-2-酮； 5 一 [4-(3-甲磺醯基-苯甲胺基）-5-三氟甲基-嘧啶-2-基胺基]-1，3-二氫-吲哚-2-酮； 5 - {4-[(異色滿-1-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1，3_二氫-D引D朵-2 -酮； 5-{4-[2_(吡啶-3-基氧基）-丙胺基]-5_三氟甲基-嘧 Π定- 2 -基胺基} - 1，3 -二氫-吲D朵-2 -酮； -79- 200539871 (77) 5-{4-[2-(6 -甲基-卩比卩定-2-基）-乙胺基]-5-三氟甲基-喃H定-2 _基胺基} - 1，3 -二氫-D引D朵-2 -酮； 5-{4-[(2,3-二氫-苯並[1,4]二氧雜環己二烯-2-基甲 基卜胺基]_5_三氟甲基-喃D定-2 -基胺基卜1,3-二氫-D引0朵-2_酮； 5-{4-[2-(4 -甲基-1H-咪哗-2-基）-乙胺基]三氟甲 基-嘧Π定-2-基胺基}-1,3 -二氫-D引D朵-2 -酮； 5-{4-[2-(1Η -苯並咪哗-2-基）_乙胺基]-5 -三鎮甲基-嘧Π定-2-基胺基卜1,3 -二氫-D引D朵-2-酮； 5 - {4_[(5-苯基-4H-[1，2,4]三唑-3-基甲基）-胺基]-5-三氟《甲基-嘧卩定-2-基胺基}-1,3_二氫-卩引D朵-2-酮； 5-{4-[(3_甲基-咪唑並[2,1-b]噻唑-6-基甲基）-胺基]-5 -三氟甲基-喃Π定-2-基胺基卜1,3 -二氫-卩引D朵-2-酮； N - 甲基-N -（2-甲基 _6 - {[2 -（2-嗣 _2,3-二氯-1H-U引 〇朵 _ 5_基胺基卜5-三氟甲基-嘧啶-4_基胺基]-甲基}-苯基）-甲 磺醯胺； N -（2-甲基-6-{[2-(2 -酮-2,3 -二氫-1H-D 引 D朵 _5 -基胺 基）-5 -三氟甲基-嘧、陡-4-基胺基]-甲基卜苯基）-甲擴醯胺 贅 N-(3 -甲磺醯基胺基-5-{[2_(2 -酮-2,3 -二氫-1H-吲 n朵-5_基胺基）_5_三氟甲基-嘧Π定-4-基胺基]-甲基卜苯基）-甲磺醯胺；及 Ν- 甲基-Ν-(3-{[2-(2 - 酮 _2,3 -二氫-1Η -卩引 D朵-5 -基胺 基）-5 -三氟甲基-嘧淀-4-基胺基]-甲基}_啦陡-2-基）-甲擴 -80- 200539871 (78) 醯胺。 本發明之較佳體系是選自下列之化合物： 5-[4-(3 -甲磺醯基-苯甲胺基）-5-三氟甲基-嘧啶-2 -基胺基]-1 , 3 -二氫-D引D朵-2 -酮； 乙磺酸甲基-{3_[2-(2_酮-2,3 -二氫-1H -卩引D朵_5_基胺 基）-5 -三氟甲基-嘧Π定_4 -基胺基]-丙基卜醯胺； 5 - {4 - [(異色滿-1-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基}-1,3_二氫-D引B朵-2-酮； 5 - {4-[2-(吡啶-3-基氧基）-丙胺基]-5-三氟甲基-嘧 旋-2-基胺基}-1,3 -二氫-D引D朵-2-酮； 3 - {[2-(2 -酮- 2,3 -二氫_1H - D引D朵-5 -基胺基）-5_三氟甲 基-嘧B定-4_基胺基]-甲基卜苯磺醯胺； 5 -{4-[(1-甲擴酿基-呢D定_3_基甲基）-胺基]-5-三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； N -（3-{[2-(2 -酮-2,3 -二氣-1H -卩引卩朵-5 -基胺基）_5 -三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_甲磺醯胺； \-甲基-1^-{2-[2-（2-酮-2,3-二氫-114-卩引11朵-5-基胺基 )-5 -三氟< 甲基-嘧陡-4-基胺基]-乙基卜甲磺醯胺； 5 一 {4-[(4-甲磺醢基-嗎啉-2-基甲基）_胺基]-5 -三氟甲 基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5-[4-(3 -甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧 陡-2-基胺基]-1,3-二氫-吲哚-2-酮； 5 - {4-[(1-甲磺醯基-吡咯烷-3-基甲基）_胺基]_5_三氟 甲基-喃Π定-2 -基胺基卜1,3-二氫-D引D朵-2-酮； -81 - 200539871 (79) 1^-甲基-1^-{3-[2-（2-酮-2,3-二氫-114-13引卩朵-5-基胺基 )-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 5 - {4-[2-(1-甲擴酿基-呢陡_2_基）-乙胺基]-5 -三氟甲 基-嘧U定-2 -基胺基} - 1，3 -二氫-D引D朵-2 _酮； 5_{4_[(4_甲磺醯基-U比D定-2-基甲基）-胺基]-5-三氟甲 基-嘧B定-2-基胺基}-1,3_二氫-D引D朵-2-酮； 5 - [4-(3-異丙氧基-丙胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1,3 -二氫-D引D朵-2-酮； 5 - {4-[(5 -甲基-呋喃-2-基甲基）-胺基]-5 -三戴甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5 - {4-[(雙環[2.2.1]庚_5_嫌-2-基甲基）-胺基]-5 -三氟 甲基-嘧Π定-2-基胺基}-1,3 -二氫-D引D朵-2 -酮； N -（4 -氟- 3- {[2-(2 -酮- 2,3 -二氫-1H-D 引 Π朵-5-基胺基）_ 5-三氟甲基-嘧陡-4-基胺基]-甲基卜苯基）-N -甲基-甲碯 醯胺； 5 - {4-[(1-甲磺醯基-哌啶-3-基甲基）-胺基]-5-三氟甲 基-喃Π定-2-基胺基卜1,3 -二氫-D引D朵-2-酮； 5- {4-[(6-甲磺醯基-吡啶-2-基甲基）-胺基]-5-三氟甲 基-嘧Π定-2 -基胺基} - 1 , 3 -二氫-D引D朵_ 2 -酮； 5 - {4-[(5-甲磺醯基-吡啶-3-基甲基）-胺基]-5-三氟甲 基-嘧η定_ 2 -基胺基} - 1，3 -二氫-吲D朵-2 -酮； 5 - [4-(2 -甲磺醯基-苯甲胺基）-5_三氟甲基-嘧啶-2 -基胺基]_1,3_二氫-D引D朵-2 -酮； 5 - {4-[(1-赌D定-2-基-呢卩定-3-基甲基）-胺基]-5 -三氟 -82· 200539871 (80) 甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 5-{4-[2-(1_甲磺醯基-呢D定-2-基）_乙胺基]-5 -三戴甲 基-喃D定-2-基胺基卜1,3 -二氫-吲D朵-2-酮； 5 - {4_[2-(1-甲磺醯基-呢D定-2 -基）-乙胺基]-5 -三氟甲 基-喃Π定-2 -基胺基卜1,3 -二氫-吲D朵-2-酮； N-(2-{[2-(2 -酮- 2,3 -二氫-1H_P 弓丨 D朵-5-基胺基）_5- 三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； 5-{4-[(1_甲磺_基-卩比略院-2-基甲基）_胺基]-5 -三氟 甲基-嘧U定-2-基胺基}-1,3 -二氫-D引D朵-2 -酮； 1^-甲基-1^-（2-{[2-(2-酮-2,3-二氫-11~1-〇弓丨11朵-5-基胺 基）-5 -三氣甲基-嘧淀-4 -基胺基]-甲基卜苯基）-甲擴醯胺 f N-甲基- N-(2-甲基-6-{[2-(2-酮-2,3-二氫-1H-吲哚-5 -基胺基）-5 -三氟甲基-嘧U定-4-基胺基]-甲基卜苯基）-甲 磺醯胺； 5-[4-(2-羥基-萌滿-1-基胺基）-5-三氟甲基-嘧陡-2-基胺基]-1,3-二氫-吲哚-2-酮； 5-{4-[(1-羥基-環戊基甲基）-胺基]-5-三氟甲基-嘧 H定-2-基胺基}-1，3_二氫-D引Π朵-2-酮； 5-{4-[2-經基-2- (1-甲擴醯基-呢Π定-2-基）-乙胺基]-5 -三氟甲基-嘧Π定-2-基胺基卜1,3 -二氫-卩引卩朵-2-酮； N- 甲基-N-(3-{[2 -（2-_ - 2,3-二氫-1H-卩引卩朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）_甲磺 醯胺。 -83- 200539871 (81) 本發明之一些特別的體系包含下列化合物： N-甲基-N-{3-[({甲基-[2-（2-酮 - 2,3 -二氫-1H-D引 B朵-5 -基胺基）-5 -三氟甲基-嘧B定-4-基]-胺基})-甲基]-苯基}-甲磺醯胺； 1^-甲基-1^_{4-甲基-3-[({甲基-[2-(2-酮-2,3-二氫-1H-D弓| D朵-5-基胺基）一5-三氟甲基一喃Π定-4-基]一胺基})-甲基 ]-苯基卜甲磺醯胺； N -（5 -甲基-2- {[2-(2 -酮-2,3-二氫-1H-D引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醢胺 9 N -（3- 甲基-2- {[2-(2 -酮-2,3-二氫-1H - D引 D朵-5 -基胺 基）_ 5-三氟甲基-嘧啶_4_基胺基]-甲基卜苯基）-甲磺醯胺 > N-（4- 甲基-2-{[2_(2_ 酮 _2,3_ 二氫-1H-D引 D朵-5 -基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 9 N -（2 -甲基-6 - {[2-(2 -酮-2,3 -二氫-1H - D引 D朵-5 -基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺5-{4-[(1,5-Dimethyl-1H-D bis-3-ylmethyl) _amino] -5-trifluoromethyl-pyrimidine, azu-2-ylamino}- 1,3 -Digas-D-D-D-2-one; and 5- [4- (2-imidazol-1-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino ] -1,3 -Dihydro-D Introduce B-2-one. Some of the preferred systems of the present invention are compounds selected from the group consisting of: 5-{4-[(1-methylexpanyl-warmth-3-ylmethyl) -amino] -5 -trifluoromethyl-ran Π 定 -2 -aminoamino group 1,3_dihydro-indodo-2 -one; N-methyl-N- {2_ [2- (2_ ketone-2,3 -dihydro-1H-D D-5-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino] -ethylsulfonylsulfonamide; -73- 200539871 (71) N -methyl-N- { 3- [2- (2-keto-2,3-dihydro-1H-U-n-do-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbenzene Methanesulfonyl amine; 5-{4_ [2_ (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-benzyl-2-ylamino} -1 , 3-Dihydro-D-D-D-2-one; 5-{4 _ [(Bicyclo [2.2.1] heptan-5-yl-2-aminomethyl) -amino] -5-trifluoromethyl -Aran-2-ylaminopyridine 1,3-dihydro-D-Bind-2-one; 5- [4- (3-methyl-butylamino) -5-trifluoromethyl-pyrimidine -2-ylamino] -1,3-dihydro-morpho-2-o-2-one; 5-{4-[(1-methylexpanyl-piperidin-3-ylmethyl) -amine Yl] -5-trifluoromethyl-pyrimidino-2-ylamino} -1,3-dihydro-D-D_2_2one; ^ -isopropyl-1 ^-{3- [2 -(2-keto-2,3-dihydro-11 ~ 1-1-pyridin-5-ylamino) -5- Trimethyl-pyrimidine-4_ylamino] -propyl} -methanesulfonamide; 1 ^ -cyclohexyl-1 ^ _ {3- [2- (2-keto-2,3-dihydro- 11 ^ -pyridine-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutrazinesulfonamide; 5-{4- [2- (1-methyl Sulfonyl-benzyl-2-yl) -ethylamino] -5 -trifluoromethyl-pentin-2-ylamino group 1,3-dihydro-D-D-do-2-one; N-isopropyl-N_ {2- [2- (2-keto-2,3_dihydro-1H-pyridine-5 -ylamino) -5 -trifluoromethyl-pyridine_ 4-Aminoamino] -ethylbuferamine; 5- {4-[(1-methylsulfonyl-pyrrolidin-2-ylmethyl) -amino] -5-trifluoromethylpyrimidine Dian-2-ylaminob, 1,3-dihydro-indodo-2_one; 5- (4-cyclopentylamino-5-trifluoromethyl-pyrimidine-2-ylamine ) _1,3-dihydro-D-H 2 -2 -one; methyl ethanesulfonate- {3- [2- (2-one-2,3-dihydro-1H-indole-5-yl Amine) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamine; -74- 200539871 (72) 2,2,2-tris-N-methyl-N- { 3_ [2- (2_keto-2,3-dihydro-1H-pyridin-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamide > N-methyl- N_ {2_ [2- (2 -keto-2,3 -dihydro_1H-D 5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino] -ethylsulfamerazine; 5- (4-cyclobutylamino-5-trifluoromethyl-pyrimidine -2-ylamino) -1,3-dihydro-D-D-D-2-one; 5-{4- [2- -Yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylaminopyridine 1,3-dihydro-indole-2-one; 3-fluorene- 3_ (3-{[2- (2-keto-2,3, -dihydro-1H-D) -5-trifluoromethyl--5-trifluoromethyl-pyrimidine-4-ylamino] -methyl}-? 11 N-l-yl) -propionitrile; 5-{4-[(1-methyl fluorenyl-threonium-4-ylmethyl) -amino] -5_trifluoromethyl-pyrimidine-2 -Ylamino} -1,3-dihydro-np-do-2-one; 5-{4-[(4-methylsulfonyl-morpholin-2-ylmethyl) -amino] -5- Trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one; 5-{4-[(5-keto-morpholin-2-ylmethyl) -amino group ] -5-trifluoromethyl-pyridine-Did-2-ylaminopyridine-1,3-dihydro-D-D-2-2-one; 5-{4 _ [(bumesylsulfonyl-pyrrolidine- 3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5-[4- (3-isopropyl Oxy-propylamino) -5-trifluoromethyl-rano-D-2-ylamino] -1,3-dihydro- D 2 -ketone; 5-{4-[(adamantane-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro- Indole-2-one;! ^-{2,2-dimethyl-3- [2- (2-one-2,3-dihydro-11 ^ -〇 引 1) dol-5-yl-75 -200539871 (73) Amino group) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylsulforamide; 5- {4-[(1-hydroxy-cyclopentylmethyl) -Amine group] 5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-D-D-2-one; 5-{4-[(4-hydroxy-tetrahydro Pyran-4-ylmethyl) -amino group] _5_trifluoromethyl-heptyl-2-ylamino group 1,3-dihydro-indobor-2-one; 5- {4- [(2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5-[4- (3-Methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-amino-2-pyridine; 5- {4- [ (1-pyrimidin-2_yl-_Did-3-ylmethyl) -amino] -5 -trifluoromethyl-pyridinyl-2 -ylamino}-1, 3 -dihydro -D refers to D-2-2 ketone; 3-[2-(2-keto-2,3 -dihydro-1H-D refers to D-5 -ylamino) _5_trifluoromethyl-pyridine 4-ylamino] -ethyl propionate; 5- {4-[(1-ethyl-5-one-pyrrolidin-3-yl ) -Amino] -5_trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one; 2,1 \ 1-dimethyl-1 ^-{ 2- [2- (2-fluorene-2,3-diamino-11-1-13bendo-5-5-ylamino) -5-trifluoromethyl-pyrimido-4-ylamino] -Ethyl} -butanamine; 2-methoxy-N-methyl-N- {3- [2-(2- axe-2,3-dichloro-1H-D indole-5_ylamine ) -5_trifluoromethyl-pyrimidin-4-ylamino] -propylbutamidine »5-{4_ [2- (1_ethynyl-d-Dyn-2-yl) -ethyl Amine] -5 -trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-; 5-{4-[(1_methylsulfonyl-piperidine -2-ylmethyl) _amino] -5-trifluoromethyl-annidine-2 -ylaminob 1,3-dihydro-indodo-2 -one; -76- 200539871 (74 ) 5- {4-[(l-Methylsulfenyl-? Nidin-3-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylamino}-1, 3 -dihydro-D-D-2 -one; 5-{4-[(1-Hydrandyl-2-yl-denox-3-ylmethyl) -amino] -5 -trifluoromethyl -Pyrimidin-2-ylamino} _1,3-dihydro-D-indol-2-one; 3-{[2- (2-one-2,3-dihydro-1? ^- (0) 11--5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbenzylsulfonamide; N-(3-{[2_ ( 2_ keto-2,3 -dihydro-1H-D D-5-ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonyl Amine; N- (4-methoxy_3-{[2- (2-keto-2,3-dihydro-1H-D-D-5-ylamino) -5-trifluoromethyl- Pyrimidine-4-ylamino] -methyl} -phenyl) -methanefluorenamine; 5-[4- (3- (Methanesulfonylmethyl-benzylamino) -5-trifluoromethyl -Pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; N-methyl_N- (4-methyl-3-{[2 * ~ (2 -fluorene- 2,3-diaza-1H- hydrazone | D-do-5 -ylamino) -5 -trifluoromethyl-pyrimido-4 -ylamino] -methyl} _phenyl) -methanesulfonyl Amine; 5-{4-[(4-methylsulfonyl-pyridin-2-ylmethyl) -amino] -5_trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro -Pyridin-2-one; 5-{4-[(5 -methyl-furan-2-ylmethyl) -amino] -5-trifluoromethyl-ranidine-2-ylamino Bu 1,3 -dihydro-D-introduced B-2-one; (3-{[2- (2-keto-2,3-dihydro-1H-indol-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -methylphenylbenzyl) -dimethylphosphonic acid; 5-{4-[(D than steep-2-ylmethyl) -amino]- 5-trifluoromethyl-pyrimidin-2-ylaminodihydro-indole-2-one; -77- 200539871 (75) 5-[5-trifluoromethyl- 4- (2-trifluoromethyl-benzylamino) _pyrimidin-2-ylamino] -1,3 -dihydro -D-Di-2-one; 5- [4- (3-Ethylsulfenyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3 -di Hydrogen-D-U-D-2-one; 5- {4-[(pyrimidin-2-ylmethyl) -amino] -5 -trifluoromethyl-pyridin-2-ylamino 1,3-dihydro-indole-2-one; 5-{4-[(卩 ϋ Exposure-2 -ylmethyl) -amino] -5 -trifluoromethyl-pyrimidine-2 -yl Amino acid 1,3 -dihydro- Π〗 丨 Π 2 -one; N- (4-fluoro-3 3- {[2- (2-keto-2,3 -dihydro-1H-D) D Do-5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -N-methyl-methanesulfonamide; 5-{4-[(啦11Ade-3-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-? 丨 D-2--2-one; 5- {4-[(6-Methanesulfonyl-pyridin-2-ylmethyl) -amino group] _5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2 -Ketone; 5-{4-[(2-Methanesulfonylmethyl-thiazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidinyl 1,3 -dihydro-D-D-2 -one; 5-{4-[(5-methylsulfonyl-pyridine Pyridinyl_3_ylmethyl) -amino group] _5_trifluoromethyl-pentin-2-ylamino group} -1,3-dihydro-D-H_2-2-one; 5-{4_ [(3-Methyl-thien-2-ylmethyl) -amino group] _5_trifluoromethyl-pyrimidin-2-ylamino group-1,3-dihydro-B Ketone; 5-{4 _ [(1H-imidazol-2-ylmethyl) -amino group] 5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2 -Ketone; N-methyl-N- (3-{[2- (2_ ketone-2,3-dihydro-1H-indole_5-ylamine-78- 200539871 (76) group) -5-tris Fluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine 5-[4- (2-methylsulfonyl-benzylamino) -5-trifluoromethyl- Pyrimidine_2 -ylamino] _1,3-dihydro-indole-2-one; N-(2-{[2- (2-one-2,3-dihydro-1H-indole-5- Methylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide;? \ 1-methyl-1 ^-(2-{[2- (2-keto-2,3-dihydro-1 ^^-〇indo-5-5-ylamino) -5 -trifluoromethyl-pyrimidino-4-ylamino] -methyl} -benzene ) -Methanesulfonylamine 5- {4-[(1,5-Dimethyl-1H-pyrazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -Ylamino} -1,3_dihydro-D-P-2--2-; 5- [4- (2-imidazol-1-yl-ethylamino) -5_ Fluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-2-one; N-(5_methyl_2-{[2- (2_ ketone-2,3- Dihydro-1H-hydrazone-5 -ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine f 5_ {4- [ (3-Methyl-fluorenylidene-2-ylmethyl) -amino] -5 -trifluoromethyl-pentidino-2-ylamino} -1,3-dihydro-D Dor-2-one; 5-mono [4- (3-methylsulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole 2-ketone; 5-{4-[(isochroman-1-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-D D 2 -one; 5- {4- [2_ (pyridin-3-yloxy) -propylamino] -5_trifluoromethyl-pyrimidine-2 -ylamino}-1, 3- Dihydro-indole-2 -one; -79- 200539871 (77) 5- {4- [2- (6- (methyl-pyridin-2-yl) -ethylamino] -5-tri Fluoromethyl-Hydan-2-ylamino} -1,3-dihydro-D-D-2-2-one; 5- {4-[(2,3-dihydro-benzo [1, 4] Dioxane hexadien-2-ylmethylimido] -5_trifluoromethyl-anhydro-2,2-aminoamino 1,3-dihydro-D Ketone; 5- {4- [2- (4-methyl-1H-imidazol-2-yl) -ethylamino] tri Methyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-2-2-one; 5- {4- [2- (1Η-benzimidol-2-yl) _Ethylamino] -5 -tris-methyl-pyrimidin-2-ylaminopyridine 1,3-dihydro-Dendor-2-one; 5-{4 _ [(5-phenyl- 4H- [1,2,4] triazol-3-ylmethyl) -amino] -5-trifluoro [methyl-pyrimidin-2-ylamino} -1,3_dihydro-fluorene Indole-2-one; 5- {4-[(3-methyl-imidazo [2,1-b] thiazole-6-ylmethyl) -amino] -5 -trifluoromethyl-an Π -2--2-aminoamino group 1,3 -dihydro-pyridine D 2-2-one; N-methyl -N-(2-methyl_6-{[2-(2-fluorene_2 , 3-dichloro-1H-U-O_5_ 5-aminoamino group 5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) -methanesulfonamide; N- (2-methyl-6-{[2- (2-keto-2,3 -dihydro-1H-D-D_5 -ylamino) -5 -trifluoromethyl-pyrimidine, steep-4 -Methylamino] -methylphenylphenyl) -methanesulfonylamine N- (3-methylsulfonylamino-5--5-[[2_ (2-keto-2,3-dihydro-1H-ind n_5_ylamino) _5_trifluoromethyl-pyrimidine-4-ylamino] -methylbuphenyl) -methanesulfonamide; and N-methyl-N- (3- {[2- (2-Ketone_2,3 -dihydro-1Η- 卩 DD-5 -ylamino) -5 -trifluoromethyl-pyrimidine 4-ylamino] - methyl} _ steep-2-yl) - A diffuser -80-200539871 (78) Amides. The preferred system of the present invention is a compound selected from the following: 5- [4- (3- (Methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1, 3 -dihydro-D-D-D- 2 -one; methyl ethanesulfonate- {3_ [2- (2_keto-2,3 -dihydro-1H-D-D-_5_ylamino) -5 -trifluoromethyl-pyrimidine-4 -ylamino] -propylbutanamine; 5-{4-[(isochroman-1-ylmethyl) -amino] -5-trifluoro Methyl-pyrimidin-2-ylamino} -1,3-dihydro-D-B-2-one; 5-{4- [2- (pyridin-3-yloxy) -propylamino]- 5-trifluoromethyl-pyrimidino-2-ylamino} -1,3-dihydro-D-D-2-one; 3-{[2- (2 -keto-2,3 -dihydro _1H-D is 5 -ylamino) -5_trifluoromethyl-pyrimidine-4_ylamino] -methylbenzsulfenylamine; 5-{4-[(1- Methano-N-D-D3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one; N -(3-{[2- (2-keto-2,3 -digas-1H-pyridine-5 -ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -formyl Phenylphenyl) -methanesulfonylamine; \ -methyl-1 ^-{2- [2- (2-keto-2,3-dihydro-114-fluorenyl 11-5-ylamino) -5 -trifluoro < methyl-pyrimidino-4-ylamino] -ethyl Sulfamethoxamine; 5-mono {4-[(4-Methanesulfonyl-morpholin-2-ylmethyl) _amino] -5 -trifluoromethyl-pyrimidin-2-ylamino p 1 , 3-dihydro-indole-2-one; 5- [4- (3- (Methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; 5-{4-[(1-methylsulfonyl-pyrrolidin-3-ylmethyl) _amino] _5_trifluoromethyl-an Π 定 -2 -aminoaminob 1,3-dihydro-D-D-2-one; -81-200539871 (79) 1 ^ -methyl-1 ^-{3- [2- (2- Keto-2,3-dihydro-114-13 (trimethyl-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylmethanesulfonamide; 5-{ 4- [2- (1-Methylpyridinyl-neo-2-yl) -ethylamino] -5 -trifluoromethyl-pyrimidine-2 -ylamino}-1,3-dihydro -D-D-2-2 ketone; 5_ {4 _ [(4_methylsulfonyl-U than D-Dio-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -Amino group} -1,3-dihydro-D-D-2-one; 5-[4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2- Aminoamino] -1,3-dihydro-D-D-2-one; 5-{4-[(5-methyl-furan-2-ylmethyl) -amino] -5 -trimethyl -Pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5-{4-[(bis [2.2.1] Hepta-5-yl-2-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidine-2-ylamino} -1,3-dihydro-D Dado-2 -one; N-(4 -fluoro-3-{[2- (2 -one-2,3 -dihydro-1H-D indole-5-ylamino) _ 5-trifluoromethyl -Pyrimidin-4-ylamino] -methylbuphenyl) -N-methyl-formamidine; 5-{4-[(1-methylsulfonyl-piperidin-3-ylmethyl) (Amino) -amino] -5-trifluoromethyl-anhydro-2,2-aminoamino group 1,3-dihydro-D-dod-2-one; 5- {4-[(6-methyl Sulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -ylamino}-1, 3 -dihydro-D ; 5-{4-[(5-methylsulfonyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino}-1, 3- Dihydro-indodol-2 -one; 5-[4- (2-Methanesulfonyl-benzylamino) -5_trifluoromethyl-pyrimidin-2-ylamino] _1,3_di Hydrogen-D-D-D- 2 -one; 5-{4-[(1-bet D-Din-2-yl-nardidine-3-ylmethyl) -amino] -5 -trifluoro-82 · 200539871 (80) Methyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; 5- {4- [2- (1-Methanesulfonyl-N-D-D-2 -Yl) _Ethylamino] -5 -tris-methyl-pyridin-2-ylaminob, 1,3-dihydro-ind D-2-2-one; 5-{4_ [2- (1-Methanesulfonyl-N-Did-2 -yl) -ethylamino] -5 -trifluoromethyl-pyridine-2 -yl Amino group 1,3 -dihydro-indodedo-2-one; N- (2-{[2- (2-keto-2,3 -dihydro-1H_P) 丨 dodo-5-ylamino group ) _5-Trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine; 5- {4-[(1_methylsulfonyl-yl-pyridine) -2- Methyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-2-2-one; 1 ^ -methyl-1 ^-(2-{[2- (2-keto-2,3-dihydro-11 ~ 1-〇 bow 11--5-ylamino) -5 -trisgasmethyl-pyrimido-4- Aminoamino] -methylphenylphenyl) -methaneamine f N-methyl-N- (2-methyl-6-{[2- (2-keto-2,3-dihydro-1H- Indole-5 -ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; 5- [4- (2-hydroxy- Mengman-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; 5- {4-[(1- Hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-indol-2-one; 5- { 4- [2-Cycloyl-2- (1-methylsulfanyl-n-oxid-2-yl) -ethylamino] -5 -trifluoromethyl-pyrimidin-2-ylamino Bu 1,3-dihydro-pyridine-2-one; N-methyl-N- (3-{[2-(2-_-2,3-dihydro-1H-pyridine- 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide. -83- 200539871 (81) Some special systems of the present invention include the following compounds: N-methyl-N- {3-[({methyl- [2- (2-keto-2,3 -dihydro-1H) -D-B 5 -ylamino) -5 -trifluoromethyl-pyrimidin-4-yl] -amino})-methyl] -phenyl} -methanesulfonamide; 1 ^- Methyl-1 ^ _ {4-methyl-3-[({Methyl- [2- (2-keto-2,3-dihydro-1H-D bow | DDO-5-ylamino)) 5-trifluoromethylmonoanidin-4-yl] monoamino})-methyl] -phenylmethanesulfonamide; N-(5 -methyl-2- {[2- (2- Ketone-2,3-dihydro-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonylamine 9 N-(3-methyl-2- {[2- (2-keto-2,3-dihydro-1H-D-D--5-ylamino) _ 5-trifluoromethyl-pyrimidine_ 4-Methylamino] -methylphenylphenyl) -methanesulfonamide > N- (4-methyl-2-{[2_ (2_one_2,3_dihydro-1H-D) 5-methylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide 9 N-(2-methyl-6-{[2- ( 2 -keto-2,3 -dihydro-1H -D-D-5 -ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonate Amidine

I 5 一 [4-(3-甲磺醯基-丙胺基）-5-三氟甲基-嘧啶-2-基 胺基]-1,3 -二氫-D引D朵-2-酮； N - 甲基-N-(5 - 甲基-2_{[2 -（2- 嗣-2,3 - 二氮-1H - D引 D朵-5-基胺基）-5 -三氟甲基- 密D定-4-基胺基]-甲基}-苯基）-甲 磺醯胺； -84- 200539871 (82) N-(3_甲磺醯基胺基-5-{[2-(2 -酮-2,3 -二氫-1H -吲 哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺； N-甲基- N-(4-甲基-2 - {[2 -（2-酮-2,3-二氫-1}^-吲哚-5-基胺基）-5 -三氣甲基-嘧Π定-4-基胺基]-甲基}-苯基）-甲 磺醯胺； N -甲基-N-(2 -甲基-6-{[2 -（2-酮-2,3-二氫-lH-吲哚-5-基胺基）-5-三氟（甲基-喃Π定-4-基胺基]_甲基}-苯基）-甲 磺醯胺； N - 甲基-N -（3- 甲基-2- {[2 -（2- 嗣-2,3-二氮-1H - D 引 B朵-5-基胺基）-5-三氣甲基-嘧陡-4-基胺基]-甲基卜苯基）-甲 磺醯胺； 5- {4-[((IS, 2 R)-2-羥基-環己基甲基）-胺基]-5-三氟甲 基-嘧陡-2-基胺基）-1,3 -二氫-B引D朵-2-酮； 5-[4-((lR,2S)-2-羥基-茚滿-1-基胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮； 5-[4-((S)-l_經甲基-2-苯基-乙胺基）-5-三氟甲基-嘧 陡-2_基胺基]-1,3 -二氫-问丨B朵-2-酮； 1^-（3-(甲擴醯基-甲基-胺基）-5-{[2_(2-酮-2,3-二氫_ 1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜 苯基）_N_甲基-甲磺醯胺； 5-{4-[(1-經基-環戊基甲基）-胺基]-5-三氟甲基-喃 U定- 2 -基胺基丨-1，3 -二氫-吲B朵-2 -酮； N-甲基 _N-(3-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 -85- 200539871 (83) 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶_2_基）-甲磺 醯胺； N -（3-氟- 2-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-苯基）-N-甲基-甲磺 醯胺； 5 - {4-[2-((S)-l-甲磺醯基-吡咯烷-2-基）-乙胺基]- 5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； Φ 5-{4-[(1-羥基-環丁基甲基）-胺基]-5-三氟甲基-嘧 Π定- 2 -基胺基} - 1，3 -二氫-D引D朵-2 _酮； 5 - {4-[2-((R)-1-甲擴醢基-Π比略院-2-基）-乙胺基]- 5-三氟甲基-嘧卩定-2-基胺基}-1,3 -二氫-卩引卩朵-2-酮； N-(2 -氟- 6- {[2-(2 -酮- 2,3 -二氫-1H - D 引 D朵-5-基胺基）-5 -三氣甲基-嘧Π定_4_基胺基]-甲基}-苯基）-N -甲基-甲磺 醯胺； N-(4 -鎮- 2_{[2-(2_ 酮- 2,3-二氫-1H-D 引 D朵-5-基胺基）-® 5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-N-甲基-甲磺 醯胺； N-甲基-N -（4-{[2_(2-酮 -2,3-二氫-1H-吲哚-5-基胺 基）_5-三氟甲基-嘧啶-4-基胺基]-甲基}-吡啶-2-基）-甲磺 醯胺； 1^-{2,2-二甲基-3-[2-(2-酮-2,3-二氫_1!^-卩弓丨11朵-5-基 胺基）-5 -三氟甲基-喃B定-4-基胺基]-丙基卜N-甲基-甲磺 醯胺； N-甲基-N-(6-{[2-(2 -酮-2,3 -二氫-1H -卩引 D朵-5 -基胺 -86- 200539871 (84) 基）-5-三氟甲基-嘧啶-4-基胺基]_甲基卜吡啶-2-基）-甲磺 醯胺； N -（2,4 -二氧 _6_{[2-(2-酮-2,3 -二氫-1H_D 引 D朵-5-基胺 基）-5 -三氟甲基-赌Π定-4-基胺基]-甲基}-苯基）-N -甲基-甲 磺醯胺； 5 - [4-((1R)-1-甲磺醯基-哌啶-3-基胺基）-5-三氟甲 基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮； 1\1-甲基-1^-（6-甲基-3-{[2-（2-醒-2,3-二氫-1^^-卩弓丨11朵-5 -基胺基）_5_三氟甲基-喃陡-4-基胺基]-甲基}-卩比B定-2-基 )-甲磺醯胺； N -甲基-N-(5 - {[2-（2- 酮 - 2,3-二氫-1H -卩引 D朵-5- 基胺 基）-5 -三氟甲基-嘧Π定-4-基胺基]-甲基} - D比Π定-3-基）-甲擴 醯胺； 5 - [4-(1-甲磺醯基-脈Π定-4-基胺基）-5_三鎮甲基-嘧 陡-2-基胺基]-1,3-二氫-D引D朵-2-酮； 5 -{4-[甲基_((R)-1-苯基-乙基）-胺基]_5_三氟甲基-嘧B定-2-基胺基卜1,3 -二氫-D引D杂-2-酮； 5-(4-苯甲胺基-5-三氟甲基-嘧啶-2-基胺基）-1，3-二 氫-吲哚-2-酮； 1^1-（4,6-二甲基-3-{[2-（2-酬-2,3-二氨-1}4-口弓[1]朵-5-基 胺基）~5_三氟甲基-嘧啶-4-基胺基]_甲基}-吡啶-2-基）-N-甲基-甲磺醯胺； 5-(4-第三丁基胺基-5-三氟甲基-嘧啶-2-基胺基）-1，3 -二氫-D引D朵-2 -酮； -87· 200539871 (85) 5 - [4-((lR，5S，6S)-3-甲磺醯基-3-氮雜-雙環[3.1.0] 己-6-基胺基）_5_三氟甲基-嘧啶-2-基胺基]-1,3-二氫-吲 哚-2-酮； N-甲基-N-{3 - 甲基-3 - [2-（2-嗣- 2,3 -二氨-1H-D 引 D朵-5 -基胺基）-5-三氟甲基-嘧D定-4-基胺基]-丁基卜甲磺醯胺 N -（6 -甲基-3- {[2-(2 -酮-2,3 -二氫-1H-D 引 D朵-5-基胺 基）- 5 -三氟甲基-嚼Π定-4-基胺基]-甲基卜卩比11定-2-基）-甲擴 醯胺； 5 - {4-[(2-甲磺醯基-吡啶-4-基甲基）-胺基]-5-三氟甲 基-喃Π定-2 -基胺基} - 1 , 3 -二氫-D引B朵-2 -酮； 2- [2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-喃Π定-4-基胺基]-乙磺酸醯胺； N-(3-{甲基-[2-(2-酮-2,3_二氫-1H-D引 D朵-5- 基胺基）-5 -三氣甲基-喃Π定-4 -基]-胺基}-丙基）-甲擴醯胺； Φ N-(2-{甲基-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）_ 5-三氟甲基-喃Π定-4 -基]-胺基卜乙基）-甲磺醯胺； 5 - [4-(2 -甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧 Π定- 2 -基胺基]-1，3 -二氫-D引D朵-2 -酮； 2 - [2 -（2 -酮- 2,3-二氫-1H-D引B朵-5 -基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-乙磺酸二甲醯胺； 1^-甲基-1^-（3-{[2-（2-酮-2,3-二氫-114-卩引1]朵-5-基胺 基）-5 -三氧甲基-嘧D定-4-基胺基]-甲基卜啦曉-2-基）_甲磺 醯胺； -88- 200539871 (86) 乙磺酸甲基- (2-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 基）-5 -三氟甲基-喃H定-4-基胺基]-甲基卜苯基）-醯胺； 乙磺酸（2-{[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_醯胺； N- 乙基-N-(3-{[2-(2 -酮-2,3 -二氫-1H-D引 D朵-5 -基胺 基）- 5 -三氟甲基-喃Π定-4-基胺基]-甲基卜卩比D定-2-基）-甲磺 醯胺； 1^-{1，1-二甲基_3-[2-(2-酮-2,3-二氫-114-卩弓丨11朵-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； N-(5,6-二甲基- 3-{[2_(2-酮- 2,3-二氫-1H-吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基卜甲基卜吡嗪-2-基）-N-甲基-甲磺醯胺； 5 - {4-[((R)-4_甲擴酿基-嗎啉-3-基甲基）-胺基]-5-三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 丙院-1-擴酸（2-{[2- (2 -酮- 2,3 -二氫-1H - D引卩朵-5-基胺 # 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-醯胺； 5_{4-[2-((R)-4 -甲磺醯基-嗎啉-3 -基）-乙胺基]-5-三 氟甲基—嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 乙磺酸甲基_(3-{[2-(2 -酮- 2,3 -二氫-1H -卩引B朵-5_基胺 基）-5 -三戴甲基-喃Π定-4-基胺基]-甲基}_D比陡-2-基）-醯胺 9 三氟 _N -甲基- N-{3-[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 環丙烷磺酸甲基-{3-[2-(2_酮-2,3-二氫-ΙΗ-吲哚-5- -89 - 200539871 (87) 基胺基）-5_三氟^甲基-喃Π定-4-基胺基]-丙基}-醯胺； 1^-乙基-1^-(2_{[2-（2-酮-2,3-二氫-1}4-卩引卩朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 9 乙磺酸甲基-(5 -甲基-2-{[2-(2-酮-2,3-二氫-1Η-吲 I1朵-5-基胺基）-5-三氟甲基-喃Π定-4-基胺基]-甲基卜苯基）-醯胺； 乙磺酸乙基-（2-{[2-(2_酮- 2,3 -二氫-1H-D引Π朵-5-基胺 基）-5-三氟甲基-嘧啶_4_基胺基卜甲基卜苯基）-醯胺； 乙礎酸乙基-（5 -甲基-2-{[2-(2_酮- 2,3 -二氫-1H -卩引 噪-5-基胺基）-5-三氟甲基-嘧陡-4-基胺基]-甲基卜苯基）-醯胺； N - 乙基-N -（5-甲基-2-{[2 -（2 -醒-2,3 -二氯-1H -卩引 B朵-5 -基胺基）-5 -三氟ί甲基-喃U定-4-基胺基]-甲基卜苯基）-甲 磺醯胺； 乙磺酸（5-甲基-2-{[2-(2-酮-2,3-二氫-1H-吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-苯基）-醯胺； 乙磺酸（3-甲基-2 - {[2-（2-酮-2,3-二氫-1H-吲哚-5-基 胺基）-5 -三氟甲基-嘧、陡-4-基胺基]-甲基}-苯基）-醯胺； 乙擴酸甲基- (3 -甲基-2_{[2-(2 -酮- 2,3 -二氫-1H-D引 哚-5_基胺基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-醯胺； 2-[2_(2-酮-2,3-二氫-114-吲哚-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-乙磺酸甲醯胺； -90· 200539871 (88) 乙磺酸{3-[2-(2 -酮- 2,3 -二氫-1H -卩引卩朵-5-基胺基）-5 -三氟甲基-嘧啶-4-基胺基]-丙基卜醯胺； C-甲磺醯基- N-{3 - [2-（2-酮-2,3-二氫-1}4-吲哚-5-基 胺基）-5 -三氟甲基-嚼Π定-4-基胺基]·•丙基卜甲磺醢胺； 乙磺酸{2-[2-(2-酮- 2,3-二氫_1H_吲哚-5-基胺基）-5 -三氟甲基-嘧啶-4-基胺基]-乙基卜醯胺； C-甲磺醯基-N-{2-[2-(2_酮-2,3-二氫-1H-吲哚-5-基 ^ 胺基）-5 -三氟甲基-喃陡-4-基胺基]-乙基}-甲擴醯胺； 1^-甲基-1^-（4-甲基-3-{[2-(2-嗣-2,3-二氨-1?1-卩弓丨11朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； 5-(4-{[1-(2,2,2 -三氟-乙醯基）-呢陡-3-基甲基]-胺基 }-5-三氣甲基-嘧陡-2-基胺基）-1，3_二氫-D引D朵-2_酮； 2,2,2-三氟-乙磺酸{3-[2-(2-酮-2,3 -二氫-1H -卩引D朵-5 -基胺基）-5-三氟甲基-嘧啶-4 _基胺基]-丙基卜醯胺； N-甲基-（4 - {[2-(2- 酮-2,3_ 二氯-1H -卩引 B朵-5- 基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-2-基）-甲磺 醯胺； N-環丙基-N-（2-{[2-(2-酮-2,3-二氫-1^^-吲哚_5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺； N -甲基-N_(2-{[2-（2-酮-2,3_ 二氫-1H-D 引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基）_甲磺 醯胺； -91 - 200539871 (89) 1^-甲基_1^-(6-{[2-(2-酮-2,3-二氫-1}~1-卩弓丨卩朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基）-甲磺 醯胺； N-甲基- N-(2-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 基）_5_三氟甲基-喃陡-4-基胺基]-甲基卜卩比Π定-3 -基）-甲擴 醯胺； N- 甲基-N- (3-{[2-(2 -酮-2,3 -二氫-1H - D引卩朵 “5 -基胺 # 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-4-基）_甲磺 醯胺； N- 環丙基- N- (3-{[2-(2 -酮- 2,3 -二氣-1H-D引 D朵-5 -基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲 磺醯胺； 1^-甲基-1^-（6-甲基-3-{[2-（2-嗣-2,3-二氫-114-卩引0朵-5 -基胺基）-5 -三氟甲基-嘧H定-4-基胺基]-甲基卜卩比曉-2-基 )-甲磺醯胺； ® 5-{4-[(2-甲磺醯基甲基-吡啶-3-基甲基）-胺基]-5-三 親甲基-嘧陡-2_基胺基卜1,3 -二氫-D引D朵-2-酮； 1^-甲基-1^-(4-{[2-(2-酮-2,3-二氫-114-11弓丨11朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基）-甲磺 醯胺； 1^-甲基_1^-(3-甲基-6-{[2-(2-酮-2,3-二氫-114-13引15朵-5 -基胺基）-5 -三氟甲基-嘧B定-4-基胺基]-甲基丨-卩比Π定-2-基 )-甲磺醯胺； N - 甲基-N -（5 -甲基-3 - {[2 -（2 -嗣 **2,3-二氨-1H - D弓 | D朵- -92· 200539871 (90) 5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-吡啶-2-基 )-甲磺醯胺； ]\1_甲基_1^_(4-甲基_6-{[2-（2_酮-2,3-二氫-11^-〇弓丨卩朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}_吡啶-2-基 )_甲磺醯胺； N-甲基-N -（2-甲基 _5-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧B定-4-基胺基]-甲基定-3-基 •卜甲磺醯胺； N - 甲基-N-(5 - 甲基-6~~{[2 -（2 -嗣 - 2,3-二氨-1H-卩引 Π朵-5 -基胺基）-5 -三氟甲基-嘧陡-4-基胺基]-甲基卜卩比0定-2-基 )-甲磺醯胺； N - 甲基-N -（6 -甲基-2 - {[2 -（2- 嗣-2,3 -二氮-1H - Π弓丨 D朵-5 -基胺基）-5 -三氟》甲基_嘧11定-4-基胺基]-甲基卜卩比淀-3-基 )-甲磺醯胺； N-甲基-N-(5-甲基-2 - {[2 -（2-酮-2,3-二氫-1H-吲哚-^ 5_基胺基）-5 -三氟甲基-喃陡-4-基胺基]-甲基卜嘧Π定-4-基 )-甲磺醯胺； 1^-甲基-1^-（5-甲基-2-{[2-（2-嗣-2,3-二氮-114^引11朵-5 -基胺基）-5 -三氣甲基-喃陡-4-基胺基]-甲基卜卩比Π定-3-基 )-甲磺醯胺； 1^-甲基-1^-(4-甲基-2-{[2-(2-嗣-2,3-二氮-114-卩弓丨[1朵-5 -基胺基）-5-三氣甲基-嘧Π定-4-基胺基]-甲基卜卩比Π定-3-基 )-甲磺醯胺； 1^-甲基-1^-(3-甲基-4-{[2-(2-酮-2,3-二氫-1}~1-〇弓丨噪- -93- 200539871 (91) 5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； N -甲基-N -（5-甲基-4-{[2-（2-酮 - 2,3-二氫-1闩-吲哚-5 -基胺基）-5-三氟甲基-嘧D定-4-基胺基]-甲基卜喃Π定-2-基 )-甲磺醯胺； 1^-甲基-1^-(6-甲基-5-{[2-(2-嗣-2,3-二氮-11_1-0弓丨11朵_ 5 -基胺基卜5_三氟甲基-嘧Π定-4-基胺基]-甲基卜卩比Π定-3-基 # )-甲磺醯胺； N-甲基 _N_(6-甲基-2-{[2 -（2-嗣-2,3-二氮-1H-卩引 H朵-5 -基胺基）-5 -三氣甲基-喃Π定-4-基胺基]-甲基卜嘧、D定-4-基 )-甲磺醯胺； 1^-甲基-1^_(5-甲基-4_{[2-（2-嗣-2,3-二氮-11^-0引11朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； N -甲基-N-(2 -甲基-3-{[2 -（2-酮 ΐ 5 -基胺基）-5-三氟甲基-嘧Β定-4-基胺基]-甲基卜卩比淀-4-基 )-甲磺醯胺； Ν -甲基 *~Ν-(6- 甲基-4- {[2-（2 -嗣-2,3-二氨-1Η-卩引 Β朵-5 -基胺基）-5 -三氟ί甲基-嘧陡-4-基胺基]-甲基卜卩比D定-2-基 )-甲磺醯胺； Ν -甲基-Ν-（5 -甲基-3-{[2_(2-嗣-2,3-二氨-1Η-卩引 Β朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-4-基 )-甲磺醯胺； Ν-甲基-Ν -（5-甲基-6-{[2 -（2-酮-2，3-二氫-1Η-吲哚- •94- 200539871 (92) 5 -基胺基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺； N -甲基-N -（5 -甲基-4-{[2-（2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )-甲磺醯胺； 1\1-甲基-1\1-(6-{[2-(2-酮-2,3-二氫-114-卩引11朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-嘧啶-4-基）_甲磺 #醯胺； 1^-甲基-1^-(6-甲基-4-{[2-（2-嗣-2,3-二氨-11_1-卩弓丨11朵-5 -基胺基）-5 -三氣甲基-嘧陡-4-基胺基]-甲基}-喷陡-2-基 )-甲磺醯胺； 1^-甲基-1^-（2-甲基-4-{[2_(2-嗣-2,3-二氯-114-〇弓丨[1朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )-甲磺醯胺； 1^-甲基-1^_(5-{[2-(2-酮-2,3-二氫-11-1-卩弓丨1^朵-5-基胺 ϋ 基）- 5-三氟甲基-嘧U定-4-基胺基]-甲基卜嘧陡-4-基）-甲磺 醯胺； Ν - 甲基-Ν -（2_ 甲基 - 6_{[2-(2- 嗣 - 2,3- 二氣-1Η -卩引 D朵-5 -基胺基）_ 5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺； Ν-甲基- Ν-(6 -甲基-4 - {[2-(2-酮-2,3-二氫-lH-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )-甲磺醯胺； N-甲基-N-(4-{[2-(2 -酮-2,3-二氫-1H -卩引 D朵-5 -基胺 •95· 200539871 (93) 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-嘧啶_5_基）-甲磺 醯胺； N-甲基-N-(2-甲基 -5-{[2-(2-酮-2,3-二氫-11~1-吲哚-5 -基胺基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺； 1^-甲基-1^-（4-甲基-6-{[2-（2-嗣-2,3-二氫-114-卩弓丨卩朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-5-基 • )_甲磺醯胺； N - 甲基-N -（5- 甲基 - 6_{[2-（2- 酮- 2,3 -二氫-1H-D 弓丨 B朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基 )-甲磺醯胺； N-甲基- N-(5-甲基-3-{[2-(2-酮-2,3-二氫-114-吲哚-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基 )-甲磺醯胺； N -甲基-N-(2- 甲基-6- {[2-（2- 嗣-2,3 -二氮-1H -卩引 B朵-^ 5-基胺基）-5 -三氣甲基-嘧陡-4-基胺基]-甲基}-嘧、陡-5-基 )_甲磺醯胺； N -甲基-N -（3- 甲基 _6 - {[2 -（2 -嗣 - 2,3 -二氨-1H -卩引 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基 )-甲磺醯胺；及 1^-甲基-1^-（6-甲基-5-{[2-(2-嗣_2,3-二氨-11~1-卩引11朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺。 本發明亦有關一種用於治療哺乳動物（包含人類）之異 -96- 200539871 (94) 常細胞生長的方法，其包含予該哺乳動物投服以治療異常 細胞生長有效量之如上所述之式1所示之化合物，或其藥 學上可接受之鹽、溶劑化物或前驅藥物。於此方法之一體 系中，異常細胞生長是癌症，包含（但不限於此）肺癌、骨 癌、胰臟癌、皮膚癌、頭或頸的癌症、皮膚和眼內黑色素 瘤、子宫癌、卵巢癌、直腸癌、肛門部位的癌症、胃癌、 結腸癌、乳癌、子宫癌、輸卵管癌瘤、子宫內膜癌瘤、子 • 宫頸癌瘤、陰道癌瘤、外陰癌瘤、Hodgkin氏疾病、食道 癌、小腸癌、內分泌系統的癌症、甲狀腺癌、副甲狀腺癌 、腎上腺癌、軟性組織肉瘤、尿道癌、陰莖癌‘、前列腺癌 、慢性或急性白血病、淋巴細胞性淋巴瘤、膀胱癌、腎或 輸尿管癌、腎細胞癌瘤、腎盂癌瘤、中樞神經系統（CNS) 的赘瘤、原發性CNS淋巴瘤、脊椎腫瘤、腦幹神經膠瘤、 垂體腺瘤、或上述一或多種癌症之組合。於一體系中，本 發明之方法包含予該哺乳動物投服以治療該癌症實性腫瘤 ^ 有效量之式1所示之化合物。於一較佳體系中，該實性腫 瘤是乳癌、肺癌、結腸癌、腦癌、前列腺癌、胃癌、胰臟 癌、卵巢癌、皮膚癌（黑色素瘤）、內分泌系統的癌症、子 宫癌、睪九癌、和膀胱癌。 於此方法之另一體系中，該異常細胞生長是惡性增殖 性疾病，包含（但不限於此）牛皮癖、惡性前列腺肥大或再 狹窄。 本發明亦有關一種用於治療哺乳動物之異常細胞生長 的方法，其包含予該哺乳動物投服以治療異常細胞生長有 -97- 200539871 (95) 效量之式1所示之化合物，或其藥學上可接受之鹽、溶劑 化物或前驅藥物，以及選自下列的抗腫瘤劑：有絲分裂抑 制劑、烷化劑、抗代謝劑、嵌入性抗生素、生長因子抑制 劑、細胞週期抑制劑、酵素、拓樸異構酶抑制劑、生物反· 應修飾劑、抗體、細胞毒劑、抗荷爾蒙劑、和抗雄激素劑 〇 本發明亦有關一種用於治療哺乳動物（包含人類）之異 • 常細胞生長的藥學組成物，其包含治療異常細胞生長有效 量之如上所述之式1所示之化合物，或其藥學上可接受之 鹽、溶劑化物或前驅藥物，以及藥學上可接受之載體。該 組成物之一體系中，該異常細胞生長是癌症，包含（但不 限於此）肺癌、骨癌、胰臟癌、皮膚癌、頭或頸的癌症、 皮膚和眼內黑色素瘤、子宫癌、卵巢癌、直腸癌、肛門部 位的癌症、胃癌、結腸癌、乳癌、子宫癌、輸卵管癌瘤、 子宫內膜癌瘤、子宫頸癌瘤、陰道癌瘤、外陰癌瘤、 ® Hodgkin氏疾病、食道癌、小腸癌、內分泌系統的癌症、 甲狀腺癌、副甲狀腺癌、腎上腺癌、軟性組織肉瘤、尿道 癌、陰莖癌、前列腺癌、慢性或急性白血病、淋巴細胞性 淋巴瘤、膀胱癌、腎或輸尿管癌、腎細胞癌瘤、腎盂癌瘤 、中樞神經系統（CNS)的贅瘤、原發性CNS淋巴瘤、脊椎 腫瘤、腦幹神經膠瘤、垂體腺瘤、或上述一或多種癌症之 組合。於該藥學組成物之另一體系中，該異常細胞生長是 惡性增殖性疾病，包含（但不限於此）牛皮癣、惡性前列腺 肥大或再狹窄。 -98- 200539871 (96) 本發明亦有關一種用於治療哺乳動物之異常細胞生長 的方法，其包含予該哺乳動物投服以治療異常細胞生長有 效量之式1所示之化合物，或其藥學上可接受之鹽、溶劑 化物或前驅藥物，以及選自下列的抗腫瘤劑：有絲分裂抑 制劑、烷化劑、抗代謝劑、嵌入性抗生素、生長因子抑制 劑、細胞週期抑制劑、酵素、拓樸異構酶抑制劑、生物反 應修飾劑、抗體、細胞毒劑、抗荷爾蒙劑、和抗雄激素劑 • 〇 本發明亦有關一種用於治療異常細胞生長的藥學組成 物，其中該組成物包含治療異常細胞生長有效量之如上所 述之式1所示之化合物，或其藥學上可接受之鹽、溶劑化 物或前驅藥物，以及選自下列的抗腫瘤劑：有絲分裂抑制 劑、烷化劑、抗代謝劑、嵌入性抗生素、生長因子抑制劑 、細胞週期抑制劑、酵素、拓樸異構酶抑制劑、生物反應 修飾劑、抗體、細胞毒劑、抗荷爾蒙劑、和抗雄激素劑。 ® 本發明亦有關一種用於治療哺乳動物（包含人類）之與 血管形成（angiogenesis)有關的疾病之方法，其包含予該 哺乳動物投服以治療該疾病有效量之如上所述之式1所示 之化合物，或其藥學上可接受之鹽、溶劑化物或前驅藥物 ，以及一或多種如上所述之抗腫瘤劑。該疾病包含癌性腫 瘤例如黑色素瘤；眼病例如與年齡有關的黃斑變性、推定 的眼睛組織胞漿菌病徵候群、和由增殖性糖尿病性視網膜 病變所導致的視網膜血管增生；類風濕性關節炎；骨質流 失疾病例如骨質疏鬆、Paget氏病、惡性體液高鈣血症、 -99- 200539871 (97) 由腫瘤轉移至骨的高鈣血症、和由糖皮質激素治療所引發 的骨質疏鬆；冠狀動脈再狹窄；及一些微生物感染包含與 選自下列微生物病原體相關的感染：腺病毒、漢他病毒、 伯氏疏螺旋菌（eor/'d/a 、耶辛尼氏菌 (Yersinia 5·/?/?·)、百日咳桿菌、和 A 群鏈球菌（g r o u p A S t r e p t o c o c c u s)。 本發明亦有關一種用於治療哺乳動物之異常細胞生長 # 的方法（及藥學組成物），其包含一定量之式1所示之化合 物，或其藥學上可接受之鹽、溶劑化物或前驅藥物，及一 定量之一或多種選自抗血管形成劑、訊號轉導抑制劑、及 抗增殖劑之物質，而其量是可一起有效治療該異常細胞生 長者。 抗血管形成劑，例如MMP_2(基質-金屬蛋白酶2)抑制 劑、MMP-9(基質-金屬蛋白酶9)抑制劑、COX-II(環氧合 酶II)抑制劑，可與式1所示之化合物一起倂用於本文所述 • 之方法和藥學組成物。有用的COX-II抑制劑的例子包含 CELEBREX™(celecoxib)、Bextra(valdecoxib)、paracoxib 、Vioxx(rofecoxib)、和 Arcoxia(etoricoxib)。有用的基質- 金屬蛋白酶抑制劑的例子揭示於WO 96/33172(1996年10 月24日公開）、W0 96/27583(1996年3月7日公開）、歐洲專 利申請案97 3049 7 1.1 ( 1 997年7月8日申請）、歐洲專利申請 案 99308617.2(1999年 10月 29 日申請）、W0 98/07697(1998 年2月26日公開）、WO 98/03516(1998年1月29日公開）、 WO 98/34918(1998年 8 月 13 日公開）、WO 98/34915(1998 •100· 200539871 (98) 年8月13日公開）、WO 98/33768(1998年8月6日公開）、WO 98/30566(1998年 7 月 16 日公開）、EP 606,046(1994年 7 月 13 日公開）' EP 93 1,788(1 999年7月28日公開）、WO 9 0/05719(1990年 5 月 31 日公開）、WO 99/52910(1999 年 10 月21日公開）、WO 99/52889(1999年10月21日公開）、WO 99/29667(1 999年6月17日公開）、PCT國際申請案 PCT/IB98/01113(1998年7月21日申請）、歐洲專利申請案 φ 99302232.1(1 999年3月25日申請）、英國專利申請案 9912961.1(19 99年6月3日申請）、美國專利臨時申請案 60/148,464(1999年8月12日申請）、美國專利案 5,86 3,949(1 999年1月26日公告）、美國專利案 5,861,510(1999年 1 月 19 日公告）及 EP 780,386(1997年 6 月 25曰公開）。所有內容均倂入本文以爲參考。較佳的MMP-2和MMP-9抑制劑係爲具有少許MMP-1抑制活性或完全不 具Μ MP-1抑制活性者。更佳的是相對於其他的基質-金屬 φ 蛋白酶抑制劑（即 MMP-1、ΜΜΡ-3、ΜΜΡ-4、ΜΜΡ-5、 ΜΜΡ-6、ΜΜΡ-7、ΜΜΡ-8、ΜΜΡ-10、ΜΜΡ-11、ΜΜΡΊ2 和ΜΜΡ-13)而選擇性抑制ΜΜΡ-2及/或ΜΜΡ-9者。 可與本發明之化合物倂用之Μ Μ Ρ抑制劑的一些特殊例 子是 AG-3340、RO-32-3555、RS - 1 3-0830、及下列化合物 3-[[4-(4-氟-苯氧基）-苯磺醯基]-(1-羥基胺甲醯基-環戊基）_胺基]-丙酸； 3-外-3-[4-(4-氟-苯氧基）-苯磺醯胺基]-8-氧雜-雙環 -101 · 200539871 (99) [3.2.1] 辛烷-3-甲酸羥基醯胺； (2R，3R)l-[4-(2 -氯-4-氟-苄氧基卜苯磺醯基卜3 -羥 基-3-甲基-哌啶-2-甲酸羥基醯胺； 4-[4-(4-氟-苯氧基）-苯磺醯胺基]-四氫-吡喃—4-甲酸 羥基醯胺； 3 - [[4 -（4 -氟-苯氧基）-苯磺酿基]_(1-經基肢甲醯基一 環丁基）-胺基]-丙酸； • 4-[4-(4_氯-苯氧基）-苯磺醯胺基]-四氫-吡喃甲酸 羥基醯胺； 3_[4-(4-氯-苯氧基）-苯磺醯胺基]-四氫-吡喃-3-甲酸 羥基醯胺； (2R,3R)1-[4-(4-氟-2-甲基氧基）-苯磺醯基]—3 一羥 基-3-甲基-哌啶-2-甲酸羥基醯胺； 3-[[4_(4_氟-苯氧基）-苯磺醯基]-(1_羥基胺甲醯基-1-甲基-乙基）-胺基]-丙酸； B 3-[[4_(4-氟-苯氧基）-苯磺醯基]-(4-羥基胺甲醯基- 四氫-吡喃-4-基）-胺基]-丙酸； 3-外-3-[4-(4-氯-苯氧基）-苯磺醯胺基]-8-氧雜-雙環 [3.2.1] 辛烷-3-甲酸羥基醯胺； 3-內-3-[4-(4-氯-苯氧基）-苯磺醯胺基]_8-氧雜-雙環 [3.2.1] 辛烷-3-甲酸羥基醯胺；及 3- [4-(4-氟-苯氧基）-苯磺醯胺基]-四氫-呋喃-3-甲酸 羥基醯胺； 及該化合物之藥學上可接受之鹽、溶劑化物和前驅藥 -102- 200539871 (loo) 物。 VEGF 抑制劑，例如 SU- 11248、SU-5416 和 SU-6668 (Sugen Inc.of South San Francisco, California, USA)，亦 可與式1所示之化合物一起倂用。VEGF抑制劑揭示於，例 如，WO 99/24440( 1 999年5月20日公開）、PCT國際申請案 PCT/IB 99/00 797( 1 999 年 5 月 3 日申請）、WO 95/21613 (1995年8月17日公開）、WO 99/61422(1999年12月2日公開 φ )、USP 5,834,504(1998 年 11 月 10 日公告）、WO 98/50356 (1998 年 11 月 12 日公開）、USP 5,883,113(1999年 3 月 16 日公 告）、1^? 5,886,020(1999年3月23日公告）、1^? 5,792,783(1998年 8 月 11 日公告）、USP 6,653,308(2003 年 11月25日公告）、WO 99/10349(1999年3月4日公開）、WO 97/32856(1997年 9 月 12 日公開）、WO 97/22596(1997年 6 月 26 日公開）、WO 98/54093(1998 年 12 月 3 日公開）、WO 98/02438(1998年 1 月 22 日公開）、WO 99/ 1 6755(1 999年 4 月 • 8日公開）、和WO 98/02437(1998年1月22日公開），其全部 內容均倂入本文以爲參考。其他特殊的VEGF抑制劑的例 子是 IM862(Cytran Inc.of Kirkland, Washington, USA); Avastin，爲一種抗-VEGF單株抗體（Genentech, Inc.of South San Francisco, California);及血管酶（angiozyme)( 一種由 Ribozyme(Boulder, Colorado)和 Chiron(Emeryville， California)所得之合成核酸酶）。 erbB2受體抑制劑’例如 GW-282974(Glaxo Wellcome, pic)和單株抗體 AR-209(Aronex Pharmaceuticals Inc.of -103- 200539871 (101)I 5-[4- (3-methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-one; N -methyl-N- (5 -methyl-2 _ {[2-(2- fluorene-2,3 -diazine-1H-D-D-5-ylamino) -5 -trifluoromethyl -Did-4-ylamino] -methyl} -phenyl) -methanesulfonylamine; -84- 200539871 (82) N- (3-methanesulfonylamino-5-{[2- (2-keto-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonyl Amine; N-methyl-N- (4-methyl-2-{[2-(2-keto-2,3-dihydro-1} ^-indol-5-ylamino) -5 -tri P-methyl-pyrimidine-4-ylamino] -methyl} -phenyl) -methanesulfonamide; N-methyl-N- (2-methyl-6-{[2-(2- Ketone-2,3-dihydro-lH-indole-5-ylamino) -5-trifluoro (methyl-anhydradin-4-ylamino] _methyl} -phenyl) -methanesulfonate Amidoamine; N-methyl-N-(3-methyl-2- {[2-(2-fluorene-2,3-diaza-1H-D) Three-gas methyl-pyrimidino-4-ylamino] -methylbuphenyl) -methanesulfonamide; 5- {4-[((IS, 2 R) -2-hydroxy-cyclohexylmethyl) -Amine] -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-B -2-one; 5- [4-((lR, 2S) -2-hydroxy-indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3 -Dihydro-indole-2-one; 5- [4-((S) -l-methyl-2-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-yl Amine] -1,3 -dihydro-question | B-do-2-one; 1 ^-(3- (methyl fluorenyl-methyl-amino) -5-{[2_ (2-one-2 , 3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) _N_methyl-methanesulfonamide; 5- {4-[(1-Cycloyl-cyclopentylmethyl) -amino] -5-trifluoromethyl-uridine-2 -ylamino 丨 -1,3-dihydro-indB Dado-2 -one; N-methyl_N- (3-{[2- (2-one-2,3-dihydro-1H-indole-5-ylamine-85- 200539871 (83) group) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridine-2-yl) -methanesulfonamide; N-(3-fluoro-2- 2-{[2- (2-one- 2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonate Hydrazine; 5-{4- [2-((S) -1-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino Bu 1,3-dihydro-indole-2-one; Φ 5- {4-[(1-hydroxy-cyclobutylmethyl) -amino] -5-trifluoromethyl -Pyrimidine- 2 -ylamino} -1,3-dihydro-D-D-2 -one; 5-{4- [2-((R) -1-methyl fluorenyl-Π ratio Acryl-2-yl) -ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one; N- ( 2 -fluoro-6- {[2- (2-keto-2,3 -dihydro-1H-D-D-5-ylamino) -5 -trifluoromethyl-pyrimidine_4_yl Amine] -methyl} -phenyl) -N-methyl-methanesulfonamide; N- (4 -zhen-2 _ {[2- (2_ ketone-2,3-dihydro-1H-D) D Dor-5-ylamino) -® 5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -N-methyl-methanesulfonamide; N-methyl-N- (4-{[2_ (2-keto-2,3-dihydro-1H-indole-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyridine -2-yl) -methanesulfonamide; 1 ^-{2,2-dimethyl-3- [2- (2-one-2,3-dihydro_1! ^-卩 弓 丨 11 flowers- 5-ylamino) -5 -trifluoromethyl-an-B--4-ylamino] -propylbenzene N-methyl-methanesulfonamide; N-methyl-N- (6-{[ 2- (2 -keto-2,3 -dihydro-1H -pyridine-5 -ylamine-86- 200539871 (84) yl) -5-trifluoromethyl-pyrimidin-4-ylamino] _Methylpyridin-2-yl) -methanesulfonamide; N-(2,4-dioxo_6 _ {[2- (2-keto-2,3 -di -1H_D D-5-ylamino) -5 -trifluoromethyl-gallidine-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide; 5 -[4-((1R) -1-Methanesulfonyl-piperidin-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-ind Indol-2-one; 1 \ 1-methyl-1 ^-(6-methyl-3-{[2- (2-ake-2,3-dihydro-1 ^^-卩 弓 丨 11 flowers- 5-Methylamino) _5_trifluoromethyl-pyridan-4-ylamino] -methyl} -fluorene than B-Ding-2-yl) -methanesulfonamide; N-methyl-N- ( 5-{[2- (2-Keto-2,3-dihydro-1H-Hydroxy-5-ylamino) -5 -trifluoromethyl-pyrimidine-4-ylamino]- Methyl} -D than hydradinyl-3-methyl) -methanesulfonylamine; 5- [4- (1-methylsulfonyl-methylsulfinyl-4-ylamino) -5-tris-methyl Pyridoxan-2-ylamino] -1,3-dihydro-D-Dind-2-one; 5-{4- [methyl _ ((R) -1-phenyl-ethyl) -amine Group] _5_trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-D-D hetero-2-one; 5- (4-benzylamino-5-trifluoromethyl -Pyrimidin-2-ylamino) -1,3-dihydro-indole-2-one; 1 ^ 1- (4,6-dimethyl-3-{[2- (2-remuneration-2 , 3-Diamino-1} 4-portal bow [1] Duo-5-ylamino) ~ 5_trifluoromethyl-pyrimidin-4-ylamino] _methyl} -pyridin-2-yl -N-methyl-methanesulfonamide; 5- (4-third-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-D -2 -ketone; -87 · 200539871 (85) 5-[4-((lR, 5S, 6S) -3-methanesulfonyl-3-aza-bicyclo [3.1.0] hex-6-ylamine ) _5_trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one; N-methyl-N- {3-methyl-3-[2- (2-fluorene-2,3-diamine-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidinyl-4-ylamino] -butyltrimethanesulfonyl Amine N- (6-methyl-3-{[2- (2-keto-2,3-dihydro-1H-D) N-A-4-ylamino] -methyl-pyridine 11-N-2-yl) -methanefluorenamine; 5-{4-[(2-methylsulfonyl-pyridin-4-ylmethyl)- Amine group] -5-trifluoromethyl-annidine-2 -ylamino group}-1, 3 -dihydro-D-introduction to 2 -2 -one; 2- [2- (2-one-2, 3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-annidine-4-ylamino] -methylsulfonamide; N- (3- {methyl- [2- (2-keto-2,3_dihydro-1H-D-D-5-ylamino) -5 -trifluoromethyl-aminopyridin-4 -yl] -amino} -propyl ) -Methylmethane; Φ N- (2- {methyl- [2- (2-keto-2,3-dihydro-1H-indole-5- Amine group)-5-trifluoromethyl-amino-idin-4 -yl] -aminosulfoethyl) -methanesulfonylamine; 5-[4- (2-methylsulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidine-2 -ylamino] -1,3-dihydro-D-D-2-2-one; 2-[2-(2-one-2,3-di Hydrogen-1H-D-B-5 (5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -dimethylsulfonium ethanesulfonate; 1 ^ -methyl-1 ^-( 3-{[2- (2-keto-2,3-dihydro-114-pyridine 1] do-5-ylamino) -5 -trioxomethyl-pyrimidin-4-ylamino] -Methylbrazol-2-yl) -methanesulfonamide; -88- 200539871 (86) methyl ethanesulfonate-(2-{[2- (2-keto-2,3-dihydro-1H -Indol-5-ylamino) -5 -trifluoromethyl-anhydron-4-ylamino] -methylbuphenyl) -fluorenamine; ethanesulfonic acid (2-{[2- ( 2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -amidine; N -Ethyl-N- (3-{[2- (2-keto-2,3 -dihydro-1H-D-D-5-ylamino)-5 -trifluoromethyl-amino 4-ylamino] -methylpyridine than D-Den-2-yl) -methanesulfonylamine; 1 ^-{1,1-dimethyl_3- [2- (2-one-2,3 -Dihydro-114- 卩 bow 丨 11-5-ylamino group) -5-trifluoromethyl- Pyridin-4-ylamino] -propylmethanesulfonamide; N- (5,6-dimethyl- 3-{[2_ (2-keto-2,3-dihydro-1H-indole- 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylaminomethylmethylpyrazine-2-yl) -N-methyl-methanesulfonamide; 5-{4-[((R ) -4_Methanyl-morpholin-3-ylmethyl) -amino group] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2- Ketones; Glycoin-1-propanoic acid (2-{[2- (2-keto-2,3 -dihydro-1H-D indole-5-ylamine #yl) -5-trifluoromethyl- Pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; 5- {4- [2-((R) -4 -methanesulfonyl-morpholin-3 -yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; methyl ethanesulfonate_ (3-{[2- (2-keto-2, 3 -dihydro-1H -pyridinyl-5 -ylamino) -5 -trimethyl-amino-didin-4-ylamino] -methyl} _D than steep-2-yl) -fluorenamine 9 Trifluoro_N-methyl-N- {3- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Methylamino] -propylmethanesulfonamide; methyl cyclopropanesulfonate- {3- [2- (2_one-2,3-dihydro-l-indol-5--89-200539871 (87) Aminoamino) -5-trifluoro ^ methyl-anidin-4-ylamino]- } -Fluorenamine; 1 ^ -ethyl-1 ^-(2 _ {[2- (2-keto-2,3-dihydro-1} 4-pyridin-5-ylamino) -5 -Trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide 9 methylethanesulfonate- (5-methyl-2-{[2- (2-one- 2,3-dihydro-1fluorene-indioyl-5-ylamino group) -5-trifluoromethyl-anhydroquinidine-4-ylamino group] -methylbuphenyl) -sulfonylamine Ethyl- (2-{[2- (2_keto-2,3 -dihydro-1H-D-indol-5-ylamino) -5-trifluoromethyl-pyrimidine_4_ylamine Benzylmethylphenylphenyl) -fluorenamine; ethyl ethyl- (5-methyl-2-{[2- (2_one-2,3-dihydro-1H-fluorene-5-ylamine) ) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; N-ethyl-N- (5-methyl-2-{[2-( 2 -Xing-2,3 -dichloro-1H -Hydroxymethyl-5 -ylamino) -5 -trifluoromethyl-anuridine-4-ylamino] -methylphenylphenyl) -Methanesulfonamide; ethanesulfonic acid (5-methyl-2-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -methyl} -phenyl) -fluorenamine; ethanesulfonic acid (3-methyl-2-{[2- (2-keto-2,3-dihydro-1H -Indol-5-ylamino) -5 -trifluoromethyl-pyrimidin, 4--4-amino ] -Methyl} -phenyl) -fluorenamine; Ethanoic acid methyl- (3-methyl-2 _ {[2- (2-keto-2,3-dihydro-1H-Dindole-5_ Methylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; 2- [2_ (2-keto-2,3-dihydro-114-ind Indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -formamidine ethanesulfonate; -90 · 200539871 (88) ethanesulfonic acid {3- [2- (2 -Keto- 2,3 -dihydro-1H -pyridin-5-ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -propylbutamidine; C-methanesulfonate Fluorenyl-N- {3-[2- (2-keto-2,3-dihydro-1} 4-indol-5-ylamino) -5 -trifluoromethyl-methyl Propylamino] · • propylmethanesulfonamide; ethanesulfonic acid {2- [2- (2-keto-2,3-dihydro_1H_indol-5-ylamino) -5 -tri Fluoromethyl-pyrimidin-4-ylamino] -ethylpyridamine; C-methanesulfonyl-N- {2- [2- (2-keto-2,3-dihydro-1H-indole) -5-yl ^ amino) -5 -trifluoromethyl-ranox-4-ylamino] -ethyl} -methaneamine; 1 ^ -methyl-1 ^-(4-methyl- 3-{[2- (2- (2- 嗣 -2,3-diamino-1? 1- 卩) 丨 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methylpyridin-2-yl) -methanesulfonamide; 5- (4-{[1- (2,2,2-trifluoro-acetamidine) ) -Nexan-3-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-D-D-2-2one; 2 , 2,2-trifluoro-ethanesulfonic acid {3- [2- (2-keto-2,3-dihydro-1H-pyridine-5 -ylamino) -5-trifluoromethyl- Pyrimidine-4_ylamino] -propylbutamidine; N-methyl- (4-{[2- (2-keto-2,3_dichloro-1H-pyridine) ) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-2-yl) -methanesulfonamide; N-cyclopropyl-N- (2-{[2- (2 -Keto-2,3-dihydro-1 ^^-indole_5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonyl Amine; N-methyl-N_ (2-{[2- (2-keto-2,3_dihydro-1H-D) -D--5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Methylamino] -methylpyrimidin-4-yl) -methanesulfonamide; -91-200539871 (89) 1 ^ -methyl_1 ^-(6-{[2- (2-one-2 , 3-dihydro-1} ~ 1- 卩 bone 丨 卩 -5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -methylpyrazine-2-yl) -Methanesulfonamide; N-methyl-N- (2-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) _5_trifluoromethyl- N-Acet-4-ylamino] -methylbupyridinyl-3 -yl) -mesanamine; N-formamidine -N- (3-{[2- (2-keto-2,3 -dihydro-1H-D) "5-methylamine # group" -5-trifluoromethyl-pyrimidin-4-ylamine [Methyl] -methylpyridin-4-yl) -methanesulfonamide; N-cyclopropyl-N- (3-{[2- (2 -one-2,3 -digas-1H-D Do-5 -ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-( 6-methyl-3-{[2- (2-fluorene-2,3-dihydro-114-fluorene) 0-5 -ylamino) -5 -trifluoromethyl-pyrimidine-4 Propylamino] -methylbupyridyl-2-yl) -methanesulfonylamine; ® 5- {4-[(2-methylsulfonylmethyl-pyridin-3-ylmethyl) -amino group ] -5-Triphilic methyl-pyrimidine-2_ylaminob, 1,3-dihydro-D-D-2-one; 1 ^ -methyl-1 ^-(4-{[2- (2-keto-2,3-dihydro-114-11 bow 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridine-3- ) -Methanesulfonamide; 1 ^ -methyl_1 ^-(3-methyl-6-{[2- (2-one-2,3-dihydro-114-13) 15 -5- Methylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -methyl 丨 -pyridinyl-2-yl) -methanesulfonylamine; N -methyl-N-( 5 -methyl-3-{[2-(2-嗣 ** 2,3-diamino-1H-D bow | D flower--92 · 200539871 (90) 5- Amine) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;] \ 1_methyl_1 ^ _ (4-methyl _6-{[2- (2_one-2,3-dihydro-11 ^ -〇bendo-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} _pyridin-2-yl) _methanesulfonamide; N-methyl-N-(2-methyl_5-{[2- (2-keto-2,3-dihydro-1H -Indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylid-3-yl • methanesulfonamide; N -methyl-N- (5-Methyl-6 ~~ {[2-(2-嗣 -2,3-Diamino-1H-Hydroxy-5-ylamino) -5 -trifluoromethyl-pyrimidine-4 -Methylamino] -methylpyridine-0-demethyl-2-yl) -methanesulfonamide; N -methyl-N-(6-methyl-2-{[2-(2- fluorene-2, 3 -diazine-1H-Π bow D -5 -ylamino) -5 -trifluoro "methyl_pyrimidin-4-ylamino] -methylbupyridine-3-yl) -Methanesulfonamide; N-methyl-N- (5-methyl-2-{[2--(2-keto-2,3-dihydro-1H-indole- ^ 5-ylamino)- 5-trifluoromethyl-pyrido-4-ylamino] -methylpyrimidin-4-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-(5-methyl-2 -{[2- (2-fluorene-2,3-diazine-114 ^ 11 11-5 -ylamino) -5 -trifluoromethyl-anso-4- Amine] -methyl-pyridinium-l-did-3-yl) -methanesulfonylamine; 1 ^ -methyl-1 ^-(4-methyl-2-{[2- (2-fluorene-2, 3-Diazine-114-fluorene 丨 [1 -5 -ylamino] -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbupidinyl-3-yl ) -Methanesulfonamide; 1 ^ -methyl-1 ^-(3-methyl-4-{[2- (2-keto-2,3-dihydro-1} ~ 1-〇 Bow 丨 Noise- -93- 200539871 (91) 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide; N -methyl- N-(5-methyl-4-{[2- (2-keto-2,3-dihydro-1l-indole-5-ylamino) -5-trifluoromethyl-pyridine- 4-ylamino] -methylpropanyl-2-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-(6-methyl-5-{[2- (2-fluorene- 2,3-diaza-11_1-0 bow 11 11_ 5 -aminoamino group 5_trifluoromethyl-pyrimidin-4-ylamino group] -methylbutanidine III group #) -Methanesulfonamide; N-methyl_N_ (6-methyl-2-{[2-(2-fluorene-2,3-diaza-1H-fluorene) ) -5 -Three-gas methyl-anidin-4-ylamino] -methylpyrimidine, D-determinyl-4-methyl) -methanesulfonamide; 1 ^ -methyl-1 ^ _ (5- Methyl-4 _ {[2- (2-fluorene-2,3-diazine-11 ^ -0 leads 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -A Pyridine-2-yl) -methanesulfonamide; N-methyl-N- (2-methyl-3-{[2- (2-ketofluorenyl 5-ylamino) -5-trifluoromethyl -Pyrimidine-4-ylamino] -methylpyridine-4-yl) -methanesulfonamide; N-methyl * ~ N- (6-methyl-4- {[2- ( 2 -fluorene-2,3-diamino-1fluorene-pyridine β-5 -ylamino) -5 -trifluoromethyl-pyrimidino-4-ylamino] -methylbenzene -2-yl) -methanesulfonamide; N-methyl-N- (5-methyl-3-{[2_ (2-fluorene-2,3-diamino-1fluorene-fluorene)-5- Aminoamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-4-yl) -methanesulfonamide; N-methyl-N- (5-methyl-6 -{[2-(2-keto-2,3-dihydro-1fluorene-indole- • 94- 200539871 (92) 5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino ] -Methylpyrimidin-4-yl) -methanesulfonamide; N-methyl-N- (5-methyl-4-{[2- (2-keto-2,3-dihydro-1H- Indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-3-yl) -methanesulfonamide; 1 \ 1-methyl-1 \ 1- (6-{[2- (2-keto-2,3-dihydro-114-pyrene 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) _methanesulfonyl # fluorenamine; 1 ^ -methyl-1 ^-(6- Methyl-4-{[2- (2- 嗣 -2,3-diamino-11_1- 卩 bend 11-11-5-ylamino) -5-trifluoromethyl-pyridine-4-ylamine Group] -methyl} -pentan-2-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-(2-methyl-4-{[2_ (2-fluorene-2,3-di Chloro-114-〇 丨 [1-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-3-yl) -methanesulfonamide; 1 ^ -Methyl-1 ^ _ (5-{[2- (2-keto-2,3-dihydro-11-1-fluorene) ^^-5-ylaminofluorenyl)-5-trifluoro Methyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl) -methanesulfonamide; N -methyl-N-(2-methyl-6-{[2- (2-嗣-2,3-Digas-1Η-卩 D-5 -ylamino) _ 5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl) -formyl Sulfonamide; N-methyl-N- (6-methyl-4-{[2- (2-keto-2,3-dihydro-lH-indole-5-ylamino) -5-tri Fluoromethyl-pyrimidin-4-ylamino] -methylpyridin-3-yl) -methanesulfonamide; N-methyl-N- (4-{[2- (2-one-2,3 -Dihydro-1H-Hydroxy-5-ylamine • 95 · 200539871 (93) group) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyrimidin_5_yl ) -Methanesulfonamide; N-methyl-N- (2-methyl-5-{[2- (2-keto-2,3-dihydro-11 ~ 1-ind Indole-5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-( 4-methyl-6-{[2- (2-fluorene-2,3-dihydro-114-fluorene-1-methyl-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amine] -methylpyrimidin-5-yl •) _methanesulfonamide; N-methyl-N- (5-methyl-6 _ {[2- (2-keto-2,3 -dihydro- 1H-D Bow 丨 B-5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -methylpyrazin-2-yl) -methanesulfonamide; N-formyl -N- (5-methyl-3-{[2- (2-keto-2,3-dihydro-114-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Methylamino] -methylpyrazin-2-yl) -methanesulfonamide; N-methyl-N- (2-methyl-6- {[2- (2-fluorene-2,3- Diazo-1H-hydrazine B-^ 5-ylamino) -5 -trifluoromethyl-pyrimidino-4-ylamino] -methyl} -pyrimidine, steep-5-yl) _methanesulfonate Hydrazine; N -methyl-N-(3-methyl-6-{[2-(2 -fluorene-2,3 -diamino-1H -fluorene D-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -methylpyrazin-2-yl) -methanesulfonamide; and 1 ^ -methyl-1 ^-(6-methyl-5-{[ 2- (2- 嗣 _2,3-diamino-11 ~ 1-pyrene 11 11-5 -ylamino) -5-trifluoromethyl - pyrimidin-4-ylamino] - A Ji Bu 4-yl) - methanesulfonamide Amides. The present invention also relates to a method for treating mammalian (including human) hetero-96-200539871 (94) normal cell growth, which comprises administering to the mammal an effective amount of the above-mentioned formula for treating abnormal cell growth The compound represented by 1, or a pharmaceutically acceptable salt, solvate or prodrug thereof. In one system of this method, the abnormal cell growth is cancer, including (but not limited to) lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, skin and eye melanoma, uterine cancer, ovaries Cancer, rectal cancer, anal cancer, stomach cancer, colon cancer, breast cancer, uterine cancer, fallopian tube cancer, endometrial cancer, sub-cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophageal cancer , Small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer ', prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter Cancer, renal cell carcinoma, renal pyeloma, neoplasm of central nervous system (CNS), primary CNS lymphoma, spinal tumor, brain stem glioma, pituitary adenoma, or a combination of one or more of the above. In one system, the method of the invention comprises administering to the mammal an effective amount of a compound of formula 1 to treat the solid tumor of the cancer. In a preferred system, the solid tumor is breast cancer, lung cancer, colon cancer, brain cancer, prostate cancer, gastric cancer, pancreatic cancer, ovarian cancer, skin cancer (melanoma), endocrine system cancer, uterine cancer, dysentery Nine cancers, and bladder cancer. In another system of this method, the abnormal cell growth is a malignant proliferative disease, including (but not limited to) psoriasis, malignant prostate enlargement, or restenosis. The present invention also relates to a method for treating abnormal cell growth in a mammal, which comprises administering to the mammal an abnormal cell growth-97-200539871 (95) effective amount of a compound represented by Formula 1, or Pharmaceutically acceptable salts, solvates or prodrugs, and antineoplastic agents selected from the group consisting of mitotic inhibitors, alkylating agents, antimetabolites, embedded antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, Topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxic agents, antihormones, and antiandrogens. The present invention also relates to a method for treating differences in mammals (including humans). A pharmaceutical composition comprising an effective amount of a compound represented by Formula 1 as described above, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier for the treatment of abnormal cell growth. In one system of the composition, the abnormal cell growth is cancer, including (but not limited to) lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, skin and eye melanoma, uterine cancer, Ovarian cancer, rectal cancer, cancer of the anus, stomach cancer, colon cancer, breast cancer, uterine cancer, fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophagus Cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter Carcinoma, renal cell carcinoma, pyeloma, tumor of the central nervous system (CNS), primary CNS lymphoma, spinal tumor, brain stem glioma, pituitary adenoma, or a combination of one or more of the above. In another system of the pharmaceutical composition, the abnormal cell growth is a malignant proliferative disease, including (but not limited to) psoriasis, malignant prostate hypertrophy, or restenosis. -98- 200539871 (96) The present invention also relates to a method for treating abnormal cell growth in a mammal, which comprises administering to the mammal an effective amount of a compound represented by formula 1 for treating abnormal cell growth, or a medicament thereof Acceptable salts, solvates or prodrugs, and antineoplastic agents selected from the group consisting of mitotic inhibitors, alkylating agents, antimetabolites, embedded antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, extensions Poisomerase inhibitors, biological response modifiers, antibodies, cytotoxic agents, antihormones, and antiandrogens • The present invention also relates to a pharmaceutical composition for treating abnormal cell growth, wherein the composition comprises a therapeutic An abnormal cell growth effective amount of a compound represented by Formula 1 as described above, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and an antitumor agent selected from the group consisting of a mitotic inhibitor, an alkylating agent, an anti-tumor agent, Metabolic agents, embedded antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological reactions Modifiers, antibodies, cytotoxic agents, antihormones, and antiandrogens. ® The present invention also relates to a method for treating angiogenesis-related diseases in mammals (including humans), comprising administering to the mammal an effective amount of formula 1 as described above The compound shown, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more antitumor agents as described above. The disease includes cancerous tumors such as melanoma; eye diseases such as age-related macular degeneration, putative cytoplasmic disease syndrome of the eye, and retinal vascular hyperplasia caused by proliferative diabetic retinopathy; rheumatoid arthritis ; Bone loss diseases such as osteoporosis, Paget's disease, malignant humoral hypercalcemia, -99- 200539871 (97) hypercalcemia from tumor metastasis to bone, and osteoporosis caused by glucocorticoid therapy; coronal Arterial restenosis; and some microbial infections include infections associated with a microbial pathogen selected from the group consisting of adenovirus, hantavirus, Borrelia burgdorferi (eor / 'd / a, Yersinia 5 · /? /? ·), Pertussis, and group AS treptococcus. The present invention also relates to a method (and pharmaceutical composition) for treating abnormal cell growth # in mammals, which comprises a certain amount of formula 1 The compound shown, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a certain amount of one or more selected from the group consisting of anti-angiogenic agents, No. 1 transduction inhibitor and anti-proliferative agent, and the amount is effective to treat the abnormal cell growth together. Anti-angiogenic agents, such as MMP_2 (matrix-metalloproteinase 2) inhibitor, MMP-9 (matrix- Metalloproteinase 9) inhibitors, COX-II (cyclooxygenase II) inhibitors, can be used with compounds of formula 1 for the methods and pharmaceutical compositions described herein. Useful COX-II inhibitors Examples include CELEBREX ™ (celecoxib), Bextra (valdecoxib), paracoxib, Vioxx (rofecoxib), and Arcoxia (etoricoxib). Examples of useful matrix-metalloproteinase inhibitors are disclosed in WO 96/33172 (October 24, 1996 (Published), WO 96/27583 (published on March 7, 1996), European patent application 97 3049 7 1.1 (filed on July 8, 997), European patent application 99308617.2 (filed on October 29, 1999) , WO 98/07697 (published on February 26, 1998), WO 98/03516 (published on January 29, 1998), WO 98/34918 (published on August 13, 1998), WO 98/34915 (1998 • 100 · 200539871 (98) published on August 13, 1998), WO 98/33768 (published on August 6, 1998), WO 9 8/30566 (published on July 16, 1998), EP 606,046 (published on July 13, 1994) 'EP 93 1,788 (published on July 28, 999), WO 9 0/05719 (May 31, 1990 Published), WO 99/52910 (published on October 21, 1999), WO 99/52889 (published on October 21, 1999), WO 99/29667 (published on June 17, 1999), PCT International Application Case PCT / IB98 / 01113 (filed on July 21, 1998), European patent application φ 99302232.1 (filed on March 25, 1999), UK patent application 9912961.1 (filed on June 3, 1999), United States Provisional Patent Application 60 / 148,464 (filed on August 12, 1999), US Patent 5,86 3,949 (published on January 26, 1999), US Patent 5,861,510 (published on January 19, 1999), and EP 780,386 (published on June 25, 1997). All content is incorporated herein by reference. The preferred MMP-2 and MMP-9 inhibitors are those which have little or no MMP-1 inhibitory activity. Better than other matrix-metal φ protease inhibitors (ie MMP-1, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, MMP-10, MMP -11, MMP-2 and MMP-13) while selectively inhibiting MMP-2 and / or MMP-9. Some specific examples of M MP inhibitors that can be used with the compounds of the present invention are AG-3340, RO-32-3555, RS-1 3-0830, and the following compounds 3-[[4- (4-fluoro- Phenoxy) -benzenesulfonyl]-(1-hydroxyaminomethylmethyl-cyclopentyl) _amino] -propionic acid; 3-exo-3- [4- (4-fluoro-phenoxy) -Benzenesulfonamido] -8-oxa-bicyclo-101 · 200539871 (99) [3.2.1] octane-3-carboxylic acid hydroxyamidoamine; (2R, 3R) l- [4- (2-chloro 4-Fluoro-benzyloxybenzylsulfonyl 3-Hydroxy-3-methyl-piperidine-2-carboxylic acid hydroxylamidine; 4- [4- (4-fluoro-phenoxy) -benzenesulfonate Sulfonylamino] -tetrahydro-pyran-4-carboxylic acid sulfonylamine; 3-[[4-(4-fluoro-phenoxy) -benzenesulfonyl] _ (1- via a methylamidomethyl ring Butyl) -amino] -propionic acid; 4- [4- (4-chloro-phenoxy) -benzenesulfonamido] -tetrahydro-pyranoic acid hydroxyamidoamine; 3_ [4- (4 -Chloro-phenoxy) -benzenesulfonamido] -tetrahydro-pyran-3-carboxylic acid hydroxyamidoamine; (2R, 3R) 1- [4- (4-fluoro-2-methyloxy) -Benzenesulfonyl] -3 monohydroxy-3-methyl-piperidine-2-carboxylic acid hydroxyfluorenamine; 3-[[4_ (4_fluoro-phenoxy) -benzenesulfonyl]-(1_ Hydroxyamine formamidine-1-methyl-ethyl) -amine Group] -propionic acid; B 3-[[4_ (4-fluoro-phenoxy) -benzenesulfonyl]-(4-hydroxyaminomethylmethyl-tetrahydro-pyran-4-yl) -amino ] -Propionic acid; 3-exo-3- [4- (4-chloro-phenoxy) -benzenesulfonamido] -8-oxa-bicyclo [3.2.1] octane-3-carboxylic acid hydroxylamidine Amines; 3-endo-3- [4- (4-chloro-phenoxy) -benzenesulfonamido] -8-oxa-bicyclo [3.2.1] octane-3-carboxylic acid hydroxyamidoamine; and 3 -[4- (4-fluoro-phenoxy) -benzenesulfonamido] -tetrahydro-furan-3-carboxylic acid hydroxyamidine; and pharmaceutically acceptable salts, solvates and prodrugs of the compound- 102-200539871 (loo). VEGF inhibitors, such as SU-11248, SU-5416, and SU-6668 (Sugen Inc. of South San Francisco, California, USA), can also be used with compounds of formula 1 VEGF inhibitors are disclosed in, for example, WO 99/24440 (published May 20, 1999), PCT international application PCT / IB 99/00 797 (filed May 3, 1999), WO 95/21613 (Published on August 17, 1995), WO 99/61422 (published on December 2, 1999), USP 5,834,504 (published on November 10, 1998), WO 98/50356 (published on November 12, 1998) , USP 5,8 83,113 (announced on March 16, 1999), 1 ^? 5,886,020 (announced on March 23, 1999), 1 ^? 5,792,783 (announced on August 11, 1998), USP 6,653,308 (announced on November 25, 2003) , WO 99/10349 (published on March 4, 1999), WO 97/32856 (published on September 12, 1997), WO 97/22596 (published on June 26, 1997), WO 98/54093 (1998 Published on December 3), WO 98/02438 (published on January 22, 1998), WO 99/1 6755 (published on April 8, 1999), and WO 98/02437 (January 22, 1998 (Public), the entire contents of which are incorporated herein by reference. Examples of other specific VEGF inhibitors are IM862 (Cytran Inc. of Kirkland, Washington, USA); Avastin, an anti-VEGF monoclonal antibody (Genentech, Inc. of South San Francisco, California); and angiozyme (angiozyme ) (A synthetic nuclease from Ribozyme (Boulder, Colorado) and Chiron (Emeryville, California)). erbB2 receptor inhibitor ’such as GW-282974 (Glaxo Wellcome, pic) and monoclonal antibody AR-209 (Aronex Pharmaceuticals Inc. of -103- 200539871 (101)

The Woodlands, Texas, U S A)和 2 B - 1 (C h i r ο n)，可與式 1 所 示之化合物一起倂用。此類erbB2抑制劑包含Herceptin、 2C4、和pertuzumab。此類erbB2抑制劑包含下列文獻所揭 示者：W0 98/02434(1998年 1月 22 日公開）、WO 99/35 1 46 (1999年7月15日公開）、WO 99/35132(1999年7月15日公開 )' WO 98/02437(1998年 1 月 22 日公開）、WO 97/13760 (1997年4月17日公開）、WO 95/19970(1995年7月27日公開 # )、USP 5,587,458(1 996年 12 月 24 日公告）和 USP 5,877,3 05 (199 9年3月2日公告），其全部內容均併入本文以爲參考。 可用於本發明之erbB 2受體抑制劑亦揭示於19 99年1月27曰 申請之美國專利臨時申請案60/117,341和1999年1月27日 申請之美國專利臨時申請案60/ 1 1 7,346，其全部內容均倂 入本文以爲參考。其他的erbB2受體抑制劑包含TAK -165( 丁 akeda)和 GW - 572016(Glax〇-Wellcome) 〇 多種其他化合物，例如苯乙烯衍生物，亦已經顯示具 • 有酪胺酸激酶抑制性質，且部份酪胺酸激酶抑制劑已經確 認是爲erbB2受體抑制劑。最近，5個歐洲專利申請案，即 EP 0 566 266 A 1 (1 9 9 3 年 1 0 月 2 0 日公開）、EP 0 602 8 5 1 Al(1 994年 6 月 22 日公開）、EP 0 6 3 5 5 0 7 Al(1 995年 1 月 25 日公開）、EP 0 635 498 Al(1 995年1月25日公開）和EP 0 520 722 Al(1992年12月30日公開），係有關一些雙環衍生 物，特別是唯唑啉衍生物，其因具有酪胺酸激酶抑制性質 而具有抗癌性質。此外，世界專利申請案WO 9 2/2 0642 (1 992年11月26日公開）係有關作爲酪胺酸激酶抑制劑之 -104- 200539871 (102) 雙-單環和雙環芳基和雜芳基化合物，其可用於抑制異常 的細胞增殖。世界專利申請案WO 96/ 1 6960(1 996年6月6 日公開）、WO 96/09294(1 996年3月6日公開）、WO 97/30034( 1997年 8 月 21 日公開）、WO 98/02434(1998年 1月 22日公開）、WO 98/02437(1998年1月22日公開）、和WO 98/024 3 8(1 998年1月22日公開）亦有關用於相同目的之作 爲酪胺酸激酶抑制劑之經取代的雙環雜芳族衍生物。其他 Φ 有關抗癌化合物的專利申請案是WO 00/44728(2000年8月 3日公開）、EP 1 029853A1 (2000年8月23日公開）、和WO 01/98277(2001年12月12日公開），其全部內容均倂入本文 以爲參考。 可與本發明之化合物一起倂用之其他抗增殖劑包含法 呢基蛋白質轉形酶和受體酪胺酸激酶PDGFr之抑制劑，包 含下列美國專利申請案所揭示和請求專利之化合物： 09/221946(1998年 12月 28日申請）；09/454058(1999年 12 Φ 月 2日申請）；09/501163(2000年 2月 9 日申請）；09/53 99 30 (2000年3月31日申請）；09/202796(1997年5月22日申請）； 09/384339(1999 年 8 月 26 日申請）；和 09/383755(1999 年 8 月26日申請）；及下列美國臨時專利申請案所揭示和請求 專利之化合物：60/168207(1999年11月30日申請）； 60/170119(1999 年 12 月 10 日申請）；60/177718(2000年 1 月 21日申請）；60/1 682 1 7 (1 999年11月30日申請）；和 6 0/2 0 0 834 (2 0 00年5月1日申請）。上述美國專利申請案和 美國臨時專利申請案之內容完全倂入本文以爲參考。 -105- 200539871 (103) 式1所示之化合物亦可與其他之可用於治療異常細胞 生長或癌之藥物一起倂用，該藥物包含（但不限於此）可增 進抗腫瘤免疫反應的藥物，例如CTLA4(細胞毒性淋巴細 胞抗原4)抗體和其他可阻斷CTLA4的藥物；及抗增殖劑例 如其他的法呢基蛋白質轉形酶抑制劑，例如上文中之“先 前技術”部份中所引用的文獻中所揭示之法呢基蛋白質轉 形酶抑制劑。可用於本發明之特定的CTLA4抗體包含揭示 9 於美國臨時專利申請案60/113,647(1998年12月23日申請） 所揭示者，其全部內容均倂入本文以爲參考。 式1所示之化合物可以單一治療劑的形式使用，或可 與一或多種其他的抗腫瘤物質倂用，該其他的抗腫瘤物質 是選自，例如，有絲分裂抑制劑（例如V i n b 1 a s t i n e);燒化 劑（例如順銷（cis-platin)、oxaliplatin、卡銷（carboplatin) 和環磷醯胺（cyclophosphamide));抗代謝劑（例如5-氟尿嘧 啶、capecitabine、阿拉伯糖胞苷和羥基脲，或，例如， ^ 歐洲專利案239362所揭示之較佳的抗代謝劑之一，例如 N -（5-[N -（3,4-二氫-2-甲基-4-酮〇奎唑啉-6-基甲基）-?^-甲 胺基]-2-噻吩甲醯基）-L-榖胺酸）；生長因子抑制劑；細 胞週期抑制劑；嵌入性抗生素（例如阿黴素（adriamycin)和 博萊黴素（bleomycin));酵素（例如干擾素）；和抗荷爾蒙劑 (例如抗雌激素劑，例如，Nolvadex(tamoxifen)或，例如， 抗雄激素劑，例如Casodex(4’_氰基-3-(4-氟苯磺醯基）-2-羥基-2-甲基- 3’-(三氟甲基）丙醯替苯胺））。 本發明之化合物可單獨使用或與一或多種不同抗腫瘤 •106- 200539871 (104) 劑或支持治療劑倂用。例如，本發明之化合物可與胞毒劑 一起使用，例如一或多種選自喜樹鹼（camptothecin)、 irinotecan HCl(Camptosar) 、 edot ecarin 、 SU-1 1248 、 epirubicin(Ellence) 、 docet axel(Taxotere)、紫杉醇（ paclitaxel)、rituximab(Rituxan)、bevacizumab(Avastin)、 imatinib 甲擴酸鹽（Gleevac)、Erbitux、gefitinib(Iressa)、 及其組合之物質。本發明亦包含本發明之化合物與荷爾蒙 ® 治療劑倂用，而該荷爾蒙治療劑是例如exemestane (Aromasin)、Lupron、anastrozole(Arimidex)、tamoxifen 檸檬酸鹽（Nolvadex)、Trelstar、及其組合。此外，本發明 提供一種本發明之化合物單獨或與一或多種支持治療產物 倂用之組合物，而該支持治療產物是例如選自Filgrastim (Neupogen)、 ondansetron(Zofran)、 Fragmin、 Procrit 、The Woodlands, Texas, U.S.A. and 2 B-1 (C h i r ο n) can be used together with the compound shown in Formula 1. Such erbB2 inhibitors include Herceptin, 2C4, and pertuzumab. Such erbB2 inhibitors include those disclosed in WO 98/02434 (published on January 22, 1998), WO 99/35 1 46 (published on July 15, 1999), WO 99/35132 (July 1999 (Published on May 15) 'WO 98/02437 (published on January 22, 1998), WO 97/13760 (published on April 17, 1997), WO 95/19970 (published on July 27, 1995), USP 5,587,458 (announced December 24, 996) and USP 5,877,3 05 (announced March 2, 1999), the entire contents of which are incorporated herein by reference. The erbB 2 receptor inhibitors that can be used in the present invention are also disclosed in US Patent Provisional Application 60 / 117,341 filed on January 27, 1999 and US Patent Provisional Application 60/1 1 7,346 filed on January 27, 1999 , The entire contents of which are incorporated herein by reference. Other erbB2 receptor inhibitors include TAK-165 (butakeda) and GW-572016 (Glax〇-Wellcome). Many other compounds, such as styrene derivatives, have also been shown to have tyrosine kinase inhibitory properties. And some tyrosine kinase inhibitors have been identified as erbB2 receptor inhibitors. Recently, 5 European patent applications, namely EP 0 566 266 A 1 (published on October 20, 1993), EP 0 602 8 5 1 Al (published on June 22, 994), EP 0 6 3 5 5 0 7 Al (published on January 25, 1995), EP 0 635 498 Al (published on January 25, 1995) and EP 0 520 722 Al (published on December 30, 1992), It is related to some bicyclic derivatives, especially oxazoline derivatives, which have anticancer properties due to their tyrosine kinase inhibitory properties. In addition, the world patent application WO 9 2/2 0642 (published November 26, 992) is related to -104- 200539871 (102) bi-monocyclic and bicyclic aryl and heteroaryl as tyrosine kinase inhibitors Compounds, which can be used to inhibit abnormal cell proliferation. World patent applications WO 96/1 6960 (published on June 6, 996), WO 96/09294 (published on March 6, 996), WO 97/30034 (published on August 21, 1997), WO 98/02434 (published on January 22, 1998), WO 98/02437 (published on January 22, 1998), and WO 98/024 3 8 (published on January 22, 1998) are also used for the same purpose It is a substituted bicyclic heteroaromatic derivative as a tyrosine kinase inhibitor. Other patent applications related to anticancer compounds are WO 00/44728 (published August 3, 2000), EP 1 029853A1 (published August 23, 2000), and WO 01/98277 (December 12, 2001 (Public), the entire contents of which are incorporated herein by reference. Other antiproliferative agents that can be used with the compounds of the present invention include inhibitors of farnesyl protein transformase and receptor tyrosine kinase PDGFr, including compounds disclosed and claimed in the following U.S. patent applications: 09 / 221946 (filed on December 28, 1998); 09/454058 (filed on December 2, 1999); 09/501163 (filed on February 9, 2000); 09/53 99 30 (31 March 2000) Applications); 09/202796 (filed on May 22, 1997); 09/384339 (filed on August 26, 1999); and 09/383755 (filed on August 26, 1999); and the following U.S. provisional patent applications Compounds disclosed and claimed: 60/168207 (filed on November 30, 1999); 60/170119 (filed on December 10, 1999); 60/177718 (filed on January 21, 2000); 60/1 682 1 7 (application on November 30, 1999); and 6 0/2 0 0 834 (application on May 1, 2000). The contents of the aforementioned U.S. patent applications and U.S. provisional patent applications are fully incorporated herein by reference. -105- 200539871 (103) The compound represented by formula 1 can also be used together with other drugs that can be used to treat abnormal cell growth or cancer. The drug includes, but is not limited to, drugs that can improve the anti-tumor immune response. Examples include CTLA4 (cytotoxic lymphocyte antigen 4) antibodies and other drugs that block CTLA4; and antiproliferative agents such as other farnesyl protein transformase inhibitors, such as those cited in the "Prior Art" section above The farnesyl protein transformase inhibitors disclosed in the literature. Specific CTLA4 antibodies useful in the present invention include those disclosed in US Provisional Patent Application 60 / 113,647 (filed on December 23, 1998), the entire contents of which are incorporated herein by reference. The compound represented by Formula 1 may be used in the form of a single therapeutic agent or may be used with one or more other antitumor substances selected from, for example, a mitotic inhibitor (for example, Vinb 1 astine). Calcining agents (such as cis-platin, oxaliplatin, carboplatin, and cyclophosphamide); anti-metabolites (such as 5-fluorouracil, capecitabine, arabinocytidine, and hydroxyurea, Or, for example, ^ one of the preferred anti-metabolites disclosed in European Patent No. 239362, such as N- (5- [N-(3,4-dihydro-2-methyl-4-one-4-quinazoline) -6-ylmethyl)-? ^-Methylamino] -2-thienylmethylamidino) -L-amidino)); growth factor inhibitors; cell cycle inhibitors; embedded antibiotics (such as doxorubicin ( adriamycin) and bleomycin); enzymes (such as interferon); and antihormones (such as anti-estrogens, such as Nolvadex (tamoxifen) or, for example, anti-androgens, such as Casodex (4'_ Cyano-3- (4-fluorobenzenesulfonyl) -2-hydroxy-2-methyl-3 '-(trifluoromethyl) propanil )). The compounds of the invention can be used alone or in combination with one or more different antitumor agents. 106-200539871 (104) agents or supportive agents. For example, the compounds of the present invention can be used with cytotoxic agents, such as one or more selected from camptothecin, irinotecan HCl (Camptosar), edot ecarin, SU-1 1248, epirubicin (Ellence), docet axel (Taxotere) , Paclitaxel, rituximab (Rituxan), bevacizumab (Avastin), imatinib methoate (Gleevac), Erbitux, gefitinib (Iressa), and combinations thereof. The present invention also includes a compound of the present invention and a hormonal therapeutic agent, such as exemestane (Aromasin), Lupron, anastrozole (Arimidex), tamoxifen citrate (Nolvadex), Trelstar, and combinations thereof. In addition, the present invention provides a composition of the present invention, alone or in combination with one or more supportive treatment products, and the supportive treatment product is, for example, selected from Filgrastim (Neupogen), ondansetron (Zofran), Fragmin, Procrit,

Aloxi、Emend、或其組合之產品。此種聯合治療可利用同 時、先後或分別投服各別治療成份之方式而達成。 本發明之化合物可與抗腫瘤劑、烷化劑、抗代謝劑、 抗生素、由植物衍生的抗腫瘤劑、喜樹鹼（camptothecin) 衍生物、酪胺酸激酶抑制劑、抗體、干擾素、及/或生物 反應改良劑一起使用。因此，以下是可與本發明之化合物 倂用之第二試劑之非限定的例子。 •烷化劑包含（但不限於）氮芥氣N-氧化物、環磷醯胺 、 ifosfamide 、 melphalan 、 busulfan 、 mitobronit 〇1 、 carboquone 、 thiot epa 、 r animustine 、 nimustine 、 temozolomide 、 AMD-473 、 altretamine 、 AP - 5280 、 •107- 200539871 (105) apaziquone、brostallicin、bendamustine、 carmustine、 estramustine、fotemustine、glufosfamide、ifosfamide、 KW-2170、mafosfamide、和 mitolactol;銷配位的院化劑 包含（但不限於）順舶（cis-platin)、卡銷（carboplatin)、 eptaplatin、lobaplatin、奈達銷（nedaplatin)、oxaliplatin 、或 satrplatin ; •抗代謝劑包含（但不限於）methotrexate、6 -硫基嘌 • 呤核糖核苷、毓基嘌玲、5-氣尿嘧陡（5-FU)單獨或與 leucovorin 倂用、tegafur 、 UFT 、去氧氟j 尿苷（ doxifluridine) 、 carmofur 、 cytarabine 、 cy t arabine ocfosfate、enocitabine、S -1、gemcit abine、fludarabine 、5-氮雜胞喃陡核普、c a p e c i t a b i n e、c 1 a d r i b i n e、 clofarabine、decitabine、efl ornithine、乙炔胞嘧 B定核苔 、阿拉伯糖胞脊、經基腺、TS-1、melphalan、nelarabine 、 nolatrexed 、 ocfosfate 、 premetrexed 二納鹽 、 • pentostatin、pelitrexol、ralt itrexed、triapine、 trimetrexat e、vi d arabine、vincristine、vinorelbine ；或 例如，歐洲專利案239362所揭示之較佳的抗代謝劑中之一 ，例如N-(5 - [N -（3,4-二氫-2_甲基-4-酮卩奎唑啉-6-基甲基 )-N-甲胺基]-2-噻吩甲醯基）_L-榖胺酸； •抗生素包含（但不限於）阿克拉黴素（aclarubicin)、 放線菌素 D (a c t i η 〇 m y c i n D)、a m r u b i c i η、a η n a m y c i η、博萊 黴素（bleomycin)、柔紅黴素（daunorubicin)、阿黴素 (doxorubicin)、 el s amitru cin、epirubicin、gal ar u b i cin、 -108· 200539871 (106) 脫甲氧柔紅黴素（idarubicin)、絲裂黴素CUitomycin C)、 nemorubicin、neocarzinostatin、培洛黴素（peplomycin)、 pirarubicin、rebeccamycin、stimalamer、s trept ozocin、 valrubi cin、或 zinostatin ；Aloxi, Emend, or a combination thereof. This combination therapy can be achieved by administering the individual therapeutic components simultaneously, sequentially, or separately. The compounds of the present invention can be used with antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and And / or a biological response modifier. Therefore, the following are non-limiting examples of second reagents that can be used with the compounds of the present invention. • Alkylating agents include (but are not limited to) nitrogen mustard N-oxide, cyclophosphamide, ifosfamide, melphalan, busulfan, mitobronit 〇1, carboquone, thiot epa, r animustine, nimustine, temozolomide, AMD-473, altretamine , AP-5280, • 107- 200539871 (105) apaziquone, brostallicin, bentamustine, carmustine, estramustine, fotemustine, glufosfamide, ifosfamide, KW-2170, mafosfamide, and mitolactol; coordinating chemical agents include (but are not limited to) Cis-platin, carboplatin, eptaplatin, lobaplatin, nedaplatin, oxaliplatin, or satrplatin; • Antimetabolites include (but are not limited to) metotrexate, 6-thiopurine ribose Nucleosides, succinylpurin, 5-FU, alone or in combination with leucovorin, tegafur, UFT, doxifluridine, carmofur, cytarabine, cy t arabine ocfosfate, enocitabine , S -1, gemcit abine, fludarabine, 5-azacytosine steep nuclear nucleus, capecitabine, c 1 adri bine, clofarabine, decapitabine, efl ornithine, acetylene cytosine B nucleating moss, arabinose ridge, transbasal gland, TS-1, melphalan, nelarabine, nolatrexed, ocfosfate, premetrexed dinaline, , Triapine, trimetrexat e, vi d arabine, vincristine, vinorelbine; or, for example, one of the preferred anti-metabolites disclosed in European Patent No. 239362, such as N- (5-[N-(3,4-dihydro -2_methyl-4-ketoquinazoline-6-ylmethyl) -N-methylamino] -2-thienylmethylamino) _L-methylamino acid; • Antibiotics include (but are not limited to) Ah Aclarubicin, acti η ommycin D, amrubici η, a η namyci η, bleomycin, daunorubicin, doxorubicin, el s amitru cin, epirubicin, gal ar ubi cin, -108 · 200539871 (106) demethoxyrubicin (idarubicin), mitomycin CUitomycin C), nemorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin stimalamer, s trept ozocin, valrubi cin, or zinostatin;

•荷爾蒙治療劑是例如exemestane(Aromasin)、 Lupron 、 anastrozole(Arimidex) 、 doxercalciferol 、 fadrozole、formestane、抗-雌激素劑例如 tamoxifen 棒檬 酸鹽（Nolvadex)和 fulvestrant、Trelstar、toremifene .、 raloxifene、1 a s o f o x i f e n e、1 e t r ο z o 1 e (F e m ar a)、或抗-雄激 素劑例如 bicalutamide、flutamide、mifepristone、 nilutamide、Casodex®(4’_氰基- 3-(4-氟苯擴醯基）-2-羥 基-2 -甲基-3’-(三氣甲基）丙醯替苯胺）及其組合； •由植物衍生的抗腫瘤劑包含（但不限於），例如，有 絲分裂抑制劑例如 vinblastine、docetaxel(Taxotere)、和 紫杉醇（paclit axel); •胞毒性拓樸異構酶抑制劑包含一或多種選自阿克拉 黴素（aclarubicin)、bleotecan、喜樹鹼、10-羥基喜樹鹸 、9-胺基喜樹驗、diflomotecan、irinotecan HC1( Camptosar )、edotecarin、epirubicin(Ellence)、etoposide 、exatecan 、 gimatecan 、 lurtotecan 、 mitoxantrone 、 pirarubicin、pixantrone、rubit ecan、sobuzoxane、SN - 38 、tafluposide'和topotecan、及其組合之試劑； •免疫試劑包含干擾素和多種其他的免疫增強劑。干 擾素包含干擾素α、干擾素a-2a、干擾素a_2b、干擾素β -109- 200539871 (107) 、干擾素γ-la或干擾素γ-ηΐ。其他試劑包含filgrastim、 lentinan 、 sizofilan 、 TheraCys 、 ubenimex 、 WF-10 、 aldesleukin 、 alemtuzumab 、 BAM - 002 、 decarbazine 、 daclizumab 、 denileukin 、 gemtuzumab 、 ozogamicin 、 ibrit umomab 、 imiquimod 、 lenograstim 、 lentinan 、 m e 1 a η o m a 疫苗（C o r i x a)、molgramost im、〇ncoVAX-CL、Hormonal therapeutic agents are, for example, exemestane (Aromasin), Lupron, anastrozole (Arimidex), doxercalciferol, fadrozole, formestane, anti-estrogens such as tamoxifen nolvadex and fulvestrant, Trelstar, toremifene., Raloxifene, 1 , 1 etr zo 1 e (F em ar a), or anti-androgen agents such as bicalutamide, flutamide, mifepristone, nilutamide, Casodex® (4'_cyano-3- (4-fluorobenzyl))- 2-hydroxy-2 -methyl-3 '-(trifluoromethyl) propanil aniline) and combinations thereof; • plant-derived antitumor agents include (but are not limited to), for example, mitotic inhibitors such as vinblastine, docetaxel (Taxotere), and paclitaxel (paclit axel); • Cytotoxic topoisomerase inhibitors contain one or more selected from aclarubicin, bleotecan, camptothecin, 10-hydroxycamptothecin, 9 -Aminocampi, diflomotecan, irinotecan HC1 (Camptosar), edotecarin, epirubicin (Ellence), etoposide, exatecan, gimatecan, lurtotecan, mitoxantrone, pirarub icin, pixantrone, rubite ecan, sobuzoxane, SN-38, tafluposide 'and topotecan, and combinations of these reagents; • Immune reagents include interferon and various other immune enhancers. Interferons include interferon α, interferon a-2a, interferon a_2b, interferon β -109- 200539871 (107), interferon γ-la or interferon γ-ηΐ. Other reagents include filgrastim, lentinan, sizofilan, TheraCys, ubenimex, WF-10, aldesleukin, alemtuzumab, BAM-002, decarbazine, daclizumab, denileukin, gemtuzumab, ozogamicin, ib ium, ib mem, ib mem ium, ib membrium (C orixa), molgramost im, oncoVAX-CL,

sargramostim 、 t asonermin 、 tecleukin 、 t hymalasin 、 t ositumomab 、 Virulizin 、 Z -10 0 、 epratuzumab 、 mitumomab、oregovomab、permtumomab、Provenge ； •生物反應改良劑是改良有生命的有機體的防護機制 或生物反應之試劑，例如組織細胞之存活、生長或分化作 用以使組織細胞具有抗腫瘤活性。此類試劑包含krestin、 lentinan、sizofiran、picibanil、或 ubenimex ; •其他抗腫瘤劑包含alitretinoin、ampligen、 atrasentan 、 bexarotene 、 bortezomib 、 bosentan 、 calcitriol、exisulind、finasteride、fotemustine、 ibandronic acid、milt efosine、mit oxantrone、I-天冬醯胺 酶、procarbazine、dacarbazine、羥基脲（ hydroxycarbamide)、pegaspargase、潘司他丁（pentostatin )、tazarotne、TLK-286、Velcade、Tarceva、或 tretinoin •其他抗血管生成的化合物包含acitretin、 fenretinide、thalidomide、zoledronic acid、angiostatin 、apli dine、cilengtide、combret astatin A-4、endostatin •110- 200539871 (108) 、halofuginone ' rebimastat、removal)、Revlimid、角黨胺 (squalamine)、ukrain、和 Vitaxin ； •鈾配位的化合物包含（但不限於）順鉑（cis-platin)、 卡鎖（carboplatin)、奈達鉑（nedaplatin)、或 oxaliplatin ; •喜樹驗衍生物包含（但不限於）喜樹驗、10-羥基喜 樹驗、9-胺基喜樹鹼、irinotecan、SN-38、edotecarin、 及topotecan ;sargramostim, t asonermin, tecleukin, t hymalasin, t ositumomab, Virulizin, Z -10 0, epratuzumab, mitumomab, oregomab, permtumomab, Provenge; • Biological response modifiers are agents that improve the protection mechanism of living organisms or biological reactions For example, the survival, growth, or differentiation of histiocytes can make histiocytes have antitumor activity. Such agents include krestin, lentinan, sizofiran, picibanil, or ubenimex; other anti-tumor agents include alitretinoin, ampligen, atrasentan, bexarotene, bortezomib, bosentan, calcitriol, exisulind, finalideide, fetemustine, ibandronantic acid, mil I-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pegaspargase, pentostatin, tazarotne, TLK-286, Velcade, Tarceva, or tretinoin • Other anti-angiogenic compounds include acitretin, fenretinide, thalidomide, zoledronic acid, angiostatin, apli dine, cilengtide, combret astatin A-4, endostatin • 110- 200539871 (108), halofuginone 'rebimastat, removable, Revlimid, squalamine, ukrain, and vitaminin; • Uranium coordination compounds include (but are not limited to) cis-platin, carboplatin, nedaplatin, or oxaliplatin; • Camptothecin derivatives include (but are not limited to) Camptotheca Test, 10-hydroxycamptothecin test, 9 -Aminocamptothecin, irinotecan, SN-38, edotecarin, and topotecan;

•酪胺酸激酶抑制劑是Iressa或SU5416; •抗體包含 Herceptin 、 Erbitux 、 Avast in 、或 Rituximab ; •干擾素包含干擾素〇·、干擾素a-2a、干擾素a-2b、 干擾素P、干擾素γ-la或干擾素γ-ηΐ ; •生物反應改良劑是改良有生命的有機體的防護機制 或生物反應之試劑，例如組織細胞之存活、生長或分化作 用以使組織細胞具有抗腫瘤活性。此類試劑包含krestin、 lentinan、sizofiran、picibanil、或 ubenimex ；及 •其他抗腫瘤劑包含mitoxantrone、I -天冬醯胺酶、 procarbazine、dacarbazine、羥基脲（hydroxycarbamide)、 潘司他丁（pentostatin)、或tretinoin。 本文中之“異常細胞生長”乙辭，除非特別指明，意指 與正常調節機制無關之細胞生長（例如接觸抑制功能的喪 失），包含：（1)腫瘤細胞（腫瘤）的異常生長，其係經由表 現突變的酪胺酸激酶或受體酪胺酸激酶的過度表現而增殖 ;(2)其他發生畸形酪胺酸激酶的活化之增殖性疾病之良 -111 - 200539871 (109) 性和惡性細胞的異常生長；（4)任何因受體酪胺酸激酶而 增殖的腫瘤的異常生長；（5)任何因畸形絲胺酸/蘇胺酸激 酶的活化而增殖的腫瘤的異常生長；及（6)其他發生畸形 絲胺酸/蘇胺酸激酶的活化之增殖性疾病之良性和惡性細 胞的異常生長。 本發明之化合物是有潛力之FAK蛋白質酪胺酸激酶的 抑制劑，因此適合於哺乳動物（特別是人類）之治療用途， # 作爲抗增殖劑（例如抗癌劑）、抗腫瘤劑（例如有效對抗實性 腫瘤）、抗血管形成劑（例如停止或預防血管的增殖）。特別 的是，本發明之化合物可用於預防和治療多種人類的過度 增殖的疾病，例如肝臟、腎臟、膀胱、胸部、胃、卵巢、 結腸直腸、前列腺、胰臟、肺臟、外陰、甲狀腺之惡性和 良性腫瘤、肝癌瘤、肉癌、神經膠質母細胞瘤、頭和頸之 惡性和良性腫瘤，和其他增殖的病症，例如皮膚的良性增 殖（例如牛皮癣）和前列腺的良性增殖（例如BPH)。此外， ® 預期本發明之化合物可能具有抗白血病和淋巴樣惡性腫瘤 之活性。 於本發明之一較佳體系中，癌症是選自肺癌、骨癌、 胰臟癌、胃癌、皮膚癌、頭或頸的癌症、皮膚和眼內黑色 素瘤、子宫癌、卵巢癌、婦科的癌症、直腸癌、肛門部位 的癌症、同癌、結癌、乳癌、子宫癌、輸卵管癌瘤、子 宫內膜癌瘤、子宫頸癌瘤、陰道癌瘤、外陰癌瘤、 Hodgkin氏疾病、食道癌、小腸癌、內分泌系統的癌症、 甲狀腺癌、副甲狀腺癌、腎上腺癌、軟性組織肉瘤、尿道 -112- 200539871 (110) 癌、陰莖癌、鱗狀細胞癌、前列腺癌、慢性或急性白血病 、淋巴細胞性淋巴瘤、膀胱癌、腎或輸尿管癌、腎細胞癌 瘤、腎盂癌瘤、中樞神經系統（CNS)的贅瘤、原發性CNS 淋巴瘤、脊椎腫瘤、腦癌、腦垂體腺瘤、或上述一或多種 癌症之組合。 於一較佳體系中，癌症是選自實性腫瘤，例如（但不 限於此）乳癌、肺癌 '結腸癌、腦癌、前列腺癌、胃癌、 # 胰臟癌、卵巢癌、皮膚癌（黑色素瘤）、內分泌系統的癌症 、子宫癌、睪九癌、和膀胱癌。 本發明之化合物亦可用於治療其他之涉及多種蛋白質 酪胺酸激酶相關之畸形表現配體/受體交互作用或活化作 用或訊息傳導的疾病。此類疾病可包含涉及erbB酪胺酸激 酶之畸形功能、表現、活化或訊息傳導的神經元、神經膠 質母細胞瘤、星形細胞、下丘腦、及其他腺性、巨噬細胞 、上皮、基質、和囊胚腔性質之疾病。此外，本發明之化 ® 合物可用於涉及可爲本發明之化合物所抑制之經確認和尙 未確認的酪胺酸激酶之發炎、血管形成和免疫疾病之治療 用途。 本發明之一特殊方面係有關於治療或預防哺乳動物（ 包含人類）之表現低骨質的病症之方法，其包含予需要治 療的哺乳動物投服以治療表現低骨質的病症有效量之式1 所示之化合物，或其藥學上可接受之鹽。 本發明特別有關於上述病症的治療方法，其中該表現 低骨質的病症爲骨質疏鬆、虛弱、骨質疏鬆性骨折、骨質 -113- 200539871 (111) 缺陷、兒童期特發性骨質流失、牙槽骨質流失、下頜骨質 流失、骨折、切骨術、牙周炎或義肢向內生長。 本發明之一特殊方面係有關於治療哺乳動物（包含人 類）的骨質疏鬆之方法，其包含予需要治療的哺乳動物投 服以治療骨質疏鬆有效量之式1所示之化合物，或其藥學 上可接受之鹽。 本發明之另一方面係有關治療哺乳動物（包含人類）的 • 骨折或骨質疏鬆性骨折之方法，其包含予需要治療的哺乳 動物投服以治療骨折或骨質疏鬆性骨折有效量之式1所示 之化合物，或其藥學上可接受之鹽。 “骨質疏鬆”乙辭包括原發性骨質疏鬆，例如老年骨質 疏鬆、更年期後的骨質疏鬆、和青少年期骨質疏鬆，以及 繼發性骨質疏鬆，例如甲狀腺機能亢進或Cushing氏徵候 群（因爲腎上腺皮質類固醇的使用）、肢端肥大症、生殖腺 機能不足、骨發育不全、和低磷酸鹽血症引發的骨質疏鬆 • 〇 本文中“治療（treating)”乙辭，除非特別指明，包含 逆轉、減輕、抑制該用語所應用的疾病或病症或其一或多 種的症狀之發展，或預防該疾病或病症或其一或多種的症 狀。本文中“治療（treatment)”乙辭，除非特別指明，意指 治療行爲（the act of treating)，而其中之“治療（treating)” 係如上所定義。 本發明亦提供一種藥學組成物，其包含如上所定義之 式（1)所示之化合物、或其藥學上可接受之鹽或溶劑化物 -114- 200539871 (112) ，以及藥學上可接受之助劑、稀釋劑或載體。 本發明亦提供一種製備本發明之藥學組成物的方法， 其包含混合如上所定義之式（1)所示之化合物、或其藥學 上可接受之鹽或溶劑化物，及藥學上可接受之助劑、稀釋 劑或載體。 對於上述之治療用途，投服劑量當然將根據所用的化 合物、投服模式、所欲的治療和所指明的疾病而變化。式 ® (1)所示之化合物/鹽/溶劑化合物（活性成份）的每日劑量可 爲1 mg至1 g，宜爲1 mg至250 mg，更宜是10 mg至100 mg 本發明亦涵·蓋持釋型組成物。 發明之詳細說明 式1所示之化合物可利用反應圖1所示的合成途徑而製 備。反應圖1中之取代基的定義與式1中的取代基的定義相 同。• Tyrosine kinase inhibitor is Iressa or SU5416; • the antibody contains Herceptin, Erbitux, Avast in, or Rituximab; • the interferon contains interferon 0, interferon a-2a, interferon a-2b, interferon P, Interferon gamma-la or interferon gamma-ηΐ; • Biological response modifiers are agents that improve the protective mechanisms or biological responses of living organisms, such as the survival, growth, or differentiation of tissue cells so that tissue cells have antitumor activity . Such agents include krestin, lentinan, sizofiran, picibanil, or ubenimex; and • other antineoplastic agents include mitoxantrone, I-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pentostatin, pentostatin, Or tretinoin. The term "abnormal cell growth" as used herein, unless specifically stated, means cell growth that is not related to normal regulatory mechanisms (such as loss of contact inhibition), including: (1) abnormal growth of tumor cells (tumors), which are Proliferation through overexpression of mutant tyrosine kinase or receptor tyrosine kinase; (2) other proliferative diseases of malformed tyrosine kinase activation -111-200539871 (109) Sexual and malignant cells Abnormal growth of tumors; (4) abnormal growth of any tumors proliferated by receptor tyrosine kinase; (5) abnormal growth of any tumors proliferated by activation of malformed serine / threonine kinase; and (6) ) Other benign and malignant cells with abnormal serine / threonine kinase activation in proliferative diseases. The compounds of the present invention are potential inhibitors of FAK protein tyrosine kinases, and are therefore suitable for therapeutic use in mammals (especially humans). Against solid tumors), antiangiogenic agents (such as stopping or preventing the proliferation of blood vessels). In particular, the compounds of the present invention are useful for the prevention and treatment of various human hyperproliferative diseases such as liver, kidney, bladder, chest, stomach, ovary, colorectum, prostate, pancreas, lung, vulva, malignant thyroid and Benign tumors, liver cancers, meat cancers, glioblastomas, malignant and benign tumors of the head and neck, and other proliferative disorders such as benign proliferation of the skin (such as psoriasis) and benign proliferation of the prostate (such as BPH). In addition, it is expected that the compounds of the present invention may have activity against leukemia and lymphoid malignancies. In a preferred system of the present invention, the cancer is a cancer selected from the group consisting of lung cancer, bone cancer, pancreatic cancer, gastric cancer, skin cancer, head or neck cancer, skin and eye melanoma, uterine cancer, ovarian cancer, and gynecological cancer. , Rectal cancer, anal cancer, same cancer, cancer, breast cancer, uterine cancer, fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophageal cancer, Small bowel cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethra-112- 200539871 (110) cancer, penile cancer, squamous cell carcinoma, prostate cancer, chronic or acute leukemia, lymphocytes Lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pyeloma, neoplasm of central nervous system (CNS), primary CNS lymphoma, spinal tumor, brain cancer, pituitary adenoma, or A combination of one or more of the above cancers. In a preferred system, the cancer is selected from solid tumors, such as (but not limited to) breast cancer, lung cancer, colon cancer, brain cancer, prostate cancer, gastric cancer, # pancreatic cancer, ovarian cancer, skin cancer (melanoma ), Endocrine system cancers, uterine cancers, cancers, and bladder cancers. The compounds of the present invention are also useful in the treatment of other diseases involving a variety of protein-tyrosine kinase-related malformed ligand / receptor interactions or activation or signaling. Such diseases may include neurons, glioblastomas, astrocytes, hypothalamus, and other glands, macrophages, epithelium, and stroma that are involved in the abnormal function, expression, activation, or signaling of erbB tyrosine kinase. , And diseases of the nature of the blastocyst cavity. In addition, the compounds of the present invention can be used for the treatment of inflammation, angiogenesis, and immune diseases involving confirmed and unidentified tyrosine kinases that can be inhibited by the compounds of the present invention. A special aspect of the present invention relates to a method for treating or preventing a condition exhibiting low bone mass in mammals (including humans), which comprises administering to a mammal in need of treatment an effective amount of formula 1 Or a pharmaceutically acceptable salt thereof. The present invention particularly relates to a method for treating the above-mentioned conditions, wherein the condition showing low bone mass is osteoporosis, weakness, osteoporotic fracture, bone-113-200539871 (111) defect, childhood idiopathic bone loss, alveolar bone Loss, mandibular bone loss, fractures, osteotomy, periodontitis, or prosthetic limbs grow inward. A special aspect of the present invention relates to a method for treating osteoporosis in mammals (including humans), which comprises administering to a mammal in need of treatment an effective amount of a compound of formula 1 or a pharmacological agent for treating osteoporosis Acceptable salt. Another aspect of the present invention relates to a method for treating a bone fracture or osteoporotic fracture in mammals (including humans), which comprises administering to a mammal in need of treatment an effective amount of formula 1 to treat a fracture or osteoporotic fracture. Or a pharmaceutically acceptable salt thereof. The term "osteoporosis" includes primary osteoporosis, such as osteoporosis in the elderly, post-menopausal osteoporosis, and adolescent osteoporosis, and secondary osteoporosis, such as hyperthyroidism or the Cushing's syndrome (because of the adrenal cortex Use of steroids), acromegaly, hypogonadism, bone hypoplasia, and osteoporosis caused by hypophosphatemia. 〇 “treating” in this article, unless specifically stated, includes reversal, alleviation, Inhibiting the development of a disease or disorder or one or more symptoms to which the term is applied, or preventing the disease or disorder or one or more symptoms thereof. The term "treatment" as used herein means the act of treating, unless otherwise specified, where "treating" is as defined above. The present invention also provides a pharmaceutical composition comprising the compound represented by the formula (1) as defined above, or a pharmaceutically acceptable salt or solvate thereof-114-200539871 (112), and a pharmaceutically acceptable aid Agent, diluent or carrier. The present invention also provides a method for preparing a pharmaceutical composition of the present invention, which comprises mixing a compound represented by formula (1) as defined above, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable auxiliary Agent, diluent or carrier. For the aforementioned therapeutic uses, the dosage to be administered will, of course, vary depending on the compound used, the mode of administration, the desired treatment and the disease indicated. The daily dose of the compound / salt / solvent compound (active ingredient) represented by formula (1) may be 1 mg to 1 g, preferably 1 mg to 250 mg, and more preferably 10 mg to 100 mg. · Cover release composition. DETAILED DESCRIPTION OF THE INVENTION The compound represented by Formula 1 can be prepared by using the synthetic route shown in Figure 1. The definition of the substituents in Reaction Scheme 1 is the same as the definition of the substituents in Formula 1.

反應圖1 -115- 200539871 (113) 式1所示之化合物可由5-胺基-羥吲哚（6)和嘧啶（7)作 爲起始物而製得。將7與路易士酸於惰性溶劑中在-15至45 °C之溫度下混合1〇至60分鐘，繼之加入6和適合的驗，在1 至24小時後，高產率地得到中間物4-氯嘧啶（8)。惰性溶 劑的例子包含（但不限於）THF、1,4-二噁烷、n-BuOH、i-PrOH、二氯甲烷和1,2-二氯乙烷。適合的鹼的例子包含（ 但不限於）（i)非親核性有機鹼例如三乙胺或二異丙基乙胺 # 、（Π)無機驗例如碳酸鉀或碳酸絶、或（iii)與樹脂結合的鹼 例如MP-碳酸鹽。 路易士酸的例子包含（但不限於）鎂、銅、鋅、錫或鈦 的鹵化鹽。下一個反應中，中間物8與式9所示之胺在純質 的情況下或在惰性溶劑（或溶劑混合物）的存在下在0至150 °C的溫度下反應而得到式1所示之化合物。此反應可任意 地在適合的鹼的存在下進行。適合此反應的溶劑的例子包 含（但不限於）THF、1,4-二噁烷、DM F、N-甲基-吡咯烷酮 Φ 、EtOH、n-BuOH、i -PrOH、二氯甲烷、1,2-二氯乙烷、 DMSO、或乙腈。適合的鹼係如上所述。 本發明之化合物可利用熟悉此項技術人士所習知的技 術以合成方法轉換成本發明之其他的化合物。此方法包含 (僅是用於說明方法決不用於限制）： a)利用 T.W.Greene and P.G.M.Wuts, “Protective Groups in Organic Synthesis”， Second Edition, John Wiley and Sons, New York, 1991所揭示的方法除去保護基 :例如，利用酸源（例如H Cl或三氟醋酸）除去BO C保護基 •116· 200539871 (114) b) 以官能基（例如（但不限於）一級或二級胺、硫醇、或 醇）置換離去基（鹵離子、甲磺酸根、甲苯磺酸根等）以分別 形成二級或三級胺、硫醚或醚。 c) 以一級或二級胺處理胺基甲酸苯酯（或經取代的苯 酯）以形成對應的脲（如 Thavonekham, B.et.al.Synthesis (1 997), 10, pll89所揭示者）； • d)利用氫化雙（2-甲氧乙氧基）鋁鈉（Red-A1)的處理而 將炔丙醇或高炔丙醇或N-BOC保護的一級胺還原成對應的 E-烯丙基或E-高烯丙基衍生物（如Denmark, S.E.; Jones, T.K.J.Org.Chem.(1982)47, 4595-4597 或 van Benthem, R.A.T.M.; Michels, J.J.; Speckamp, W . N . Sy n 1 e 11 (1 9 9 4), 3 6 8 - 3 7 0所揭示者）； e) 利用氫氣和Pd觸媒的處理而將炔類還原成對應的Z -燒衍生物（如 Tomassy, B.et.al.Synth.Commun.(1998), 28, • p 1 2 0 1所揭示者）； f) 一級和二級胺經異氰酸酯、醯氯（或其他活化的羧酸 衍生物）、氯甲酸烷酯/芳酯、或磺醯氯處理而形成對應的 脲、醯胺、胺基甲酸酯或磺醯胺； g) —級或二級胺與醛或酮和適合的還原劑進行還原性 胺化反應； h) 醇經異氰酸酯、醯氯（或其他活化的羧酸衍生物）、 氯甲酸烷酯/芳酯、或磺醯氯處理而形成對應的胺基甲酸 酯、酯、碳酸酯或磺酸酯。 -117- 200539871 (115) 式9所示之胺可購買得到並直接使用，或者可由熟悉 此項技術人士利用習知的化學轉換方法而製得。例如，芳 基烷基胺或雜芳基烷基胺可由對應的腈利甩例如Pd/C或 Raney鎳之觸媒進行催化性氫化反應或利用氫化鋁鋰還原 反應而製得（參見 Rylander，Catalytic Hydr〇genation in Organic Synthesis, Academic Press, 1 979) 〇Figure 1-115-200539871 (113) The compound represented by formula 1 can be prepared from 5-amino-oxindole (6) and pyrimidine (7) as starting materials. Mix 7 with Lewis acid in an inert solvent at a temperature of -15 to 45 ° C for 10 to 60 minutes, followed by adding 6 and a suitable test. After 1 to 24 hours, intermediate 4 is obtained in high yield. -Chloropyrimidine (8). Examples of inert solvents include, but are not limited to, THF, 1,4-dioxane, n-BuOH, i-PrOH, dichloromethane, and 1,2-dichloroethane. Examples of suitable bases include (but are not limited to) (i) non-nucleophilic organic bases such as triethylamine or diisopropylethylamine #, (Π) inorganic tests such as potassium carbonate or carbonate, or (iii) and Resin bound bases such as MP-carbonate. Examples of Lewis acids include, but are not limited to, halide salts of magnesium, copper, zinc, tin or titanium. In the next reaction, the intermediate 8 and the amine represented by formula 9 are reacted in the pure case or in the presence of an inert solvent (or solvent mixture) at a temperature of 0 to 150 ° C to obtain the compound represented by formula 1. Compounds. This reaction can optionally be carried out in the presence of a suitable base. Examples of solvents suitable for this reaction include, but are not limited to, THF, 1,4-dioxane, DMF, N-methyl-pyrrolidone Φ, EtOH, n-BuOH, i-PrOH, dichloromethane, 1, 2-dichloroethane, DMSO, or acetonitrile. Suitable bases are as described above. The compounds of the present invention can be synthetically converted to other compounds of the invention using techniques known to those skilled in the art. This method includes (only to illustrate that the method is not intended to limit): a) removal using the method disclosed in TWGreene and PGMWuts, "Protective Groups in Organic Synthesis", Second Edition, John Wiley and Sons, New York, 1991 Protecting group: For example, using an acid source (such as H Cl or trifluoroacetic acid) to remove the BO C protecting group • 116 · 200539871 (114) b) using functional groups (such as (but not limited to) primary or secondary amines, thiols, Or alcohol) to replace the leaving group (halide, methanesulfonate, tosylate, etc.) to form a secondary or tertiary amine, thioether or ether, respectively. c) Treatment of phenyl carbamate (or substituted phenyl ester) with a primary or secondary amine to form the corresponding urea (as disclosed by Thavonekham, B.et.al. Synthesis (1 997), 10, pll89) ; D) reduction of propargyl alcohol or homopropargyl alcohol or N-BOC-protected primary amine to the corresponding E-ene by treatment with sodium bis (2-methoxyethoxy) aluminum sodium (Red-A1); Propyl or E-high allyl derivatives (such as Denmark, SE; Jones, TKJOrg.Chem. (1982) 47, 4595-4597 or van Benthem, RATM; Michels, JJ; Speckamp, W. N. Sy n 1 e 11 (1 9 9 4), 3 6 8-3 7 0); e) reduction of alkynes to corresponding Z-burning derivatives (such as Tomassy, B by treatment with hydrogen and Pd catalyst) .et.al.Synth.Commun. (1998), 28, • disclosed in p 1 2 0 1); f) primary and secondary amines via isocyanate, ammonium chloride (or other activated carboxylic acid derivative), chlorine Alkyl formate / aryl ester, or sulfonium chloride treatment to form the corresponding urea, sulfonamide, carbamate or sulfonamide; g)-reduction of a secondary or secondary amine with an aldehyde or ketone and a suitable reducing agent Nature amination reaction; h) alcohol through isocyanate, Chloride (or other activated carboxylic acid derivative), alkyl chloroformate esters / aromatic ester, acyl chloride, or sulfonic acid to form the amine, ester, carbonate or sulfonic acid ester corresponding. -117- 200539871 (115) The amine represented by Formula 9 can be purchased and used directly, or it can be prepared by those skilled in the art using conventional chemical conversion methods. For example, arylalkylamines or heteroarylalkylamines can be prepared from the corresponding nitrile catalysts such as Pd / C or Raney nickel catalysts for catalytic hydrogenation or reduction using lithium aluminum hydride (see Rylander, Catalytic Hydr〇genation in Organic Synthesis, Academic Press, 1 979) 〇

ch3 ：n^^Nnso2ch3ch3: n ^^ Nnso2ch3

Hz/Pd/C 惰性溶劑Hz / Pd / C inert solvents

CH3 n、so2ch3 腈反應起始物可購買得到，或者根據Tschaen, D.M., et.al.Synthetic Communications( 1994), 24, 6, pp 887-890 所揭示的Pd偶合條件，由對應的芳基/雜芳基溴化物、碘 化物或三氟甲磺酸酯和Zn(CN)2製得。CH3 n, so2ch3 nitrile reaction starting materials are commercially available, or according to the Pd coupling conditions disclosed by Tschaen, DM, et.al. Synthetic Communications (1994), 24, 6, pp 887-890, the corresponding aryl / Heteroaryl bromide, iodide or triflate and Zn (CN) 2.

Zn(CN)2/ Pd 惰性溶€Zn (CN) 2 / Pd inert

so2ch3 或者，苯甲胺或雜芳基甲胺可藉由令適當的芳基烷基 或雜芳基烷基鹵化物與（BOC)2NH的鉀鹽反應（文獻）及接著 利用酸除去BOC基團而製得。so2ch3 Alternatively, benzylamine or heteroarylmethylamine can be obtained by reacting the appropriate arylalkyl or heteroarylalkyl halide with the potassium salt of (BOC) 2NH (Reference) and then removing the BOC group with an acid And made.

-118- 200539871 (116) 式9所示之胺、胺的受保護形式、胺的前驅物和胺的 受保護形式的前驅物可藉由令適當的炔或烯基錫烷、烯基 硼烷、烯基硼酸、硼酸酯與適當的芳基或雜芳基溴化物、 碘化物或三氟甲磺酸酯利用Pd偶合條件而製得（參見Tsuji, J·; Palladium Reagents and Catalysis, John Wiley and Sons 1 999及其內所引用的文獻卜-118- 200539871 (116) The amines, protected forms of amines, precursors of amines, and protected forms of amines shown in Formula 9 can be obtained by appropriate alkyne or alkenylstannane, alkenylborane , Alkenyl boronic acid, boronic acid ester, and appropriate aryl or heteroaryl bromide, iodide, or triflate are prepared using Pd coupling conditions (see Tsuji, J .; Palladium Reagents and Catalysis, John Wiley and Sons 1 999 and references cited therein

式9所示之經適當保護的胺可根據熟悉此項技術人士 所習知的方法轉換成不同之式9所示之胺，例如（但不限於 )： (a)將硫醚氧化成亞碩或碩。The appropriately protected amines shown in Formula 9 can be converted into different amines shown in Formula 9 according to methods familiar to those skilled in the art, such as (but not limited to): (a) Oxidation of thioethers to Yashuo Or master.

MCPBA惰性溶劑MCPBA inert solvent

〇2 ch3 (b)在 Brehme，R.“ Synthesis ”，（1976), PP113-114 所揭 示的相轉移的條件下令磺醯胺基苯進行N-烷基化反應。 -119- 200539871 (117)〇2 ch3 (b) N-alkylation of sulfonamidobenzene under the phase transfer conditions disclosed in Brehme, R. "Synthesis", (1976), PP113-114. -119- 200539871 (117)

、so2ch3 广丫^Br, So2ch3 Guangya ^ Br

NaOH/PTC 惰性溶劑 如熟悉此項技術人士所知，將芳基鹵化物或三氟甲磺 酸酯或雜芳基鹵化物或三氟甲磺酸酯轉換成芳族或雜芳族 胺之化學轉換反應可利用下列文獻所揭示的條件而進行： 例如，Hartwig，J.F. : “Angew.Chem.Int.Ed、”（1998),37, ρ ρ · 2 0 4 6 - 2 0 6 7 , Wolfe, J .P.; Wagaw, S .; Marcoux, J . F.; Buchwald， S . L.; aAcc.Chem.Res.,> ,(1998), 31, pp.805- 818, Wolfe, J.P·; Buchwald, S.L.; “J.Org.Chem·”，（2000), 65, pp.1144 - 1157，Muci, A . R.; Buchwald, S . L .; “Topic in Current Chemistry”（2002), pp.131-209及其引用文獻。此 外，如熟悉此項技術人士所知，上述相同的芳基或雜芳基 胺化的化學轉換反應可替代性地於腈（或一級醯胺）前驅物 # 上進行，如此在腈（或醯胺）還原反應之後得到式5所示之 胺。式5所示之經保護的胺可根據熟悉該項技術者所習知 的方法再轉換成不同之式5所示之胺。NaOH / PTC Inert Solvents Chemistry known to those skilled in the art to convert aryl halides or triflate or heteroaryl halides or triflate into aromatic or heteroaromatic amines The conversion reaction can be performed using conditions disclosed in the following literatures: For example, Hartwig, JF: "Angew.Chem.Int. Ed," (1998), 37, ρ ρ · 2 0 4 6-2 0 6 7, Wolfe, J .P .; Wagaw, S.; Marcoux, J. F .; Buchwald, S. L .; aAcc.Chem.Res., ≫, (1998), 31, pp.805- 818, Wolfe, JP · Buchwald, SL; "J.Org.Chem ·", (2000), 65, pp.1144-1157, Muci, A.R .; Buchwald, S.L .; "Topic in Current Chemistry" (2002), pp.131-209 and its references. In addition, as known to those skilled in the art, the above-mentioned chemical conversion reaction of the same aryl or heteroaryl amination can alternatively be performed on the nitrile (or primary amidine) precursor #, and thus on the nitrile (or amidine After the amine) reduction reaction, an amine represented by Formula 5 is obtained. The protected amine represented by formula 5 can be converted into a different amine represented by formula 5 according to methods known to those skilled in the art.

式1所示之化合物的活體外活性可經由下列步驟而加 以測定。更特別的是，下列分析方法提供一種測定式1所 -120- 200539871 (118) 示之化合物是否可抑制催化性構築體FAK(410_689)之酪胺 酸激酶活性的方法。此分析方法是一種以ELISA爲基礎的 形式，測量FAK(410-689)抑制poly-glu-tyr-憐酸化的能力 分析流程分爲三部份： I. His-FAK(4 1 0-68 9)之純化和裂解。 II. FAK410-689(a.k.a.FAKcd)之活化。The in vitro activity of the compound represented by Formula 1 can be measured by the following steps. More specifically, the following analytical method provides a method for determining whether the compound represented by Formula 1 -120-200539871 (118) can inhibit the tyrosine kinase activity of the catalytic construct FAK (410_689). This analytical method is an ELISA-based format that measures the ability of FAK (410-689) to inhibit poly-glu-tyr-phosphorylation. The analysis process is divided into three parts: I. His-FAK (4 1 0-68 9 ). II. Activation of FAK410-689 (a.k.a. FAKcd).

III. FAKcd激酶之 ELISA 〇 材料： -Ni-NTA瓊膠（Qiagen) -XK-16管柱（Amersham-Pharmacia) - 3 00 mM咪唑 -Superdex 200 HiLoad 16/60 製備型梯度管柱 (Amersham Biotech.) -抗體：抗磷酸酪胺酸HRP-共軛的Py20(TranSduCtionIII. ELISA for FAKcd kinase 〇 Materials:-Ni-NTA agar (Qiagen)-XK-16 column (Amersham-Pharmacia)-3 00 mM imidazole-Superdex 200 HiLoad 16/60 preparative gradient column (Amersham Biotech. )-Antibody: Anti-phosphotyrosine HRP-conjugated Py20 (TranSduCtion

-FAKcd:實驗室中純化和活化 - TMB微量盤過氧化酶基質（TMB Microwell Peroxidase-FAKcd: Purification and activation in the laboratory-TMB Microwell Peroxidase

Substrate)(Oncogene Research Product # C L 0 7) -BSA : Sigma #A3 294 -丁ween-20 ·· Sigma #P1379 - DMSO : Sigma #D-5879 一 D-PBS ·· Gibco #1 4 1 90-037 〇 121 - 200539871 (119) 純化用試劑： -緩衝液 A: 50 mM HEPES pH 7.0, 500 mM NaCl， 0.1 m Μ T C E P，Substrate) (Oncogene Research Product # CL 0 7) -BSA: Sigma # A3 294 -Ding ween-20 · Sigma # P1379-DMSO: Sigma # D-5879 -D-PBS · Gibco # 1 4 1 90-037 〇121-200539871 (119) Purification reagents:-Buffer A: 50 mM HEPES pH 7.0, 500 mM NaCl, 0.1 m TCEP,

CompleteTM蛋白酶抑制劑雞尾酒式錠劑（Roche)。 -緩衝液 B: 25 mM HEPES pH 7.0， 400 mM NaCl >CompleteTM Protease Inhibitor Cocktail Lozenges (Roche). -Buffer B: 25 mM HEPES pH 7.0, 400 mM NaCl >

0· 1 mM TCEP。 -緩衝液 C: 10 mM HEPES pH 7.5, 200 mM硫酸銨， 0· 1 mM TCEP 〇 活化用試劑： - FAK(4 10-689): 3 個冷凍管（150 μΐ/管），總共 450 μ1 ，1 · 48 mg/ml(660 pg)0 · 1 mM TCEP. -Buffer C: 10 mM HEPES pH 7.5, 200 mM ammonium sulfate, 0.1 mM TCEP 〇 Activation reagents:-FAK (4 10-689): 3 freezing tubes (150 μΐ / tube), 450 μ1 in total, 1.48 mg / ml (660 pg)

- His-Src(249-524):〜〇·74 mg/ml 母液’於 10 mM HEPES、200 mM(NH4)2S04* -Src 反應緩衝液（Upstate Biotech): 100 mM Tris-HC1 pH 7.2， 125 mM MgCl2, 25 mMMnCl2， 2 mM EDTA， 25 0 μΜ Na3V04， 2 mM DTT 〇 -122- 200539871 (120) -Μη 2 + /ATP雞尾酒式混合物（Upstate Biotech·) 7 5 m Μ Μ n C12， 500 μΜ ATP， 20 mM MOPS pH 7.2 » 1 mM Na3V04， 25 mM a-磷酸甘油酯， 5 mM EGTA，-His-Src (249-524): ~ 〇.74 mg / ml mother liquor 'in 10 mM HEPES, 200 mM (NH4) 2S04 * -Src reaction buffer (Upstate Biotech): 100 mM Tris-HC1 pH 7.2, 125 mM MgCl2, 25 mMMnCl2, 2 mM EDTA, 25 0 μM Na3V04, 2 mM DTT 〇-122- 200539871 (120)-Μη 2 + / ATP cocktail type mixture (Upstate Biotech ·) 7 5 m Μ Μ n C12, 500 μΜ ATP, 20 mM MOPS pH 7.2 »1 mM Na3V04, 25 mM a-glyceryl phosphate, 5 mM EGTA,

1 mM DTT 〇 -ATP ： 150 mM母液 - MgCl2 : 1 M母液 -DTT: 1 M母液 FAKcd激酶ELISA用試劑： -磷酸化緩衝液= 50 mM HEPES，pH 7.5， 125 mM NaCl， 4 8 m Μ M g C12 o -沖洗緩衝液：TBS + 0· 1% Tween-20 ° -阻斷緩衝液=1 mM DTT O-ATP: 150 mM mother liquor-MgCl2: 1 M mother liquor-DTT: 1 M mother liquor FAKcd kinase ELISA reagents:-Phosphorylation buffer = 50 mM HEPES, pH 7.5, 125 mM NaCl, 4 8 mM M M g C12 o-Washing buffer: TBS + 0.1% Tween-20 °-Blocking buffer =

Tris緩衝鹽水， 3% BSA ， 0.05% Tween-20，過濾過的。 -滴定盤塗覆緩衝液： 50 mg/ml 之 Poly-Glu - Tyr(Sigma #P02 7 5)，於磷酸鹽 -123- 200539871 (121) 緩衝鹽水（DPBS)中。 -ATP: 0.1 Μ 之 ATP，於1~120 或 HEPES(pH 7)中。 註：ATP分析緩衝液： 於PBS中配成75μΜ之ATP溶液，如此80 μΐ於120μ1反 應體積中的濃度=50 μΜ最終ΑΤΡ濃度。 I. His -FAKcd(410 - 689)之純化 I 1·將含有過度表現的His-FAKcd 4 1 0-689重組合蛋白 質之130 g的桿狀病毒細胞糊懸浮於3倍體積（400 ml)的緩 衝液A中， 2.使之通過菌體碎機而溶解細胞， 3·於 Sorval SLA-1 5000 轉子中在 4C 及 14000 rpm 下離 心3 5分鐘以除去細胞碎屑， 4.將上清液移至乾淨的管子中及加入6.0 ml Ni-NTA 壤膠（Q i a g e η)， b 5.懸浮液在4°C下緩緩搖動培育1小時， 6. 於旋翼式轉子中在7 00 xg下離心懸浮液， 7. 去除上清液並使瓊膠珠再懸浮於20.0 ml緩衝液A中 8.將瓊膠球移至與FPLCTM相連結之XK-16管柱 (Amersham-Pharmacia)， 9.以5倍體積的緩衝液A沖洗瓊膠珠，並以含有300 mM咪唑之緩衝液A以階梯式梯度洗提管柱， 10·對洗提出的餾份進行緩衝液交換處理使換成緩衝 -124 - 200539871 (122) 液B， 1 1 ·在交換緩衝液之後，合倂餾份及以1 : 3 00 (w/w)的 比率添加凝血酶，在13°C下培育一夜以除去N-端的His_標 (His - FAKcd 4 1 0 - 689— FAKcd 4 1 0-689(a.k.a.FAKcd))， 12·將反應混合物加回已經以緩衝液A平衡之Ni-NT A 管柱，及收集流通液， 1 3 ·濃縮流通液至1 · 7 m 1，並直接加於已經以緩衝液c • 平衡之Superdex 2 00 HiLoad 16/60製備型梯度管柱上，所 欲之蛋白質在85-95 ml洗提出， 14·將FAKcd蛋白質分成數個部份並在-80°C下冷凍乾 燥0 II. FAK之活化 1·於 450 μΐ 之 1.48 mg/ml(660 pg)FAK(410 - 689)中加入 下列：Tris buffered saline, 3% BSA, 0.05% Tween-20, filtered. -Titration plate coating buffer: 50 mg / ml of Poly-Glu-Tyr (Sigma # P02 75) in phosphate-123-200539871 (121) buffered saline (DPBS). -ATP: 0.1 mM ATP in 1 ~ 120 or HEPES (pH 7). Note: ATP analysis buffer: Prepare 75 μM ATP solution in PBS, so the concentration of 80 μΐ in 120 μ1 reaction volume = 50 μM final ATP concentration. I. Purification of His-FAKcd (410-689) I 1. Suspend 130 g of baculovirus cell paste containing over-expressed His-FAKcd 4 1 0-689 recombination protein in a 3-fold volume (400 ml) of In Buffer A, 2. Pass it through a bacterial disrupter to lyse the cells. 3. Centrifuge in a Sorval SLA-1 5000 rotor at 4C and 14000 rpm for 3 to 5 minutes to remove cell debris. 4. Discard the supernatant. Move to a clean tube and add 6.0 ml Ni-NTA clay gel (Q iage η), b 5. Suspension slowly at 4 ° C for 1 hour, 6. In a rotor rotor at 7 00 xg Centrifuge the suspension, 7. Remove the supernatant and resuspend the agar beads in 20.0 ml of buffer A 8. Move the agar balls to an XK-16 column (Amersham-Pharmacia) connected to the FPLCTM, 9. Rinse the agar beads with 5 times the volume of buffer A, and elute the column in a stepwise gradient with buffer A containing 300 mM imidazole. 10. Buffer exchange the eluted fractions to buffer- 124-200539871 (122) Solution B, 1 1 · After exchanging the buffer, combine the distillate and add thrombin at a ratio of 1: 3 00 (w / w), and incubate at 13 ° C overnight. Remove the N-terminal His_ standard (His-FAKcd 4 1 0-689-FAKcd 4 1 0-689 (akaFAKcd)), 12. Add the reaction mixture back to the Ni-NT A column that has been equilibrated with buffer A, And collect the flow-through, 1 3 · Concentrate the flow-through to 1 · 7 ml 1 and directly add it to the Superdex 2 00 HiLoad 16/60 preparative gradient column that has been equilibrated with buffer c. The desired protein is at 85 -95 ml eluted, 14. Divide the FAKcd protein into several parts and freeze-dry at -80 ° C. II. Activation of FAK 1. 1.48 mg / ml (660 pg) FAK (410-689) at 450 μΐ ) Add the following:

30 μΐ 之 0.03 7 mg/ml(l pM)His-Src(249 - 524) 30 μΐ 之 7.5 mM ATP 12 μΐ 之 20 mM MgCl2 10 μΐ 之 Mn2 + /ATP 雞尾酒式混合物（Upstate Biotech.)30 μΐ of 0.03 7 mg / ml (l pM) His-Src (249-524) 30 μΐ of 7.5 mM ATP 12 μΐ of 20 mM MgCl2 10 μΐ of Mn2 + / ATP Cocktail Mixture (Upstate Biotech.)

4 μΐ 之 6.7 mM DTT 60 μΐ 之 Src 反應緩衝液（Upstate Biotech·) 2.反應混合物在室溫下培育至少3小時 在t。時間，幾乎所有的FAKU 1 0-689)被單磷酸化，第 二個磷酸化反應是緩慢的。在t12。時間（t = 120分鐘），加 -125- 200539871 (123) 入 10 μΐ 之 150 mM ΑΤΡο T〇 =(開始）90% 單磷酸化的 FAK(4 1 0-689)(1 P04) T 4 3 =( 4 3分鐘）65%單磷酸化（1 P04)，35%二磷酸化（2 P04) T90 =(90分鐘）45% 1P04 ’ 55% 2 P04 T15〇 = 15% 1 Ρ04，85% 2 Ρ04 Τ21。= <10% 1 Ρ04，>90% 2 Ρ04，脫鹽樣品4 μΐ of 6.7 mM DTT 60 μΐ of Src reaction buffer (Upstate Biotech ·) 2. Incubate the reaction mixture at room temperature for at least 3 hours at t. Over time, almost all FAKU 1 0-689) were monophosphorylated, and the second phosphorylation reaction was slow. At t12. Time (t = 120 minutes), add -125- 200539871 (123) add 10 μΐ of 150 mM ΑΤΡο T〇 = (start) 90% monophosphorylated FAK (4 1 0-689) (1 P04) T 4 3 = (4 3 minutes) 65% monophosphorylation (1 P04), 35% diphosphorylation (2 P04) T90 = (90 minutes) 45% 1P04 '55% 2 P04 T15〇 = 15% 1 Pl04, 85% 2 Ρ04 Τ21. = < 10% 1 Ρ04, > 90% 2 Ρ04, desalted sample

3.將180 μΐ所欲之脫鹽物質加至NiNTA旋轉管柱並於 旋轉管柱上培育 4.在10k rpm下旋轉（微離心機）5分鐘以單離及收集流 通液（活化的FAK (4 1 0-6 8 9))和除去His-Sr c (滯留在管柱上）3. Add 180 μΐ of the desired desalting material to the NiNTA spin column and incubate on the spin column 4. Spin (microcentrifuge) at 10k rpm for 5 minutes to isolate and collect the flow-through (activated FAK (4 1 0-6 8 9)) and remove His-Sr c (retained on the column)

III. FAKcd激酶之 ELISA 1.以10 pg/孔的量將poly_glu-tyr(pGT)塗覆在96孔 N u n c M a X i S 〇 r p微量盤上：製備1 0 μ g / m 1之p G T的P B S溶液 ® ，分成100 μΐ/孔。在37 °c下培育微量盤一夜，吸出上清 液，以沖洗緩衝液沖洗微量盤3次，輕彈至乾燥後貯存於4 〇C下。 2. 以100% DMSO製備2.5 mM之化合物的母液。接著以 100% DMSO依序稀釋母液至60倍最終濃度，及以激酶磷酸 化緩衝液稀釋至1 : 5倍。 3. 以激酶磷酸化緩衝液製備75 μΜ之工作ATP溶液。 於每個孔中加入80 μΐ使最終ΑΤΡ濃度爲50 μΜ。 4. 於pGT分析盤之各個孔中加入10 μΐ稀釋的化合物 -126- 200539871 (124) (〇.51og連續稀釋），於同一微量盤中各個化合物重覆三次 〇 5·於冰上，以激酶磷酸化緩衝液稀釋FAKcd蛋白質至 1 : 1 000倍。於每個孔中分配30 μΐ。 6 ·註：每個批次的蛋白質之線性和適當的稀釋必須是 事先決定的。所擇之酵素濃度必須使〇D45()之分析訊號爲 約0.8-1 ·0，且在反應速率的線性範圍內。 t 7.同時製備無ATP的對照組（雜訊）和無化合物的對照 組（訊號）。 8·(雜訊）一排空白孔，含有10 μΐ之1 : 5倍稀釋的化合 物的DMSO溶液、80 μΐ磷酸化緩衝液（-ΑΤΡ)、和30 μΐ FAKcd溶液。 9·(訊號）對照孔，含有1〇 μΐ之由1 ·· 5倍稀釋之 DMSO(-化合物）於激酶磷酸化緩衝液中所形成的溶液、80 μΐ 之 75 μΜ ATP、及 30 μΐ 之 1 ·· 1000 FAKcd 酶。 > 10.反應混合物於微量盤振盪器上在室溫下緩緩振盪 培育15分鐘。 11·藉由吸取反應混合物及以沖洗緩衝液沖洗3次以中 止反應。 12·以阻斷緩衝液稀釋磷酸-酪胺酸HRP-共軛 (PY2 0HRP)抗體至0.250 pg/ml(母液之1 : 1〇〇〇倍稀釋）。於 每孔中分配1〇〇 μΐ，及在室溫下振盪培育30分鐘。 13·吸取上清液及以沖洗緩衝液沖洗3次。 14.於每孔中加入100 μΐ室溫的ΤΜΒ溶液以產生色彩。 -127- 200539871 (125) 在約15-30秒後藉由於各孔中添加100 μ!之〇·〇9 M H2S04 以中止色彩的產生。 15·於BioRad微量盤讀取器或可讀取〇D45Q之微量盤讀 取器上測量在450 nm的吸收以定量訊號。 16.抑制酪胺酸激酶活性將導致吸收訊號的降低。訊 號通常是0.8-1.0 OD單位。所得的數據係以IC5()s(pM)表示III. ELISA for FAKcd kinase 1. Coat poly_glu-tyr (pGT) at a rate of 10 pg / well on a 96-well N unc M a X i S 〇rp microplate: prepare 10 μ g / m 1 p GT in PBS solution, divided into 100 μΐ / well. Incubate the microplate overnight at 37 ° C, aspirate the supernatant, rinse the microplate 3 times with washing buffer, flick until dry, and store at 40 ° C. 2. Prepare a stock solution of 2.5 mM compounds in 100% DMSO. The mother liquor was then sequentially diluted to 100-fold final concentration with 100% DMSO, and diluted to 1: 5-fold with kinase phosphorylation buffer. 3. Prepare 75 μM working ATP solution with kinase phosphorylation buffer. Add 80 μΐ to each well so that the final ATP concentration is 50 μM. 4. Add 10 μΐ of diluted compound-126-200539871 (124) (0.51 og serial dilution) to each well of pGT analysis plate, and repeat each compound three times in the same micro dish. Phosphorylation buffer dilutes FAKcd protein to 1: 1000 times. Dispense 30 μΐ into each well. 6 · Note: The linearity and proper dilution of the protein in each batch must be determined in advance. The chosen enzyme concentration must be such that the analytical signal of OD45 () is approximately 0.8-1 · 0 and within a linear range of the reaction rate. t 7. Simultaneously prepare a control group (noise) without ATP and a control group (signal) without compound. 8. · (Noise) A row of blank wells containing 10 μΐ of a DMSO solution diluted 1: 5 times, 80 μΐ of phosphorylation buffer (-ATP), and 30 μΐ of FAKcd solution. 9. (Signal) Control well, containing 10 μΐ of a solution of DMSO (-compound) diluted 1 ·· 5 times in kinase phosphorylation buffer, 80 μΐ of 75 μM ATP, and 30 μΐ of 1 · 1000 FAKcd enzyme. > 10. The reaction mixture was incubated on a microplate shaker at room temperature with gentle shaking for 15 minutes. 11. Stop the reaction by aspirating the reaction mixture and rinsing 3 times with washing buffer. 12. Dilute the phospho-tyrosine HRP-conjugate (PY2 0HRP) antibody to 0.250 pg / ml in blocking buffer (1: 1000 dilution of mother liquor). Dispense 100 μΐ into each well and incubate with shaking for 30 minutes at room temperature. 13. Aspirate the supernatant and rinse 3 times with washing buffer. 14. Add 100 μΐ room temperature TMB solution to each well to produce color. -127- 200539871 (125) After about 15-30 seconds, the generation of color was stopped by adding 100 μ! Of 0.99 M H2S04 to each well. 15. Quantify the signal by measuring the absorption at 450 nm on a BioRad microdisk reader or a microdisk reader capable of reading OD45Q. 16. Inhibition of tyrosine kinase activity will result in a decrease in the absorption signal. The signal is usually 0.8-1.0 OD units. The obtained data is expressed as IC5 () s (pM)

以FAK可誘導的細胞爲基礎的ELISA :最終流程 材料=FAK-Inducible Cell-Based ELISA: Final ProcessMaterials =

Reacti - Bind Goat Anti - Rabbit Plates 96 - well(Pierce -Product#15135ZZ @115.00 USD) FAKpY397兔子多株抗體（Biosource #44624 @315.00 USD)Reacti-Bind Goat Anti-Rabbit Plates 96-well (Pierce -Product # 15135ZZ @ 115.00 USD) FAKpY397 rabbit polyclonal antibody (Biosource # 44624 @ 315.00 USD)

Chr omePure Rabbit I gG * 整個分子（Jackson Laboratories #00 1-000-003 @60/25mg USD) UBI aFAK 選殖的 2A7 鼠單株抗體（Upstate#05- 182 @289.00 USD) 過氧化酶"共軛的 AffiniPur e Goat Anti-Mouse I g G ( Jackson Lab #115-035-146 @95/1.5 ml USD)Chr omePure Rabbit I gG * Entire molecule (Jackson Laboratories # 00 1-000-003 @ 60 / 25mg USD) UBI aFAK-selected 2A7 mouse monoclonal antibody (Upstate # 05- 182 @ 289.00 USD) peroxidase " total AffiniPur e Goat Anti-Mouse I g G (Jackson Lab # 115-035-146 @ 95 / 1.5 ml USD)

SuperBlock TBS(Pierce Pr o d u c t # 3 7 5 3 5 Z Z @99 USD) 牛血清白蛋白（Sigma #A - 9647 @117.95/100 g USD) TMB 過氧化酶受質（Oncogene Research Products #CL07-100 ml @40.00 USD) -128 - 200539871 (126)SuperBlock TBS (Pierce Pr oduct # 3 7 5 3 5 ZZ @ 99 USD) Bovine serum albumin (Sigma #A-9647 @ 117.95 / 100 g USD) TMB peroxidase substrate (Oncogene Research Products # CL07-100 ml @ (40.00 USD) -128-200539871 (126)

Na3VO^ 釩酸鈉（Sigma #S6 50 8 @43.9 5 /5 0 g USD) MTT 受質（Sigma #M_2128 @2 5.95/500 mg USD) 生長介質：DMEM + 10%FBS，P/S，Glu，750 pg/ml Zeocin 和 50 pg/ml 濕黴素（Zeocin In Vitro gen #R25〇-〇5 @ 725 USD和濕黴素 InVitrogen #R2 20-05 @150 USD)Na3VO ^ Sodium vanadate (Sigma # S6 50 8 @ 43.9 5/5 0 g USD) MTT substrate (Sigma # M_2128 @ 2 5.95 / 500 mg USD) Growth medium: DMEM + 10% FBS, P / S, Glu, 750 pg / ml Zeocin and 50 pg / ml Wetomycin (Zeocin In Vitro gen # R25〇-〇5 @ 725 USD and Wetomycin InVitrogen # R2 20-05 @ 150 USD)

Mifepristone InVitrogen #H110_01 @125 USDMifepristone InVitrogen # H110_01 @ 125 USD

CompleteTM# EDTA的蛋白酶抑制劑球粒Boehringer Mannheim #1873580 用以選擇激酶依賴性的phosph〇FAKY397之以FAK細 胞爲基礎的分析流程 步驟： 發展以可誘導的FAK細胞爲基礎之ELISA形式的分析 以篩選出用以鑑定酪胺酸激酶專一性抑制劑之化學物質。 以細胞爲基礎的分析利用GeneSwitchTM系統（inVitrogen)的 機制以外源性地控制FAK和在基團Y397之激酶依賴性自磷 酸化位點之表現和磷酸化反應。 抑制Y397之激酶依賴性自磷酸化反應導致OD45。之吸 收訊號的降低。訊號通常是0.9-1. 5 OD45。單位，雜訊的範 圍係0.08-0.1 OD45。單位。所得的數據係以IC5()s(hM)表示 〇 第1天，於T175燒瓶內培養A431 _FAKwb在進行以 FAK細胞爲基礎的分析之前的當天，於96孔U型底微量盤 上，將A43rFAKwt細胞植入生長介質中。在誘導FAK之前 -129- 200539871 (127) ，使細胞在37°C和5% C02下置放6至8小時。以100%乙醇製 備10 μΜ之Mifepristone母液。於生長介質中依序將母液稀 釋至l〇x最終濃度。將10 μΐ此稀釋液移至各個孔中（最終濃 度 0.1 nM Mifepristone)。使細胞在 37t：和 5% C02 下置放 一夜（12至16小時）。同時亦製備無Mifepristone誘導之FAK 表現和磷酸化反應之對照孔。CompleteTM # EDTA Protease Inhibitor Pellet Boehringer Mannheim # 1873580 FAK cell-based analysis procedure for selecting kinase-dependent phosphOFAKY397 Steps: Develop an assay based on inducible FAK cells for screening Chemicals used to identify specific inhibitors of tyrosine kinase. Cell-based analysis utilizes the mechanism of the GeneSwitchTM system (inVitrogen) to control exogenously the expression and phosphorylation response of FAK and the kinase-dependent autophosphorylation site at group Y397. Inhibition of the kinase-dependent autophosphorylation reaction of Y397 leads to OD45. The absorption signal decreases. The signal is usually 0.9-1. 5 OD45. Unit, the range of noise is 0.08-0.1 OD45. unit. The data obtained are expressed as IC5 () s (hM). On the first day, A431_FAKwb was cultured in a T175 flask. The day before FAK cell-based analysis was performed on a 96-well U-shaped microplate, A43rFAKwt Cells are implanted in growth media. Prior to induction of FAK -129- 200539871 (127), cells were allowed to stand at 37 ° C and 5% C02 for 6 to 8 hours. A 10 μM Mifepristone stock solution was prepared with 100% ethanol. The mother liquor was sequentially diluted to a final concentration of 10x in the growth medium. Transfer 10 μΐ of this dilution to each well (final concentration of 0.1 nM Mifepristone). Allow the cells to stand overnight at 37t: and 5% C02 (12 to 16 hours). Control wells without Mifepristone-induced FAK performance and phosphorylation were also prepared.

第 2 天，在 Goat Anti-Rabbit PI at e s 上塗覆以 3 · 5 ® pg/ml之磷酸專一性的FAKpY397多株抗體（於SuperBlock TBS緩衝液中），並使之在微量盤振盪器上在室溫下振盪微 量盤2小時。任意地，對照孔上可塗覆以3.5 με/ιη1之對照 的捕捉（Capture)抗體（整個兔子的IgG分子）（於SuperBlock TBS中）。使用緩衝液沖洗掉過量的FAKpY397抗體三次。 將200 μΐ/孔的3%BSA/0.5% Tween阻斷緩衝液加至塗覆有 Anti-FAKpY3 97的微量盤中並在微量盤振盪器上在室溫下 振盪1小時以進行阻斷作用。進行阻斷作用期間，以100% ^ DMSO製備5 mM之化合物母液。接著以100% DMSO將母液 依序稀釋至lOOx最終濃度。將ΙΟΟχ溶液於生長介質中稀釋 成1: 10稀釋液，並於各個含有經FAK誘導或無誘導之對 照的A431細胞的孔中置入10 μΐ適當的化合物稀釋液，在 3 7t和5% C02下歷時30分鐘。製備RIPA溶胞緩衝液（50 mM Tris-HU，pH 7·4、1% NP-40、0.25%脫氧膽酸鈉⑽-deoxycholate)、 15 0 mM NaC1、 1 mM EDTA、1 mMOn day 2, Goat Anti-Rabbit PI at es was coated with 3 · 5 ® pg / ml phosphate-specific FAKpY397 polyclonal antibody (in SuperBlock TBS buffer) and placed on a microplate shaker. The microplate was shaken at room temperature for 2 hours. Optionally, the control wells can be coated with a 3.5 με / ιη1 control capture antibody (the entire rabbit IgG molecule) (in SuperBlock TBS). Rinse off excess FAKpY397 antibody three times with buffer. 200 μΐ / well of 3% BSA / 0.5% Tween blocking buffer was added to a microplate coated with Anti-FAKpY3 97 and shaken on a microplate shaker at room temperature for 1 hour to effect blocking. During the blocking effect, a 5 mM stock solution of the compound was prepared with 100% ^ DMSO. The mother liquor was then sequentially diluted to 100x final concentration with 100% DMSO. The 100 × solution was diluted to 1:10 dilution in growth medium, and 10 μΐ of the appropriate compound dilution was placed in each well containing FAK-induced or non-induced control A431 cells at 37 T and 5% C02. It lasted 30 minutes. Preparation of RIPA lysis buffer (50 mM Tris-HU, pH 7.4, 1% NP-40, 0.25% sodium deoxycholate-deoxycholate), 150 mM NaC1, 1 mM EDTA, 1 mM

Na3V04、1 mM N a F 和每 5 0 ml 溶液一粒 C o m p 1 e t e TM 無 E D 丁 A 的蛋白酶抑制劑球粒）。30分鐘之化合物處理後，以TBS- -130- 200539871 (128) 丁沖洗緩衝液沖洗掉化合物三次。以100 μ】/ml RI PA緩衝 液溶解細胞。 去除被塗覆的微量盤上之阻斷緩衝液，並以TBS-T沖 洗緩衝液沖洗三次。利用96-孔微量盤自動微量分配器， 將100 μΐ全細胞溶解產物（得自第6步驟）置於塗覆有Goat Anti - Rabbit FAKpY39 7的微量盤上以捕捉 ph〇sph〇FAKY397蛋白質。在室溫下振盪2小時。以TBS-T ® 沖洗緩衝液沖洗掉未結合的蛋白質三次。製備0.5 pg/ml(l :2000倍稀釋）之 UBI otFAK檢測抗體於 3%BSA/0.5% Tween 阻斷緩衝液之溶液。於每孔中分配100 μΐ UB I aF A K溶液 ，並在室溫下振盪30分鐘。以TBS-T沖洗緩衝液沖洗掉過 量的UBI aFAK抗體三次。製備0·8 pg/ml(l : 5000倍稀釋） 之二級Anti-Mouse過氧化酶（Anti-2MHRP)共轭抗體。於每 孔中分配1〇〇 μΐ Anti-2MHRP溶液，並在室溫下振盪30分 鐘。以TBS-T沖洗緩衝液沖洗掉過量的Anti-2MHRP抗體三 ^ 次。在室溫下於各孔中加入1〇〇 μΐ TMB受質溶液使產生色 彩。於各孔中加入1〇〇 μΐ ΤΜΒ中止溶液（0.09 M H2S04)以 中止TMB反應，並於Bio Rad微量盤讀取器上測量在450 nm 的吸收以定量訊號。 其他的FAK細胞分析法亦可參考Pfizer代理人文件編 號 PC 1 1 699，標題爲 “INDUCIBLE FOCAL ADHESION KINASE CELL ASSAY”。 於一較佳體系中，根據激酶分析，例如本文中所述者 ，本發明之化合物具有低於50 0 ηΜ之活體外活性。較佳的 -131 - 200539871 (129) 是，本發明之化合物於激酶分析中之IC5。低於25 ηΜ，更 宜低於10 ηΜ。另一較佳體系中，本發明之化合物於FAK 細胞基礎的分析，例如本文中所述者，展現出IC5。低於1 μΜ，更宜是低於100 ηΜ，最宜是低於25 ηΜ。 此外，下列分析可用於分析本發明之化合物之如上所 述之抑制骨質疏鬆及/或低骨質的能力。 • (1)待測化合物對於老年之未損傷的或摘除卵巢的雌鼠之 體重、身體組成和骨密度的影響 此分析可用於測試待測化合物對於老年之未損傷的或 摘除卵巢的（OVX)雌鼠模式的影響。 硏究流程 18個月大的Sprague-Dawley雌鼠經過假裝（sham)或 OVX的手術，同時有一組老鼠在第0天經過驗屍以作爲基 ® 礎線控制組。於手術後的第1天，開始以載體或待測化合 物處理老鼠。載體或待測化合物是利用皮下注射（s.c.)的 方式每週投服二次（星期二和星期五），待測化合物係以每 天每公斤體重10 mg(10 mg/kg/day)的平均劑量投服。 所有的鼠均於檢驗屍體前第2和12天經皮下注射以1〇 mg/kg calcein(Sigma，St.Louis, MO)作爲螢光骨豁標記。 在檢驗屍體的當天，所有經ketamine/xylazine麻醉的老鼠 均經稱重及利用配備有鼠全身掃瞄軟體之雙能量X-光骨密 度測量儀（DXA, QDR-45 00/W, Hologic Inc·，Waltham, -132- 200539871 (130) ΜA)進行瘦和肥骨質的測定。檢驗屍體，接著解剖屍體及 利用心臟穿刺取得血液。利用末端定量的X射線電腦斷層 攝影法（PQCT)分析各隻鼠的末端股骨幹骺端和股骨幹， 及測量總體積的、小梁骨的和皮質骨的礦物質含量和骨密 度。 末端定量的X射線電腦斷層攝影法（pQCT):使用具 5.4〇版軟體之？<3(：丁\-射線儀器（54&4(：\0：丁1^56&1^}11^, N 〇 rl an d M e d i c al Sy s t e m , F 〇 rt At k in s ο n , WI)掃猫股骨切 片。自離末端約5.0 mm (近端股骨幹骺端，主要的海綿狀 骨位置）和13 mm(股骨幹，皮質骨位置）之股骨幹骺端取出 厚度1 mm的橫切片，體積方塊大小爲0.10 mm。使用輪廓 模式2和皮質模式4以定義及分析皮質骨。設定外臨界値爲 340 mg/crn3以區分皮質殻與軟組織，並設定內臨界値爲 5 29 mg/cm3以區分沿著內皮質表面之皮質骨。小梁骨的測 量係在使用剝除模式4且設定臨界値爲65 5 mg/cni3以區分 • 皮質（下）骨骼和海綿狀骨骼的條件下進行。同時亦利用額 外的同心剝除法（定義的海綿狀骨骼之1%)以確定消除所有 分析中的皮質（下）骨骼。測量小粱骨和皮質骨之體積含量 、密度和區域（Jamsa T.et al., Bone 23: 1 55- 1 66, 1998; K e , H.Z.et al. , Journal of Bone and Mineral Research、16 :765-773,2001)。 陰道組織學：將陰道組織固著及埋入石蠟中。切出5 μιη切片並以Alcian Blue染色劑染色。對陰道內腔上皮厚 度和黏多醣（分泌的細胞）進行組織學檢查。 -133- 200539871 (131) 分析的實驗組係如下： 第I組：基礎控制組 第II組：Sham +載體 第III組：OVX +載體 第IV組：OVX +待測化合物（l〇/mg/kg/天，於載體 中） • (2)骨折癒合分析 (a)在全身投服後對骨折癒合之影響的分析 骨折技術：3個月大的Sprague-Dawley老鼠經 ketamine麻醉。在右脛骨或股骨的近端的前內側造成1 cm 切口。以下說明脛骨手術技術。切口是一直到骨骼，在距 離脛骨粗隆末端4 mm及距前脊內側2 mm處鑽出1 mm的洞 。利用0_ 8 mm不銹鋼管（在與骨骼相同的條件下測試出最 大負載量36.3 N，最大硬度61.8 N/mm)在骨髓腔內插釘。 ® 不挖出骨髓管。使用特殊設計之具有鈍鉗口的可調式鉗子 利用三點彎曲法在脛腓連結點上方2 mm處形成標準的閉 合性骨折。爲了使軟骨的傷害減少至最低，小心照顧以不 使骨折移位。利用單絲尼龍縫線縫合皮膚。所有的操作是 在無菌的狀態下進行。在插釘後立即取得所有骨折的放射 線圖，且排除骨折在特定的骨幹區域外或釘子移位的老鼠 。其餘的動物隨意地分成下列群組，在每個測試骨折癒合 的時間點每組均有10至12隻動物。第1組每天強飼1 ml/鼠 之載體（水：100%乙醇=95 : 5)，而其他組則每日強飼0.01 •134- 200539871 (132) 至100 mg/kg/天之待測化合物（1 ml/鼠）達10、20、40和80 在10、20、40和80天時，使各組之10-12隻老鼠經 ketamine麻醉，並使之失血死亡。利用解剖法取出脛腓骨 並剝除軟組織。各組之5-6隻老鼠的骨骼貯存於70%乙醇中 以供組織分析，而各組之另外5-6隻老鼠則貯存於經緩衝 的Ringer氏溶液（+ 4 °C，pH 7.4)中以供測量放射線圖和進 ®行生物力學試驗。 組織分析：骨折的組織分析方法已經爲Mosekilde和 Bak 戶斤幸艮導（The Effects of Growth Hormone on Fracure Healing in Rats : A Histological D e s c r i p t i ο n . B ο n e , 1 4 · 19 -27,1 993)。簡言之，鋸開骨折點8 mm至骨折線的二側， 在不除去骨骼的鈣質的情況下將骨骼埋於甲基丙烯酸甲酯 中，於Reichert-Jung Polycut切片機上將額骨切成厚8 μπι 的切片。Masson-Trichrome染色的額中部切片（包含脛骨 ® 和腓骨）用於視覺化反應有或無治療的骨折癒合的細胞和 組織。將經天狠星紅染色的切片用於證明癒合組織結構的 特性及區分骨折點之網狀骨骼和片狀骨骼。進行以下的測 量：（1)骨折裂口 -測量骨折中皮質骨端點間的最短距離， (2)癒合組織的長度和直徑，（3)癒合組織的總骨體積區域 ，（4)癒合組織區域內之每個組織的似骨組織，（5)癒合組 織中的纖維組織，及（6)癒合組織中的軟骨區域。 生物力學分析：生物力學分析的方法已經爲Bak和 Andressen 所報導（The Effects of Aging on Fracture -135- 200539871 (133)Na3V04, 1 mM Na F, and one Cop p 1 e t e TM protease inhibitor pellet without E D but A per 50 ml of solution). After 30 minutes of compound treatment, the compound was washed three times with TBS-130-200539871 (128) butane rinse buffer. Cells were lysed with 100 μ】 / ml RI PA buffer. Remove blocking buffer from the coated microplate and rinse three times with TBS-T wash buffer. Using a 96-well microplate automatic microdistributor, 100 μΐ of whole cell lysate (obtained from step 6) was placed on a microplate coated with Goat Anti-Rabbit FAKpY39 7 to capture the phosphOFAKY397 protein. Shake at room temperature for 2 hours. Rinse unbound protein three times with TBS-T ® wash buffer. Prepare a solution of 0.5 pg / ml (l: 2000-fold dilution) of UBI otFAK detection antibody in 3% BSA / 0.5% Tween blocking buffer. Dispense 100 μΐ of UB I aF A K solution into each well and shake at room temperature for 30 minutes. Rinse off excess UBI aFAK antibody three times with TBS-T wash buffer. A secondary Anti-Mouse peroxidase (Anti-2MHRP) conjugate antibody was prepared at 0.8 pg / ml (1: 5000-fold dilution). Dispense 100 μΐ of Anti-2MHRP solution into each well, and shake at room temperature for 30 minutes. The excess Anti-2MHRP antibody was washed out three times with TBS-T washing buffer. 100 μΐ TMB substrate solution was added to each well at room temperature to produce color. Add 100 μΐ TMB stop solution (0.09 M H2S04) to each well to stop the TMB reaction, and measure the absorption at 450 nm on a Bio Rad microplate reader to quantify the signal. Other FAK cell analysis methods can also refer to Pfizer agent document number PC 1 1 699, entitled "INDUCIBLE FOCAL ADHESION KINASE CELL ASSAY". In a preferred system, the compounds of the invention have an in vitro activity of less than 50 nM based on kinase analysis, such as those described herein. Preferred -131-200539871 (129) is the IC5 of a compound of the present invention in a kinase assay. Below 25 ηM, more preferably below 10 ηM. In another preferred system, FAK cell-based analysis of compounds of the invention, such as those described herein, exhibits IC5. Below 1 μM, more preferably below 100 ηM, and most preferably below 25 ηM. In addition, the following analysis can be used to analyze the ability of the compounds of the present invention to inhibit osteoporosis and / or low bone mass as described above. • (1) Effect of test compound on body weight, body composition, and bone density of aged, uninjured or ovarian-extracted female rats. This analysis can be used to test the test compound for undamaged or ovarian-extracted (OVX) in the elderly. Effects of female rat patterns. Study process An 18-month-old female Sprague-Dawley rat underwent sham or OVX surgery, while a group of mice underwent autopsy on day 0 as the baseline control group. On the first day after surgery, mice were started to be treated with the carrier or the test compound. The vehicle or test compound is administered subcutaneously (sc) twice a week (Tuesday and Friday). The test compound is administered at an average dose of 10 mg (10 mg / kg / day) per kilogram of body weight per day. . All rats were subcutaneously injected with 10 mg / kg calcein (Sigma, St. Louis, MO) as fluorescent markers on the 2nd and 12th days before the cadaver examination. On the day of the corpse examination, all rats anesthetized with ketamine / xylazine were weighed and used a dual-energy X-ray bone density meter (DXA, QDR-45 00 / W, Hologic Inc. , Waltham, -132- 200539871 (130) MA) for lean and fatty bone. Examine the cadaver, then dissect the corpse and obtain blood by cardiac puncture. X-ray computed tomography (PQCT) was used to analyze the distal femoral metaphysis and femoral shaft of each mouse, and the mineral content and bone density of total volume, trabecular bone, and cortical bone were measured. X-ray computed tomography (pQCT) for terminal quantification: using software with version 5.40? < 3 (: 丁 \ -Ray Instrument (54 & 4 (: \ 0: 丁 1 ^ 56 & 1 ^) 11 ^, N 〇rl an d M edic al Sy stem, F 〇rt At k in s ο n , WI) Scan the femoral section of the cat. Take a 1 mm thick femoral metaphysis from the distal femoral metaphysis, which is the proximal femoral metaphysis, the main spongy bone location, and 13 mm (femoral shaft, cortical bone location). Transverse section with a volume square size of 0.10 mm. Use contour mode 2 and cortical mode 4 to define and analyze cortical bone. Set the outer critical mass to 340 mg / crn3 to distinguish the cortical shell from soft tissue, and the inner critical mass to 5 29 mg / cm3 to distinguish cortical bone along the surface of the inner cortex. Trabecular bone was measured using a stripping mode 4 with a critical threshold of 65 5 mg / cni3 to distinguish between • cortical (lower) bone and spongy bone Performed. Additional concentric stripping (1% of the defined spongy bones) was also used to determine the elimination of cortical (lower) bones in all analyses. Measurement of trabecular and cortical bone volume content, density, and area (Jamsa T .et al., Bone 23: 1 55- 1 66, 1998; K e, HZet al., Journal of Bone and Mine ral Research, 16: 765-773, 2001). Vaginal histology: fixation and embedding of vaginal tissue in paraffin. 5 μm sections were cut out and stained with Alcian Blue stain. Vaginal lumen epithelial thickness and mucopolysaccharides ( (Secreted cells) for histological examination. -133- 200539871 (131) The experimental groups analyzed were as follows: Group I: Basic Control Group II: Sham + Vector Group III: OVX + Vector Group IV: OVX + Test compound (10 / mg / kg / day in vehicle) • (2) Fracture healing analysis (a) Analysis of the effect on fracture healing after systemic administration Fracture technique: 3 months old Sprague-Dawley Mice were anesthetized with ketamine. A 1 cm incision was made in the right tibia or the proximal anterolateral aspect of the femur. The tibial surgical technique is described below. The incision is made all the way to the bone, 4 mm from the end of the tibial tuberosity and 2 mm from the medial side of the anterior spine A 1 mm hole is made. A 0-8 mm stainless steel tube (tested with a maximum load of 36.3 N and a maximum hardness of 61.8 N / mm under the same conditions as bone) is used to insert the nail in the bone marrow cavity. ® Do not excavate the bone marrow tube. Use Specially designed adjustable pliers with blunt jaws By three-point bending at 2 mm above the tibiofibular junction point formed at a standard closed fracture. For cartilage damage reduced to a minimum, in order to take good care not to displace the fracture. The skin was sutured with monofilament nylon sutures. All operations are performed under sterile conditions. Radiographs of all fractures were obtained immediately after the insertion, and rats with fractures outside the specific backbone area or nail displacement were excluded. The remaining animals were randomly divided into the following groups, with 10 to 12 animals in each group at each time point at which fracture healing was tested. Group 1 gavaged 1 ml / rat of vehicle (water: 100% ethanol = 95: 5) daily, while other groups gavaged 0.01 • 134- 200539871 (132) to 100 mg / kg / day to be tested Compounds (1 ml / mouse) for 10, 20, 40, and 80 At 10, 20, 40, and 80 days, 10-12 mice in each group were anesthetized with ketamine, and blood was lost to death. Anatomically remove the tibia and fibula and remove the soft tissue. The bones of 5-6 mice in each group were stored in 70% ethanol for tissue analysis, while the other 5-6 mice in each group were stored in buffered Ringer's solution (+ 4 ° C, pH 7.4) For measuring radiographs and conducting biomechanical tests. Tissue analysis: The method of tissue analysis of fractures has been provided by The Effects of Growth Hormone on Fracure Healing in Rats: A Histological D escripti ο n. B ο ne, 1 4 · 19 -27, 1 993 ). In brief, saw the fracture point 8 mm to both sides of the fracture line, bury the bone in methyl methacrylate without removing the calcium of the bone, and cut the frontal bone on a Reichert-Jung Polycut microtome Into 8 μm thick slices. Masson-Trichrome stained midfrontal sections (including tibia ® and fibula) are used to visualize the healing of fractured cells and tissues with or without treatment. Sections stained with celestial red were used to prove the characteristics of the healing tissue structure and distinguish the reticular and sheet bones of the fracture site. The following measurements were performed: (1) Fracture fracture-measure the shortest distance between the cortical bone endpoints in the fracture, (2) the length and diameter of the healing tissue, (3) the total bone volume area of the healing tissue, (4) the healing tissue area Bone-like tissue within each tissue, (5) fibrous tissue in the healing tissue, and (6) cartilage area in the healing tissue. Biomechanical analysis: The method of biomechanical analysis has been reported by Bak and Andressen (The Effects of Aging on Fracture -135- 200539871 (133)

Healing i n Rat s · C a 1 c i f · Ti s s u e I n t · 4 5 : 2 9 2 - 2 9 7 , 1 98 9) 0 簡言之，所有骨折的放射線圖係在生物力學試驗之前測量 。癒合中的骨折之力學性質係利用破壞性三或四點彎曲法 分析的。測量最大負載量、硬度、最大負載時之能量、最 大負載時之撓度、和最大應力。 (b)在局部投服後對骨折癒合之影響的分析 B 骨折技術：硏究中使用麻醉狀態下之2歲大的雌或雄 性小獵犬。利用 Lenehan 等人（Lenehan, T.M.; Balligand， Μ. ; Nunamaker, D.M.; Wood, F.E. ： Effects of EHDP on Fracture Healing in Dogs.J.Orthop.Res.3 : 499 - 507; 1 98 5)所揭示之三點彎曲法緩慢且連續地增加負載而形成 橫向放射狀骨折。將線拉過骨折點以確定完成解剖學地瓦 解骨骼。接著，利用緩釋型藥九或化合物之適合的調合物 (例如膏、膠、溶液或懸浮液）緩緩地釋出化合物的方式將 t 前列腺素激動劑局部地輸送至骨折點，歷時10、15或20週 〇 組織分析：骨折的組織分析方法已經爲Peter等人 (Peter, C.P.; Cook, W.O.; Nunamaker, D.M.; Provost, M.T.; Seedor, J.G.; Rodan, G.A.Effects of alendronate on fracture healing and bone remodeling in dogs.J. Orthop.Res.14 : 74-70, 1996)及 Mosekilde 和 Bak(丁heHealing i n Rat s · C a 1 c i f · Ti s s u e In t · 4 5: 2 9 2-2 9 7, 1 98 9) 0 In short, the radiographs of all fractures were measured before the biomechanical test. The mechanical properties of the healing fracture were analyzed using the destructive three- or four-point bending method. Measure maximum load, hardness, energy at maximum load, deflection at maximum load, and maximum stress. (b) Analysis of the effect on fracture healing after local administration. B Fracture technique: A 2-year-old female or male beagle under anesthesia was used in the study. Lenehan et al. (Lenehan, TM; Balligand, M .; Nunamaker, DM; Wood, FE: Effects of EHDP on Fracture Healing in Dogs. J. Orthop. Res. 3: 499-507; 1 98 5) The three-point bending method slowly and continuously increases the load to form a transverse radial fracture. Pull the thread through the fracture point to confirm complete dissection of the bone. Next, the t-prostaglandin agonist is locally delivered to the fracture site by slowly releasing the compound using a suitable release compound (such as a paste, gum, solution, or suspension) of the sustained-release drug nine or compound, which lasts 10, 15 or 20 weeks. Tissue analysis: The method of fracture tissue analysis has been Peter and others (Peter, CP; Cook, WO; Nunamaker, DM; Provost, MT; Seedor, JG; Rodan, GAEffects of alendronate on fracture healing and bone remodeling in dogs.J. Orthop.Res. 14: 74-70, 1996) and Mosekilde and Bak (丁 he

Effects of Growth Hormone on Fracure Healing in Rats ： A Histological Description.Bone, 14 ·· 19-27，1993)所報 -136- 200539871 (134) 導。簡言之，在殺死動物後，鋸開骨折點3 mm至骨折線 的二側，在不除去骨骼的鈣質的情況下將骨骼埋於甲基丙 嫌酸甲酯中，於R e i c h e r t - J u n g Ρ ο 1 y c u t切片機上將額骨切 成厚8 μπι的切片。Masson-Trichrome染色的額中部切片（ 包含脛骨和腓骨）用於視覺化反應有或無治療的骨折癒合 的細胞和組織。將經天狠星紅染色的切片用於證明癒合組 織結構的特性及區分骨折點之網狀骨骼和片狀骨骼。進行 ® 以下的測量：（1)骨折裂口-測量骨折中皮質骨端點間的最 短距離，（2)癒合組織的長度和直徑，（3)癒合組織的總骨 體積區域，（4)癒合組織區域內之每個組織的似骨組織， (5)癒合組織中的纖維組織，及（6)癒合組織中的軟骨區域 〇 生物力學分析：生物力學分析的方法已經爲Bak和 Andressen(The Effects of Aging on Fracture Healing in Rats.Calcif.Tissue Int.45 ： 29 2-29 7，1 9 8 9)及 P e t e r 等人 • (Peter, C.P·; Cook, W.O.; Nunamaker, D.M·; Provost, M . T . ; Seedor，J . G . ; R o d an , G.A.Effects of Alendronate On Fracture Healing And Bone Remodeling In D ogs. J. Orthop. Res. 1 4 : 74-7 0, 1 996)所報導。簡言之，所有骨折 的放射線圖係在生物力學試驗之前測量。癒合中的骨折之 力學性質係利用破壞性三或四點彎曲法分析的。測量最大 負載量、硬度、最大負載時之能量、最大負載時之撓度、 和最大應力。 本發明之化合物（以下稱爲“活性化合物”）的投服可利 -137 - 200539871 (135) 用任何可將化合物輸送至作用位置之方法。這些方法包含 口服途徑、十二指腸內投服途徑、非經腸注射（包含靜脈 內、皮下、肌內、血管內或灌注）投服、局部投服、和直 腸投服。 活性化合物之投服量決定於待治療患者、疾病或病症 的嚴重性、投服的頻率、化合物的性質、和診斷的醫師的 判斷。然而，有效劑量的範圍係每天每公斤體重約0.001 至約100 mg，宜約1至約35 mg/kg/天，單劑或多重劑。對 7〇公斤的人類而言，其量係約0.05至約7 g/天，宜約0.2至 約2.5 g/天。在某些情況中，低於上述範圍之下限的劑量 可能是更爲適合的，然而在其他的情況，仍可使用較高的 劑量而不會造成任何有害的副作用，其先決條件是此較高 劑量是先分成數個小劑量而於一天內分次投服。 活性化合物可以單一治療劑的形式使用，或可與一或 多種其他的抗腫瘤物質倂用，該其他的抗腫瘤物質的例子 是選自，例如，有絲分裂抑制劑（例如vinblastine);院化 劑（例如順銷（cis-platin)、卡銷（carboplatin)和環碟醯胺 (cyclophosphamide));抗代謝劑（例如5-氟尿嘧啶、阿拉伯 糖胞苷和羥基脲，或，例如，歐洲專利案239362所揭示之 較佳的抗代謝劑之一，例如N-(5-[N-(3,4_二氫-2-甲基-4-酮咱唑啉-6-基甲基）-N-甲胺基卜2_噻吩甲醯基）-L-穀 胺酸）；生長因子抑制劑；細胞週期抑制劑；嵌入性抗生 素（例如阿黴素Udriamycin)和博萊黴素（bleomycin));酵素 (例如干擾素）；和抗荷爾蒙劑（例如抗雌激素劑，例如， -138- 200539871 (136) Ν ο 1 v a d e χ τ M (t a m o x i f e η)或，例如，抗雄激素劑，例如 0&3〇(^1^(4’-氰基-3-(4-氟苯磺醯基）-2-羥基-2-甲基-3 ’-（三氟甲基）丙醯替苯胺））。此種聯合治療可利用同時、 先後或分別投服各別治療用的成份之方法而達成。 藥學組成物可呈，例如，適合口服的型式（例如錠劑 、膠囊、九劑、粉末、持釋型調合物、溶液、懸浮液）、 適合非經腸注射的型式（例如無菌溶液、懸浮液或乳液）、 ^ 局部投服的型式（例如軟膏或乳霜）、或經直腸投服的型式（ 例如栓劑）。藥學組成物可呈適合單次投服正確劑量之單 劑型式。藥學組成物將包含習用的藥學載體或賦形劑，以 及作爲活性化合物之本發明的化合物。此外，藥學組成物 亦可包含其他的藥用的或藥學的試劑、載體、助劑等。 非經腸投服的劑型的例子包含活性化合物於無菌水溶 液（例如水性丙二醇或葡萄糖溶液）中所形成的溶液或懸浮 液。此種劑型必要時可適當地添加緩衝液。 ® 適合的藥學載體包含惰性稀釋劑或塡充劑、水和各種 有機溶劑。必要時，藥學組成物可含有其他成份，例如調 味劑、結合劑、賦形劑等。因此，爲了經口投服的目的， 可使用含有下列成份之錠劑：各種賦形劑（例如檸檬酸）以 及各種崩散劑（例如澱粉、藻酸和一些複合型矽酸鹽）與結 合劑（例如蔗糖、明膠和金合歡膠）。此外，爲了製錠的目 的通常可使用潤滑劑，例如硬脂酸鎂、月桂醯硫酸鈉和滑 石。亦可使用類似型態的固體組成物作爲軟和硬質明膠膠 囊的塡充物，此類物質較宜包含乳糖或奶糖和高分子量聚 -139- 200539871 (137) 乙二醇。當使用水性懸浮液或酏劑經口投服時，其中之活 性化合物可與多種增甜劑或調味劑、色料或染料、及必要 時乳化劑或懸浮劑以及稀釋劑（例如水、乙醇、丙二醇、 甘油或其混合物）一起倂用。 具有特定量之活性化合物之各種藥學組成物的製法是 爲熟悉此項技術人士所習知或明白者，例如，參見 Remington’s Pharmaceutical Sciences, Mack Publishing Company, Easter, Pa . , 15th E d i t i ο n ( 1 9 7 5 )。 下列實例和製法將進一步說明和例示本發明之化合物 及其製法。須明白的是，本發明之範圍絕不受限於下列實 例和製法。下列實例中之具有單一對掌中心的分子，除非 特別指明，係以外消旋混合物的形式存在。而具有二或多 個對掌中心的分子，除非特別指明，係以非鏡像異構物之 外消旋混合物的形式存在。單一鏡像異構物/非鏡像異構 物可利用熟悉此項技術人士所習知的方法獲得。 當下列製備例和實例中使用HPLC層析時，除非特別 指明，所用的條件係如下所述。所用的管柱是長1 50 mm 和內徑 4.6 mm之 Z〇RBAXTM RX C 1 8 管柱（H e wl e 11 Packard 製 造）。樣品係利用Hewlett Packard-1100系統分析。使用的 梯度溶劑法是10 0%醋酸銨/醋酸緩衝液（〇·2 M)至10 0%乙腈 ，歷時1〇分鐘。接著系統進行沖洗循環，包含1〇〇%乙腈沖 洗1.5分鐘及接著100%緩衝液沖洗3分鐘。期間內的流速固 定爲3 mL/分鐘。 -140- 200539871 (138) 【實施方式】 實施例 一般方法 5-硝基-羥吲哚之製備： 在-15°C的溫度下，於由羥吲哚（26 g)於100 mL濃硫 酸所形成的溶液中逐滴加入發煙硝酸（8.4 mL)。小心地維 持反應溫度在-1 5 °C。加完後，攪拌反應3 0分鐘，接著倒 入水中。形成黃色沉澱物，過濾以分離出沉澱物，得34 g(98%)5-硝基-羥吲哚。 5-胺基-羥吲哚（2)之製備： 於Parr瓶中在由5-硝基-羥吲哚（25 g)於120 mL二甲基 乙醯胺所形成的溶液中加入10% Pd/C (0.5 g)。混合物經氫 化（40 psi H2)16小時。過濾除去觸媒，濾液經乙醚（2 L)稀 釋得5-胺基-羥吲哚（10.5 g，50%)。 2,4-二氯-5-三氟甲基嘧啶（3)之製備： 5 -三氟甲基尿嘧啶（250 g，1.39 mmol)和三氯氧化磷 (655 mL’ 6·94 mmol)置於配備有架空式攪拌器、回流冷 凝管、加液漏斗和內熱電偶之3 L的4-頸燒瓶內。在維持 內容物處於氮氣氛中的情況下於淤漿內一次加入濃磷酸 (8 5wt% ’ 9·5 mL，0·1當量），此時溫和地放熱。接著在使 完成添加時之反應混合物的內部溫度達到8 5-9 0 °C的速率 下，逐滴加入二異丙基乙胺（245 mL，1.39 mmol，1當量） -141 - 200539871 (139) ，歷時1 5分鐘。當加完胺後，反應混合物係呈均勻的淡橘 色溶液。開始加熱，維持橘色溶液在100 °C達20小時，此 時反應混合物之HPLC分析顯示反應起始物消牦完。除去 外部加熱，將燒瓶的內容物冷卻至40 °C，接著逐滴加至冰 冷之由3 N HC1(5 L，10當量）和乙醚（2 L)所形成的混合物 中，使反應驟停瓶的溫度保持在10至15 °C間。分層，水層 經醚（1 L)萃取一次。合倂的有機層經水沖洗至洗液呈中 性（1.5 L沖洗5次），以MgS 0 4乾燥，及濃縮至得288 g(產 率95%)淡黃-橙色油狀物，純度96%(HPLC)。此物質可利用 蒸餾（在79 mmHg下bp 109°C)而進一步純化。 5-（4_氯-5-三氟甲基-嘧啶-2-基胺基）-1,3-二氫-吲哚-2-酮（2)之製備：Effects of Growth Hormone on Fracure Healing in Rats: A Histological Description. Bone, 14 · 19-27, 1993) -136- 200539871 (134). In brief, after killing the animal, saw the fracture point 3 mm to both sides of the fracture line, and bury the bone in methyl methylpropionate without removing the calcium of the bone. In Reichert- Cut the frontal bone into 8 μm thick slices on a ycut slicer. Masson-Trichrome stained midfrontal sections (including tibia and fibula) are used to visualize the healing of fractured cells and tissues with or without treatment. Sections stained with celestial red were used to prove the characteristics of the healing tissue structure and distinguish the reticular and sheet bones of the fracture site. Take the following measurements: (1) Fracture fracture-measure the shortest distance between the end points of the cortical bone in the fracture, (2) the length and diameter of the healing tissue, (3) the total bone volume area of the healing tissue, (4) the healing tissue Bone-like tissue of each tissue in the area, (5) fibrous tissue in the healing tissue, and (6) cartilage area in the healing tissue. Biomechanical analysis: The method of biomechanical analysis has been Bak and Andressen (The Effects of Aging on Fracture Healing in Rats.Calcif.Tissue Int. 45: 29 2-29 7, 1 9 8 9) and Peter et al. (Peter, CP ·; Cook, WO; Nunamaker, DM ·; Provost, M. T .; Seedor, J. G .; Rod an, GAEffects of Alendronate On Fracture Healing And Bone Remodeling In Dogs. J. Orthop. Res. 1 4: 74-7 0, 1 996). In short, the radiographs of all fractures were measured before the biomechanical test. The mechanical properties of the healing fractures were analyzed using the destructive three- or four-point bending method. Measure maximum load, hardness, energy at maximum load, deflection at maximum load, and maximum stress. Administration of the compound of the present invention (hereinafter referred to as "active compound") can be carried out by any method capable of delivering the compound to the action site. These methods include oral administration, intraduodenal administration, parenteral (including intravenous, subcutaneous, intramuscular, intravascular, or perfusion) administration, topical administration, and rectal administration. The amount of active compound administered depends on the severity of the patient, disease or condition to be treated, the frequency of administration, the nature of the compound, and the judgment of the physician who diagnoses it. However, the effective dose ranges from about 0.001 to about 100 mg per kg of body weight per day, preferably about 1 to about 35 mg / kg / day, single or multiple doses. For a human of 70 kg, the amount is about 0.05 to about 7 g / day, preferably about 0.2 to about 2.5 g / day. In some cases, doses below the lower limit of the above range may be more suitable, but in other cases, higher doses can still be used without causing any harmful side effects, a prerequisite is that this is higher The dose is divided into several small doses and administered several times a day. The active compound may be used in the form of a single therapeutic agent or may be used in combination with one or more other antitumor substances, examples of which are selected from, for example, mitotic inhibitors (such as vinblastine); For example, cis-platin, carboplatin, and cyclophosphamide); anti-metabolites (such as 5-fluorouracil, arabinosine, and hydroxyurea), or, for example, European Patent No. 239362 One of the better anti-metabolites disclosed, such as N- (5- [N- (3,4-dihydro-2-methyl-4-ketoxazoline-6-ylmethyl) -N-formyl Aminyl 2-thienylmethyl) -L-glutamine); Growth factor inhibitors; Cell cycle inhibitors; Embedded antibiotics (such as doxorubicin Udriamycin and bleomycin)); Enzymes (such as Interferon); and antihormonal agents (such as anti-estrogen agents, such as -138- 200539871 (136) Ν ο 1 vade χ τ M (tamoxife η), or, for example, anti-androgen agents, such as 0 & 3〇 ( ^ 1 ^ (4'-cyano-3- (4-fluorobenzenesulfonyl) -2-hydroxy-2-methyl-3 '-(trifluoromethyl) propanil )). This combination therapy can be achieved by simultaneous, sequential or separate administration of the individual therapeutic ingredients. The pharmaceutical composition can be, for example, a form suitable for oral administration (eg tablets, capsules, nine doses, powders) , Sustained release formulations, solutions, suspensions), types suitable for parenteral injection (such as sterile solutions, suspensions or emulsions), ^ topical administration (such as ointments or creams), or rectal administration (E.g. suppositories). The pharmaceutical composition can be in a single dosage form suitable for a single dose. The pharmaceutical composition will contain conventional pharmaceutical carriers or excipients and the compounds of the invention as active compounds. In addition, The pharmaceutical composition may also include other medicinal or pharmaceutical agents, carriers, adjuvants, etc. Examples of parenteral dosage forms include solutions of the active compound in a sterile aqueous solution (such as an aqueous propylene glycol or glucose solution) Or suspension. This dosage form can be appropriately buffered if necessary. ® Suitable pharmaceutical carriers include inert diluents or elixirs, water and An organic solvent. If necessary, the pharmaceutical composition may contain other ingredients, such as flavoring agents, binding agents, excipients, etc. Therefore, for the purpose of oral administration, tablets containing the following ingredients can be used: various excipients (Such as citric acid) and various disintegrating agents (such as starch, alginic acid, and some composite silicates) and binding agents (such as sucrose, gelatin, and acacia). In addition, lubricants are often used for the purpose of tabletting, Examples include magnesium stearate, sodium lauryl sulfate, and talc. Solid compositions of a similar type can also be used as fillings in soft and hard gelatin capsules. Such materials preferably include lactose or milk sugar and high molecular weight poly-139 -200539871 (137) Glycol. When an aqueous suspension or tincture is administered orally, the active compound therein can be combined with a variety of sweetening or flavoring agents, colors or dyes, and if necessary, emulsifying or suspending agents and diluents (such as water, ethanol, Propylene glycol, glycerin or mixtures thereof). Various pharmaceutical compositions with specific amounts of active compounds are prepared by those skilled in the art or understand, for example, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easter, Pa., 15th E diti ο n (1 9 7 5). The following examples and preparation methods will further illustrate and exemplify the compounds of the present invention and their preparation methods. It should be understood that the scope of the present invention is by no means limited to the following examples and manufacturing methods. Molecules with a single palm center in the following examples exist as racemic mixtures unless otherwise specified. Molecules with two or more palm centers, unless otherwise specified, exist as racemic mixtures of non-mirromeric isomers. Single enantiomers / non-enantiomers can be obtained by methods known to those skilled in the art. When HPLC chromatography is used in the following Preparations and Examples, the conditions used are as described below unless otherwise specified. The column used was a ZORBAXTM RX C 1 8 column (made by Hewl e 11 Packard) with a length of 150 mm and an inner diameter of 4.6 mm. The samples were analyzed using a Hewlett Packard-1100 system. The gradient solvent method used was 100% ammonium acetate / acetic acid buffer (0.2 M) to 100% acetonitrile for 10 minutes. The system was then flushed with 100% acetonitrile for 1.5 minutes and then 100% buffer for 3 minutes. The flow rate during the period was fixed at 3 mL / min. -140- 200539871 (138) [Embodiment] Example General method Preparation of 5-nitro-oxindole: At a temperature of -15 ° C, a solution of oxindole (26 g) in 100 mL of concentrated sulfuric acid was prepared. To the resulting solution was added dropwise fuming nitric acid (8.4 mL). Carefully maintain the reaction temperature at -15 ° C. After the addition was complete, the reaction was stirred for 30 minutes and then poured into water. A yellow precipitate formed and was filtered to isolate the precipitate to give 34 g (98%) of 5-nitro-oxindole. Preparation of 5-amino-oxindole (2): In a Parr bottle, add 10% Pd to a solution of 5-nitro-oxindole (25 g) in 120 mL of dimethylacetamide. / C (0.5 g). The mixture was hydrogenated (40 psi H2) for 16 hours. The catalyst was removed by filtration, and the filtrate was diluted with ether (2 L) to give 5-amino-oxindole (10.5 g, 50%). Preparation of 2,4-dichloro-5-trifluoromethylpyrimidine (3): 5-trifluoromethyluracil (250 g, 1.39 mmol) and phosphorus trichloride (655 mL '6.94 mmol) In a 3-L 4-neck flask equipped with an overhead stirrer, reflux condenser, addition funnel, and internal thermocouple. While maintaining the contents in a nitrogen atmosphere, concentrated phosphoric acid (85% by weight '9.5 mL, 0.1 equivalent) was added to the slurry in one portion, at which time it exothermed gently. Then, diisopropylethylamine (245 mL, 1.39 mmol, 1 equivalent) was added dropwise at a rate such that the internal temperature of the reaction mixture at the completion of the addition reached 8 5-9 0 ° C -141-200539871 (139) It took 15 minutes. When the amine was added, the reaction mixture was a homogeneous light orange solution. Heating was started and the orange solution was maintained at 100 ° C for 20 hours. At this time, HPLC analysis of the reaction mixture showed that the reaction starting material had been consumed. After removing the external heating, the contents of the flask were cooled to 40 ° C, and then added dropwise to an ice-cold mixture of 3 N HC1 (5 L, 10 equivalents) and diethyl ether (2 L), and the reaction was quenched. Keep the temperature between 10 and 15 ° C. The layers were separated and the aqueous layer was extracted once with ether (1 L). The combined organic layer was washed with water until the washing solution became neutral (5 times with 1.5 L), dried over MgS 0 4 and concentrated to give 288 g (yield 95%) of a pale yellow-orange oil with a purity of 96. % (HPLC). This material can be further purified by distillation (bp 109 ° C at 79 mmHg). Preparation of 5- (4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole-2-one (2):

在由5-三氟甲基-2,4-二氯嘧啶（214.8 g，0.921 mmol)於1 : 1 DCE/tBuOH(1.240 L)所形成的溶液中加入1 Μ之氯化鋅的乙醚溶液（1當量，0.921 L)。0.5小時後，加 入5-胺基-羥吲哚（124 g，0.837 mmol)，繼之加入三乙胺 (129.4 mL，0·921 mmol)，且保持溫度在25°C ^在室溫下 攪拌反應混合物一夜，接著濃縮，並以甲醇碾製產物得黃 色固體（224.3 g，82%)。 】H - NMR(DMS〇-d6，400MHz) ： <5 3.29(s，2H)，6.76(d , J = 7.9Hz，2H)，7.39(d，J = 8.3Hz)，7.51(br s ， 1H)， 8.71(s，1H)，10.33(s，1H)，10.49(s，lH)〇 13C NMR(DMS〇-d6 ， 100MHz) ： δ 177.0 ， 161.3 ， -142- 200539871 (140) 158.7(br)，140.7，132.8，126.9，123.7(q，J = 268Hz)， 121.0，118.7，111.2(q，J = 32Hz)，109.6，36.7 ； HPLC 遲 滯時間：5.759分鐘。LRMS(M + )329.1，331.1。 實例1 5-[4-(1^-1-苯基-乙胺基）-5_三氟甲基-嘧啶-2-基胺基]-To a solution of 5-trifluoromethyl-2,4-dichloropyrimidine (214.8 g, 0.921 mmol) in 1: 1 DCE / tBuOH (1.240 L) was added a 1 M solution of zinc chloride in ether ( 1 equivalent, 0.921 L). After 0.5 hours, add 5-amino-oxindole (124 g, 0.837 mmol), followed by triethylamine (129.4 mL, 0.921 mmol), and keep the temperature at 25 ° C. Stir at room temperature The reaction mixture was overnight, then concentrated, and the product was triturated with methanol to give a yellow solid (224.3 g, 82%). H-NMR (DMS 0-d6, 400 MHz): < 5 3.29 (s, 2H), 6.76 (d, J = 7.9 Hz, 2H), 7.39 (d, J = 8.3 Hz), 7.51 (br s, 1H), 8.71 (s, 1H), 10.33 (s, 1H), 10.49 (s, 1H) 〇13C NMR (DMS〇-d6, 100MHz): δ 177.0, 161.3, -142- 200539871 (140) 158.7 (br ), 140.7, 132.8, 126.9, 123.7 (q, J = 268Hz), 121.0, 118.7, 111.2 (q, J = 32Hz), 109.6, 36.7; HPLC hysteresis time: 5.759 minutes. LRMS (M +) 329.1, 331.1. Example 1 5- [4- (1 ^ -1-phenyl-ethylamino) -5_trifluoromethyl-pyrimidin-2-ylamino]-

在 1 : 1 DCE/t - BuOH(l ·· 1比率，4 mL)和 5-（4-氯一 5 -三氟甲基-嘧啶-2-基胺基）-1,3-二氫-吲哚-2-酮（〇· 15 g， 0.456 mmol)之溶液中加入（R)( + )-cx-苯乙胺（0· 071 mL， 0·54 7 mmol)和二異丙基乙胺（0.081 mL，0.456 mmol)。所 得之溶液在氮氣下攪拌並加熱至80°C歷時16小時。將反應 混合物冷卻至室溫，以〜10 mL之二氯甲烷和甲醇之1 : 1混 合物稀釋，繼之加入0.5 g MP-碳酸鹽。所得之混合物經 攪拌、過濾、濃縮及矽膠層析純化（97 : 2.8 : 0· 3氯仿/甲 醇/濃氫氧化銨），得所欲之標題化合物，爲白色固體 (0.021 g ， 11%) 。 HPLC 遲滯時間：6·46 分鐘。 LRMS(M + )413.4。 下列本發明之化合物係根據實例1之方法藉由加熱氯 •143- 200539871 (141) 嘧啶（4)與適當的胺而製得。此反應中所用的胺可由市面 購得或者利用熟悉此項技術人士所習知之胺的一般合成方 法製得。除非特別指明，帶有對掌中心的化合物得到的是 外消旋混合物形式。At 1: 1 DCE / t-BuOH (1 ·· 1 ratio, 4 mL) and 5- (4-chloro-5 -trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro- To a solution of indole-2-one (0.15 g, 0.456 mmol) was added (R) (+)-cx-phenylethylamine (0.071 mL, 0.547 mmol) and diisopropylethylamine (0.081 mL, 0.456 mmol). The resulting solution was stirred under nitrogen and heated to 80 ° C for 16 hours. The reaction mixture was cooled to room temperature, diluted with ~ 10 mL of a 1: 1 mixture of dichloromethane and methanol, followed by the addition of 0.5 g of MP-carbonate. The resulting mixture was purified by stirring, filtration, concentration, and silica gel chromatography (97: 2.8: 0.3 chloroform / methanol / concentrated ammonium hydroxide) to obtain the desired title compound as a white solid (0.021 g, 11%). HPLC latency: 6.46 minutes. LRMS (M +) 413.4. The following compounds of the present invention were prepared according to the method of Example 1 by heating chlorine 143-200539871 (141) pyrimidine (4) and an appropriate amine. The amine used in this reaction may be commercially available or prepared by a general synthetic method of amines familiar to those skilled in the art. Unless otherwise specified, compounds with the center of the palm are obtained as a racemic mixture.

表1·根據實例1之方法所製得的化合物 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N -（1-甲基-1-苯基-乙基）-3-{[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜| 苯磺醯胺 6.46 597.5 3-{[2-(2 -酮- 2,3 -二氫-1H -吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺 基]-甲基卜苯磺醯胺 4.87 479.1 5 - {4-[3-(三氟甲磺醯基）-苯甲胺基 ]-5-二氣甲基-嘧11定-2-基胺基}-1，3-二氫-吲哚-2-酮 6.35 532.1 5-{4-[(哌啶-3-基甲基）-胺基]-5-三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮 3.74 407.3 -144- 200539871 (142) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[(1-甲擴醯基-呢Π定-3-基甲基 )-胺基]-5 -三氟甲基-喃卩定-2-基胺基 }-1，3-二氫-吲哚-2-酮 5.21 485.2 1^-(3-{[2-（2-酮-2,3-二氫-川-卩引11朵-5 -基胺基）-5-三氟^甲基-嘧卩定-4-基 胺基]-甲基卜苯基）_甲磺醯胺 5.22 493.3 3- 酮-3-(3-{[2-(2_酮-2,3-二氫-11^-吲哚-5-基胺基）-5-三氟甲基-嘧啶- 4- 基胺基]-甲基}_呢陡-1-基）_丙腈 4.92 474.3 5-{4-[3-(1,1-二酮-1N6-異噻唑烷-2-基）_丙胺基]-5-三氟甲基-嘧陡-2-基胺基卜1，3-二氫- η引π朵-2-酮 4.89 471.1 5 - [4-(2-甲基-丁胺基）-5-三氟甲基-嘧啶_2-基胺基]-1，3-二氫-吲哚-2-酮 6.53 380.3 5 - {4-[(1-甲磺醯基-1派淀-2-基甲基 )-胺基]-5 -三氟甲基-嘧Π定-2-基胺基 }-1,3-二氫-吲哚-2-酮 5.17 485.3 N-{2_[2_(2 -嗣- 2,3 -二氯弓丨 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基 胺基]-乙基卜甲磺醯胺 4.38 431.2 •145- 200539871 (143) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) -{4-[2-(2-酮-2,3 二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺 基]-丁基}_甲磺醯胺 4.78 459.3 - {4-[(1_甲磺醯-呢陡-4-基甲基）-基 ]_5 -三氣甲基-嘧Π定-2-基胺基}-1,3-二氫-吲哚-2-酮 5.22 485.3 N-甲基-N-{2-[2-（2-酮-2,3-二氫-1H -卩引卩朵一5-基胺基）一5 -三氟甲基-嘧 啶-4-基胺基]-甲基卜乙基）-甲磺醯 胺 4.81 445.1 甲磺酸 3-{[2-(2-酮- 2,3-二氫-1H-吲 卩朵-5 -基胺基）-5-三氟甲基-嚼卩定-4-基胺基]_甲基卜苯酯 5.67 494.1 N-{3-[2-(2-酮-2,3-二氫-1H-吲哚-5 -基胺基）-5 -三氟甲基-喃B定-4 -基 胺基]-丙基}-甲磺醯胺 4.58 445.1 5 - {4-[(4 -甲磺醯基-嗎啉-2-基甲基 )-胺基]-5-三氣甲基-II·密D定-2-基胺基 卜1,3-二氫-吲哚-2-酮 4.87 48 7.2 -146 - 200539871 (144) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 1^-(4-氣-3-{[2-（2-嗣-2,3-二氯-114-卩引D朵-5 -基胺基）-5_三氟甲基-喃卩定-4-基胺基]-甲基}-苯基）-甲磺醯胺 5.29 511.1 5 - {4-[(5 -酮-嗎啉-2 -基甲基）-胺基 ]-5_三氟甲基-嘧陡-2-基胺基卜1,3-二氫-吲哚-2-酮 4.12 423.3 ]\1-（4-甲氧基-3_{[2-(2-嗣-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺 5.38 5 2 3.2 N -（4-甲基-3-{[2-(2-嗣-2,3-二氮-1H -卩引D朵-5 -基胺基）-5-三氟甲基一嘧 啶-4_基胺基]-甲基卜苯基）-甲磺醯 胺 5.30 5 07.2 5 - [4_ (3-甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧卩定-2-基胺基]-1,3-二 氫-吲哚-2-酮 5.14 492.2 5-{4_ [(4-三氟乙醯基-嗎啉-2-基甲 基）-胺基卜5 -三氟甲基-喃陡-2-基胺 基}-1，3-二氫-吲11朵-2-酮 5.64 5 05.1 -147- 200539871 (145) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-{4-[(1-甲磺醯基-氮雜環丁烷-3 -基甲基）_胺基]-5-三氟甲基-嘧啶-2-基胺基}-1,3 -二氫-D引D朵-2 -酮 4.76 45 7.2 N-甲基 - N-（4- 甲基 -3-{[2_(2-嗣-2,3 -二氫-1H -卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基 )-甲磺醯胺 6.66 521.3 5-{4-[(1_甲磺醯基-吡咯烷-3_基甲 基）-胺基]-5 -三氟甲基-嘧陡-2-基胺 基}-1,3 -二氫-巧丨D朵-2-酮 4.97 471.2 1^-甲基-1^1-{3-[2-（2-嗣-2,3-二氯-1H - D引卩朵一 5-基胺基）一5 -三氟甲基-嘧 啶-4-基胺基]-丙基卜甲磺醯胺 5.02 459.2 5 - {4-[2-(1_甲磺酿基-呢Π定-2-基甲 基）-乙胺基]_5_三氟甲基-嘧啶-2-基 胺基卜1，3 -二氫-D引η朵-2-酮 5.71 499.4 5 - {4-[(4_甲磺醢基-D比陡-2-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1,3-二氫-吲哚_2-酮 4.68 4 79.1 -148 - 200539871 (146) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) {2,2 -二甲基- 3- [2-(2 -酮-2,3-二氫-1H-卩弓|卩朵一5-基胺基）-5 -三氟甲基一喃 啶-4-基胺基]-丙基}-胺基甲酸第三 丁酯 7.01 495.0 5 - [4-(3-異丙氧基-丙胺基）-5-三氟 甲基-嘧啶-2-基胺基]-1,3-二氫-吲 哚-2_酮 6.27 410.4 5- {4 - [(1-甲基-呢陡-3-基甲基）-胺 基]-5-三氟甲基-嘧啶-2-基胺基}-1 , 3 -二氫-D引Π朵-2 -酮 3.71 421.0 5-{4-[(四氫吡喃-4-基甲基）-胺基]-5-三氟甲基-嘧啶_2_基胺基}-1,3-二 氫-吲哚-2-酮 5.16 408.3 5 - [4-(2 -乙基-丁胺基）-5 -三氟甲基-嘧啶-2-基胺基]-1,3-二氫-吲哚_2-酮 6.95 3 94.3 5- {4-[(四氫呋喃-2 R-基甲基）-胺基 ]-5 -三氟甲基-嘧卩定-2-基胺基卜1,3-二氫-吲哚-2-酮 5.30 394.3 -149- 200539871Table 1 Compounds prepared according to the method of Example 1 Compound name HPLC Hysteresis time (minutes) MS data (M + H) N-(1-methyl-1-phenyl-ethyl) -3-{[2 -(2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbutane | benzenesulfonamide 6.46 597.5 3-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbull Benzsulfenylamine 4.87 479.1 5-{4- [3- (trifluoromethanesulfonyl) -benzylamino] -5-difluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indole-2-one 6.35 532.1 5- {4-[(piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1, 3-Dihydro-indole-2-one 3.74 407.3 -144- 200539871 (142) Compound name HPLC Hysteresis time (minutes) MS data (M + H) 5-{4-[(1-methylexpanyl-? Π 定 -3-ylmethyl) -amino] -5 -trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-indole-2-one 5.21 485.2 1 ^- (3-{[2- (2-Keto-2,3-dihydro-Chrysene-Hydroxyl 11-5-ylamino) -5-trifluoro ^ methyl-pyrimidine-4-ylamino ] -Methylbuthylphenyl) _methanesulfonamide 5.22 493.3 3-keto-3- (3- {[2- (2_keto-2,3-dihydro-11 ^ -indole-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} _ Steep-1-yl) _propionitrile 4.92 474.3 5- {4- [3- (1,1-dione-1N6-isothiazolidin-2-yl) _propylamino] -5-trifluoromethyl-pyrimidine Dino-2-ylaminopyridine 1,3-dihydro-η-π-do-2-one 4.89 471.1 5-[4- (2-methyl-butylamino) -5-trifluoromethyl-pyrimidine_ 2-ylamino] -1,3-dihydro-indole-2-one 6.53 380.3 5-{4-[(1-methylsulfonyl-1pyridin-2-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 5.17 485.3 N- {2_ [2_ (2-嗣-2,3 -di Chloride 丨 D-5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -Ethylmethylsulfonamide 4.38 431.2 • 145- 200539871 (143) Compound name HPLC hysteresis time (Min) MS data (M + H)-{4- [2- (2-keto-2,3 dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Methylamino] -butyl} -methanesulfonylamine 4.78 459.3-{4-[(1_Methanesulfonyl-methane-4-ylmethyl) -yl] _5-trifluoromethyl-pyrimidine 2-ylamino} -1,3-dihydro-indole-2-one 5.22 485.3 N-methyl-N- {2- [2- (2-one-2,3-dihydro-1H-卩 引 卩 朵Mono-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuethyl) -methanesulfonylamine 4.81 445.1 methanesulfonic acid 3-{[2- (2-one-2 , 3-dihydro-1H-indiodo-5 -ylamino) -5-trifluoromethyl-methylpyridin-4-ylamino] -methylphenylphenyl ester 5.67 494.1 N- {3- [ 2- (2-keto-2,3-dihydro-1H-indole-5 -ylamino) -5 -trifluoromethyl-pyranidine-4 -ylamino] -propyl} -methanesulfonate Hydrazine 4.58 445.1 5-{4-[(4-methylsulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-II · did-2-ylamino Bu 1,3-dihydro-indole-2-one 4.87 48 7.2 -146-200539871 (144) Compound name HPLC hysteresis time (minutes) MS data (M + H) 1 ^-(4- 气 -3- { [2- (2-fluorene-2,3-dichloro-114-pyridine-5-ylamino) -5_trifluoromethyl-pyridin-4-ylamino] -methyl} -Phenyl) -methanesulfonamide 5.29 511.1 5-{4-[(5-keto-morpholine-2 -ylmethyl) -amino] -5_trifluoromethyl-pyrimidin-2-ylamine Gib 1,3-dihydro-indole-2-one 4.12 423.3] \ 1- (4-methoxy-3 _ {[2- (2-fluorene-2,3-dihydro-1H-indole- 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonylamine 5.38 5 2 3.2 N- 4-methyl-3-{[2- (2-fluorene-2,3-diazine-1H-pyridine-5-ylamino) -5-trifluoromethylmonopyrimidin-4-ylamine [] Methyl] -phenylphenyl) -methanesulfonylamine 5.30 5 07.2 5-[4_ (3-methylsulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidine-2- Aminoamino] -1,3-dihydro-indole-2-one 5.14 492.2 5- {4_ [(4-trifluoroacetamido-morpholin-2-ylmethyl) -amino group 5 -tri Fluoromethyl-pyran-2-ylamino} -1,3-dihydro-indiodo-2-one 5.64 5 05.1 -147- 200539871 (145) Compound name HPLC Hysteresis time (minutes) MS data (M + H) 5- {4-[(1-Methanesulfonyl-azetidin-3-ylmethyl) _amino] -5-trifluoromethyl-pyrimidin-2-ylamino}- 1,3 -dihydro-D-D-2 -one 4.76 45 7.2 N-methyl- N- (4-methyl-3-{[2_ (2- 嗣 -2,3 -dihydro-1H- Amino-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonylamine 6.66 521.3 5- {4-[(1_ Methanesulfonyl-pyrrolidin-3-ylmethyl) -amino group] -5 -trifluoromethyl-pyrimidin-2-ylamino group} -1,3 -dihydro-benzene Ketone 4.97 471.2 1 ^ -methyl-1 ^ 1- {3- [2- (2-fluorene-2,3-dichloro-1H-D 5-trifluoromethyl-pyrimidin-4-ylamino] -propyltrimethylsulfonamido 5.02 459.2 5-{4- [2- (1-Methanesulfonyl-?-Nidin-2-ylmethyl) ) -Ethylamino] -5_trifluoromethyl-pyrimidin-2-ylaminob, 1,3-dihydro-Dnadol-2-one 5.71 499.4 5-{4-[(4_methylsulfonyl -D than acryl-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole_2-one 4.68 4 79.1- 148-200539871 (146) Compound name HPLC hysteresis time (minutes) MS data (M + H) {2,2-dimethyl-2- 3- [2- (2-keto-2,3-dihydro-1H- 卩Bow | 5-methylamino) -5 -trifluoromethylmonopyrimidin-4-ylamino] -propyl} -aminocarboxylic acid third butyl ester 7.01 495.0 5-[4- (3- Isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2_one 6.27 410.4 5- {4-[(1-methyl -Naclo-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-D-indol-2 -one 3.71 421.0 5 -{4-[(tetrahydropyran-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- Ketone 5.16 408.3 5-[4- (2-ethyl-butylamino) -5 -trifluoromethyl-pyrimidin-2-ylamine Group] -1,3-dihydro-indole_2-one 6.95 3 94.3 5- {4-[(tetrahydrofuran-2 R-ylmethyl) -amino group] -5 -trifluoromethyl-pyrimidine 2-Aminoaminob 1,3-dihydro-indole-2-one 5.30 394.3 -149- 200539871

(147) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[(四氫呋喃-2S-基甲基）-胺基 ]-5 -三氣甲基-嘧D定-2-基胺基}-1,3 -二氫-吲哚-2-酮 5.30 3 94.3 5 - {4_[(5 -甲基-D夫喃-2-基甲基）-胺 基]-5 -三氣甲基-嘧Π定-2-基胺基}-1，3-二氫-卩引卩朵-2-酮 5.98 404.2 5-{4-[(1-甲磺醯基-吡咯烷-2-基甲 基）-胺基]-5 -三氟甲基-嘧陡-2 -基胺 基}-1，3_二氫-D引D朵-2-酮 5.08 471.3 5-{4_[(金剛院-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二 氫- D引D朵-2 -酮 7.89 458.3 5-{4-[(金剛院-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二 氫-吲哚-2 -酮 5.20 4 73.3 5-[4-(2-甲氧基-2-甲基-丙胺基）-5-三氟甲基-嘧啶-卜基胺基卜1,3-二 氫- D引D朵- 2 -酮 5.87 396.3 5 - {4-[(內-雙環[2.2.1]庚-5-嫌-2- 基 甲基）-胺基]-5 -三氟甲基-喷Π定-2-基 胺基卜1,3 -二氫-D引Β朵-2-酮 6.74 416.3 -150- 200539871 (148) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) (3 - {[2-(2-酮-2,3 -二氫-1H-吲哚-5 -基胺基）-5_三氟甲基-嘧啶-4-基胺 基]-甲基丨-苯甲基）_膦酸二甲酯 5.03 5 2 2.2 5- [4_(3-甲基-丁胺基）_5-三氟甲基-喃Π定-2-基胺基]-1,3-二氫-η引η朵-2-酮 6.87 380.2 5-{4-[(2-羥基-環己基甲基）-胺基]-5-三氟甲基-喃陡-2-基胺基}-1，3-二 氫-吲哚-2-酮 6.66 422.2 1^-（4-甲氧基-3_{[2-(2-酮-2,3-二 氫-1Η-卩引卩朵-5-基胺基）-5-三氣甲 基-喃Π定-4-基胺基]-甲基}-苯基）-Ν -甲基-甲磺醯胺 5.69 5 3 7.2 5 - {4-[(4 -乙磺醯基-嗎啉-2-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1,3_二氫-吲哚-2-酮 5.11 501.3 5 -（4_{[4_(丙-2-擴醯基）-嗎啉-2-基 甲基]-胺基卜5-三氟甲基-嘧啶-2-基 胺基）-1 , 3 -二氫-D引D朵-2 -酮 5.35 515.2 -151 - 200539871 (149) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-{4-[(4_乙醯基-嗎啉-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜 1,3-二氫-吲哚-2-酮 4.43 451.2 5 -{4- [(4-丙酿基-嗎琳-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基}-1,3-二氫-吲哚-2-酮 4.74 465.2 5 -（4-{[4-(2,2-二甲基 ~~丙釀基）-嗎 啉-2-基甲基]-胺基卜5-三氟甲基-嘧 陡-2-基胺基）-1,3 -二氫-D引U朵_2-酮 5.43 493.2 2 - {[2-(2-_ - 2,3 -二氫-1H -卩引卩朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺 基]-甲基卜嗎啉-4-甲酸甲酯 5.04 467.2 5-{4-[(4 -甲氧基乙醯基-嗎啉-2-基 甲基）-胺基]_5_三氟甲基-嘧D定-2-基 胺基卜1,3_二氫-吲哚-2-酮 4.44 481.2 5 - [4_(3_乙磺醯基-苯甲胺基）-5-三 氟甲基-嘧啶-2-基胺基]-1,3-二氫-口引D朵-2-酮 5.36 492.3 5-{4-[(4-甲磺醯基-嗎啉-2 R-基甲基 )_胺基]_5_三氟甲基-嘧啶-2-基胺基 } - 1 , 3 -二氫-D引 D朵-2 - 酮 4.84 48 7.3 -152- 200539871(147) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4-[(tetrahydrofuran-2S-ylmethyl) -amino] -5 -trifluoromethyl-pyridine D-2 -Ylamino} -1,3-dihydro-indole-2-one 5.30 3 94.3 5-{4 _ [(5-methyl-D-furan-2-ylmethyl) -amino] -5- Trigas methyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one 5.98 404.2 5- {4-[(1-methylsulfonyl-pyrrolidine- 2-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidine-2 -ylamino} -1,3-dihydro-D-di-2-one 5.08 471.3 5- {4_ [ (King Kong Yuan-2-ylmethyl) -amino group] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-D-D-2-2-one 7.89 458.3 5- { 4-[(King Kong Yuan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2 -one 5.20 4 73.3 5 -[4- (2-Methoxy-2-methyl-propylamino) -5-trifluoromethyl-pyrimidine-pyridylaminophenyl 1,3-dihydro-D-dihydro-2 -one 5.87 396.3 5-{4-[(Inner-bicyclo [2.2.1] hept-5-an-2-ylmethyl) -amino] -5 -trifluoromethyl-pentin-2-ylamino group 1,3-Dihydro-D-Bind-2-one 6.74 416.3 -150- 200539871 (148) Compound name HPLC hysteresis Time (minutes) MS data (M + H) (3-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5_trifluoromethyl-pyrimidine -4-Aminoamino] -methyl 丨 -benzyl) dimethyl phosphonic acid 5.03 5 2 2.2 5- [4_ (3-methyl-butylamino) _5-trifluoromethyl-amino -2-ylamino] -1,3-dihydro-n-indol-2-one 6.87 380.2 5- {4-[(2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoro Methyl-pyran-2-ylamino} -1,3-dihydro-indole-2-one 6.66 422.2 1 ^-(4-methoxy-3 _ {[2- (2-one-2, 3-dihydro-1Η-pyridin-5-ylamino) -5-trifluoromethyl-anhydroquinidine-4-ylamino] -methyl} -phenyl) -N-methyl- Methanesulfonylamine 5.69 5 3 7.2 5-{4-[(4-Ethylsulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino } -1,3_dihydro-indole-2-one 5.11 501.3 5-(4 _ {[4_ (prop-2-propanyl) -morpholin-2-ylmethyl] -aminob 5-tri Fluoromethyl-pyrimidin-2-ylamino) -1, 3 -dihydro-D-D-2 -one 5.35 515.2 -151-200539871 (149) Compound name HPLC Hysteresis time (minutes) MS data (M + H) 5- {4-[(4-Acetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-yl Amino group 1,3-dihydro-indole-2-one 4.43 451.2 5-{4- [(4-Propanyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl -Pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 4.74 465.2 5-(4-{[4- (2,2-dimethyl ~~ propanyl)- Morpholin-2-ylmethyl] -amino group 5-trifluoromethyl-pyrimidin-2-ylamino group) -1,3-dihydro-D-induction _2-one 5.43 493.2 2-{ [2- (2-_-2,3 -dihydro-1H -pyridin-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl morpholine Methyl-4-formate 5.04 467.2 5- {4-[(4-methoxyethenyl-morpholin-2-ylmethyl) -amino] _5_trifluoromethyl-pyrimidine D-2- Aminoamino group 1,3_dihydro-indole-2-one 4.44 481.2 5-[4_ (3_ethanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamine Group] -1,3-dihydro-ortho-D-2-one 5.36 492.3 5- {4-[(4-methylsulfonyl-morpholine-2 R-ylmethyl) _amino] _5_ Trifluoromethyl-pyrimidin-2-ylamino}-1, 3 -dihydro-D-D-2 -one 4.84 48 7.3 -152- 200539871

(150) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5_{4_[(4_甲磺醯基-嗎啉—2S-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1，3_二氫-吲哚-2-酮 4.86 487.3 5_{4-[(喃U定-2-基甲基）-胺基]-5 -三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮 4.53 402.3 5-{4-[(卩比D秦-2-基甲基）_胺基]-5 -三 氟甲基-嘧Π定-2-基胺基卜1,3 -二氫-吲哚-2-酮 4.42 4 0 2.1 N -（4 -氟- 3- {[2-(2 -酮- 2,3 -二氫-1H-吲哚-5_基胺基）-5_三氟甲基-嘧啶_ 4 -基胺基甲基}_苯基）-N-甲基-甲 磺醯胺 5.55 52 3.3 5 - {4-[(1-甲磺醯基-哌啶-3-基甲基 )-胺基]-5 -三氟甲基-喃D定-2-基胺基 }-1，3-二氫-卩引卩朵-2-酮 5.17 48 5.3 5 - {4_[(4_異丁醯基-嗎啉-2-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 卜1，3-二氫-吲Π朵-2-酮 5.03 4 79.2 -153- 200539871(150) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5_ {4 _ [(4_methylsulfonyl-morpholine-2S-ylmethyl) -amino] -5-trifluoromethyl -Pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 4.86 487.3 5_ {4-[(Uranyl-2-ylmethyl) -amino] -5 -trifluoro Methyl-pyrimidin-2-ylaminob, 1,3-dihydro-indole-2-one 4.53 402.3 5- {4-[(卩 比 D 秦 -2-ylmethyl) _amino] -5 -Trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one 4.42 4 0 2.1 N-(4-fluoro-3 3- {[2- (2- -one -2,3 -dihydro-1H-indole-5_ylamino) -5_trifluoromethyl-pyrimidine_ 4 -ylaminomethyl} _phenyl) -N-methyl-methanesulfonyl Amine 5.55 52 3.3 5-{4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5 -trifluoromethyl-rano-D--2-ylamino}- 1,3-dihydro-pyridin-2-one 5.17 48 5.3 5-{4 _ [(4_isobutylfluorenyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl- Pyrimidin-2-ylaminob 1,3-dihydro-indol-2-one 5.03 4 79.2 -153- 200539871

(151) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4-(3,3 - 二甲基-2- 酮-丁胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2 -酮 6.00 408.2 5-[4-(1，2_二甲基-丙胺基）-5 -三氟 甲基-嘧n定-2-基胺基]-1,3 -二氫-D引 哚- 2 -酮 6.65 380.3 5 - [4-(2 -甲氧基-1-甲基-乙胺基）-5 -三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2 -酮 5.57 382.3 5 - {4-[2_(1,卜二酮-1D6-異噻唑烷-2-基）-乙胺基]_5 -三氟甲基-嘧陡-2 -基胺基卜1,3 -二氫朵-2-酮 4.59 45 7.3 5 - [4-(3_甲胺基-丙胺基）-5-三氟甲 基-喃淀-2-基胺基]-1,3 -二氫-D引D朵-2-酮 3.47 381.3 5 -{4-[(卩比陡-3-基甲基）-胺基]-5-三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-D引D朵-2 -酮 4.62 401.3 5 - {4-[(6_甲磺醯基-吡啶-2-基甲基 )_胺基]-5 -三氟甲基-嘧D定-2-基胺基 }-1，3 -二氫-D引 D朵-2- 酮 4.89 4 79.3 •154· 200539871 (152) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-{4-[3-(l，l-二酮-1，I，6 -異噻哇院-2-基）-苯甲胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二氫-D引D朵-2-嗣 5.45 519.2 5-[4_(lR-苯基-乙胺基）-5 -三氟甲 基-嘧Π定-2-基胺基]-1,3 -二氣-D引H朵-2-酮 6.42 414.4 5 -（4-異两胺基-5-三贏甲基-嘧陡-2-基胺基）-1,3-二氫-吲哚-2-酮 5.84 3 52.2 5 -（4R-第二丁胺基-5-三氟甲基-嘧 陡-2 -基胺基）-1,3 -二氫-D引D朵-2-酮 6.22 366.2 5-(4S-第二丁胺基-5-三氟甲基-嘧 陡-2 -基胺基）-1,3-二氫-问丨D朵-2-酮 6.23 366.2 5 - [4-(2-甲胺基-乙胺基）-5-三氟甲 基-嘧陡-2 -基胺基]-1,3 -二氫-D引晚-2-嗣 3.29 36 7.3 5 - [4-(lS-苯基-乙胺基）-5-三氟甲 基-嘧Π定-2-基胺基]-1,3 -二氫-D引晚-2-酮 6.42 414.3 5 - {4-[(2_甲磺醯基甲基-噻唑-4-基 甲基）_胺基]-5 -三氟甲基-嘧B定-2-基 胺基卜1，3 -二氫-D引D朵-2 -酮 4.72 499.3 -155- 200539871(151) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (3,3-dimethyl-2-keto-butylamino) -5-trifluoromethyl-pyrimidine- 2-ylamino] -1,3-dihydro-indole-2 -one 6.00 408.2 5- [4- (1,2-dimethyl-propylamino) -5-trifluoromethyl-pyrimidine 2-ylamino] -1,3-dihydro-D indol-2-one 6.65 380.3 5-[4- (2-methoxy-1-methyl-ethylamino) -5 -trifluoro Methyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -one 5.57 382.3 5-{4- [2_ (1, budione-1D6-isothiazolidine-2-yl ) -Ethylamino] -5 -trifluoromethyl-pyrimido-2 -ylaminob 1,3-dihydrodo-2-one 4.59 45 7.3 5-[4- (3-methylamino-propylamino ) -5-trifluoromethyl-anhydro-2-ylamino group] -1,3-dihydro-D-D-2-one 3.47 381.3 5-{4-[(卩 比 陡 -3-yl (Methyl) -amino group] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-D-D-2-2-one 4.62 401.3 5-{4-[(6_ 甲Sulfonyl-pyridin-2-ylmethyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-Dendor-2-one 4.89 4 79.3 • 154 · 200539871 (152) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- {4- [ 3- (l, l-dione-1, I, 6-isothiawain-2-yl) -benzylamino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3 -Dihydro-D-Di-2--2- 5.45 519.2 5- [4- (lR-phenyl-ethylamino) -5 -trifluoromethyl-pyrimidine-2-ylamino] -1,3 -Digas-D Indole-2-one 6.42 414.4 5-(4-Isodiaminyl-5-triplemethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole -2-one 5.84 3 52.2 5-(4R-second butylamino-5-trifluoromethyl-pyrimidino-2-ylamino) -1,3-dihydro-D 6.22 366.2 5- (4S-Second-butylamino-5-trifluoromethyl-pyrimidino-2-ylamino) -1,3-dihydro-wen 丨 Ddor-2-one 6.23 366.2 5-[ 4- (2-Methylamino-ethylamino) -5-trifluoromethyl-pyrimido-2 -ylamino] -1,3-dihydro-D indole-2- 嗣 3.29 36 7.3 5- [4- (lS-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-Dindol-2-one 6.42 414.3 5- {4-[(2-Methanesulfonylmethyl-thiazol-4-ylmethyl) _amino group] -5 -trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro -D D-2 -ketone 4.72 499.3 -155- 200539871

(153) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 -（4 -丙胺基-5 -三氟甲基-喃D定-2-基胺基）-1，3-二氫-吲哚-2-酮 5.91 3 52.2 5 - [4- (2 -羥基-1-甲基-乙胺基）-5 -三 集甲基-哺Π定-2-基胺基]-1,3 -二氫-吲哚-2-酮 4.49 3 68.2 5-[4_(1-羥甲基-丙胺基）-5-三氟甲 基-嘧陡-2-基胺基]-1,3 -二氫-D引晚-2-酮 4.85 382.2 5 - {4-[(5 -甲磺醯基-吡啶-3_基甲基 )-胺基]-5 -三氟ί甲基-喃卩定-2-基胺基 卜1，3_二氫-D引D朵-2-酮 4.55 479.4 5-{4-[(D比陡-4-基甲基）-胺基]-5-三 氟甲基-喷陡-2-基胺基}_1，3 -二氫-吲哚-2-酮 4.49 401.2 5 - [4-(1,3_二甲基-丁胺基）-5_三氟 甲基-嘧陡-2-基胺基]-1,3 -二氫-D弓丨 哚-2-酮 6.99 394.3 N**異丙基-N- {3~[2-(2 -嗣-2,3-二氮-1Η-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-丙基卜甲磺醯胺 5.12 48 7.3 -156· 200539871(153) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-(4-propylamino-5 -trifluoromethyl-rano-D-2--2-amino) -1,3-dihydro -Indol-2-one 5.91 3 52.2 5-[4- (2-hydroxy-1-methyl-ethylamino) -5 -tris-methyl-pyridin-2-ylamino] -1, 3-dihydro-indole-2-one 4.49 3 68.2 5- [4_ (1-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3- Dihydro-D's late-2-one 4.85 382.2 5-{4-[(5 -Methanesulfonyl-pyridin-3-ylmethyl) -amino] -5 -trifluoro-methyl-anhydrodine 2-Aminoamino group 1,3-dihydro-D-D-D-2-one 4.55 479.4 5- {4-[(D than a steep 4-ylmethyl) -amino] -5-trifluoro Methyl-pentan-2-ylamino} _1,3-dihydro-indole-2-one 4.49 401.2 5-[4- (1,3-dimethyl-butylamino) -5_trifluoro Methyl-pyrimidin-2-ylamino] -1,3-dihydro-D-bendoindol-2-one 6.99 394.3 N ** Isopropyl-N- {3 ~ [2- (2 -fluorene- 2,3-diazepine-l-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylmethanesulfonamide 5.12 48 7.3 -156 · 200539871

(154) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - [4-(IS -經甲基-2 -甲基-丙胺基）-5-三氟甲基-嘧啶-2-基胺基]-1，3-二 氫-D引D朵-2-酮 5.23 3 96.3 N-環己基-N-{3-[2-(2-酮-2,3-二氫-1H -卩弓[卩朵一 5-基胺基）一 5 -三氟甲基一嘧 啶-4_基胺基]-丙基}-甲磺醯胺 6.24 5 2 7.2 5 - [4-(1,2,3,4-四氫萘-1-基胺基）-5-三氟*甲基-嘧卩定-2 -基胺基]-1,3-二 氫-吲哚-2-酮 440.4 7.17 5_{4-[(1_甲磺醯基-吡咯烷- 2S-基甲 基）-胺基]-5-三氟甲基-嘧啶-2-基胺 基}-1,3 -二氫-D引D朵-2-酮 5.07 471.2 5 - {4-[(3 -甲基-噻吩-2 -基甲基）-胺 基]-5-三氟甲基-嘧啶-2-基胺基}-1，3-二氫-卩引卩朵-2-酮 6.18 420.4 5-{4-[(1-甲磺醯基-吡咯烷-3 R-基甲 基）-胺基]-5 -三氟甲基-嘧D定-2-基胺 基卜1,3-二氫-D引D朵_2-酮 4.95 471.2 5 - [4- (2 -經基-1S-苯基-乙胺基）-5_ 三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2 -酮 5.28 4 30.3 -157· 200539871(154) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-[4- (IS-via methyl-2-methyl-propylamino) -5-trifluoromethyl-pyrimidine-2- Aminoamino] -1,3-dihydro-D-D-2--2-one 5.23 3 96.3 N-cyclohexyl-N- {3- [2- (2-one-2,3-dihydro-1H-卩 弓 [卩 朵 一 -5- 基 amino] -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -methanesulfonamide 6.24 5 2 7.2 5-[4- (1,2 , 3,4-tetrahydronaphthalen-1-ylamino) -5-trifluoro * methyl-pyrimidine-2 -ylamino] -1,3-dihydro-indole-2-one 440.4 7.17 5_ {4-[(1_Methanesulfonyl-pyrrolidine-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- D-Di-2-one 5.07 471.2 5-{4-[(3-methyl-thiophene-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one 6.18 420.4 5- {4-[(1-methylsulfonyl-pyrrolidine-3 R-ylmethyl) -amino] -5 -tri Fluoromethyl-pyrimidin-2-ylaminob, 1,3-dihydro-D, D_2_2one 4.95 471.2 5-[4- (2 -Ethyl-1S-phenyl-ethylamino) ) -5_ trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -one 5.28 4 30.3 -157 · 200539871

(155) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4-(2 -經基- IS -甲基-乙胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2 -酮 4.4 9 3 68.3 5 - [4-(lR-經甲基-丙胺基）-5-三氟甲 基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮 4.85 382.2 5 - [4-(1-嘧啶-4-基-乙胺基）-5 -三氟 甲基-喷陡-2-基胺基]-1,3 -二氫-D引 哚-2-酮 4.84 416.3 5 - [4-(1，1-二酮-四氫-1-噻吩-3-基 胺基）- 5 -三氟甲基-嘧淀-2-基胺基]-1，3-二氫-卩引晚-2-酮 4.67 426.3 5-{4-[(1H-咪哗-2 -基甲基）-胺基]-5-三氣甲基-嘧Π定-2-基胺基}-1,3-二 氫-吲哚-2-酮 3.27 390.3 5 - [4_(2_呢卩定-2-基-乙胺基）_5 -三氣 甲基-嘧U定-2-基胺基]-1,3-二氫-吲 D朵-2-酮 3.79 421.4 5 - [4-(異丁基-甲基-胺基）-5-三氟甲 基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮 6.82 380.3 -158- 200539871 (156) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 1^-甲基-1^-(3-{[2-（2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺 5.49 507.4 1^-乙基-1^-(3-{[2-(2-嗣-2,3-二氯-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-甲基}-苯基）-甲磺醯 胺 5.67 521.3 5 - [4_(2_甲磺醯基-苯甲胺基）_5-三 氟甲基-嘧陡-2-基胺基]-1,3 -二氫-D引Π朵-2-酮 5.47 478.2 N- 異丙基-N-(3-{[2_(2 -嗣 _2,3 -二 氫-1H-吲哚-5 -基胺基）一5 -三氟甲 基-嘧啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺 5.81 5 35.3 5-{4-[(3,4,5,6-四氫_214-[1,2’]聯吡 卩定-3-基甲基）_胺基]-5 -三氟甲基-嘧 陡-2-基胺基卜1,3 -二氫-吲D朵-2-_ 5.79 484.3 5 -{4-[(1-嘧、陡-2-基-派B定-3-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 } - 1 , 3 -二氫-D引 11朵-2 -嗣 6.17 485.3 -159- 200539871(155) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (2- (Cyclo-IS-methyl-ethylamino))-5-trifluoromethyl-pyrimidine-2- Aminoamino] -1,3-dihydro-indole-2 -one 4.4 9 3 68.3 5-[4- (lR-transmethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-yl Amine] -1,3-dihydro-indole-2-one 4.85 382.2 5-[4- (1-Pyrimidin-4-yl-ethylamino) -5 -trifluoromethyl-pentan-2- Amino group] -1,3-dihydro-D indol-2-one 4.84 416.3 5-[4- (1,1-dione-tetrahydro-1-thiophen-3-ylamino) -5- Trifluoromethyl-pyrimido-2-ylamino] -1,3-dihydro-pyridin-2-one 4.67 426.3 5- {4-[(1H-imidazol-2-ylmethyl)- Amine] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 3.27 390.3 5-[4_ (2_neridine-2- -Ethylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-inddo-2-one 3.79 421.4 5-[4- (isobutyl- Methyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one 6.82 380.3 -158- 200539871 (156) Compound name HPLC hysteresis time (Min) MS data (M + H) 1 ^ -methyl-1 ^-(3-{[2- (2-keto-2,3-dihydro-1H- Indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine 5.49 507.4 1 ^ -ethyl-1 ^-(3- {[2- (2- 嗣 -2,3-dichloro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl ) -Methanesulfonylamine 5.67 521.3 5-[4_ (2-Methanesulfonyl-benzylamino) _5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D Indole-2-one 5.47 478.2 N-Isopropyl-N- (3-{[2_ (2-嗣 _2,3-dihydro-1H-indole-5 -ylamino)-5 -tri Fluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine 5.81 5 35.3 5- {4-[(3,4,5,6-tetrahydro_214- [1, 2 '] Bipyridin-3-ylmethyl) _amino] -5 -trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-inddo-2--2- 5.79 484.3 5-{4-[(1-Pyrimidine, acryl-2-yl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino}-1 , 3 -dihydro-D 11 -2-嗣 6.17 485.3 -159- 200539871

(157) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-{4-[2R -（1-甲擴醢基-派Π定-2-基）-乙胺基]-5 -三氟甲基-嘧卩定-2-基胺 基卜1,3 -二氫-D引D朵-2-酮 5.70 499.4 5 - {4-[2S-(l-甲磺醯基-呢陡-2-基）-乙胺基]-5 -三氟^甲基-嘧Π定-2-基胺 基}-1,3 -二氫-D引 D朵-2- _ 5.70 499.4 5 - [4-(3-甲硫基-丙胺基）-5-三氟甲 基-喃陡-2-基胺基]-1,3 -二氫-D引晚-2-酮 5.83 398.2 5-[4-(lS-羥甲基_3-甲硫基-丙胺基 )- 5 -三氟甲基-喃卩定-2 -基胺基]-1,3-二氫-吲哚-2-酮 5.02 428.2 5 - [4-(2 -經基_1R_甲基-乙胺基）-5_ 三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2 -酮 4.49 368.3 5 - [4-(1R-經甲基-2-甲基-丙胺基）-5 -三氣甲基-嘧Π定-2-基胺基]-1,3-二 氫-吲哚-2-酮 5.23 396.4 N-乙基 _N_{3-[2-（2-嗣-2,3-二氮-1H-卩引卩朵-5-基胺基）一 5 -三氟甲基一喷 啶-4_基胺基]-丙基}_甲磺醯胺 5.31 473.3 -160· 200539871 (158) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4 - [(1-甲磺醯基-吡咯烷-3R-基甲 基）-胺基]-5-三氟甲基-嘧啶-2-基胺 基}-1，3_二氫-吲哚-2-酮 4.94 471.4 5-[4_(lS-羥甲基-丙胺基）-5 -三氟甲 基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮 4.86 382.3 5 - [4-(3,5-二硝基-苯甲胺基）_5-三 氣甲基-嘧Π定-2-基胺基]_1，3_二氫-卩引D朵-2-酮 6.04 490. 1 N -（2-{[2-(2-酮-2,3-二氫-1H-吲哚-5 -基胺基）_5_三氟甲基-喃淀-4 -基 胺基]-甲基卜苯基）-甲磺醯胺 5.84 493.1 N -異丙基- N-{2-[2-(2-酮-2,3_ 二氫-1 Η-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4_基胺基]-乙基卜甲磺醯胺 5.37 473.3 5-[4_(2_經基-1-苯基-乙胺基）-5-三 氟甲基-嘧啶-2-基胺基]-1，3_二氫-卩引D朵-2-酮 5.29 430.3 5 - [4-(1R-經甲基-3-甲基-丁胺基）-5-三氟甲基-嘧陡-2-基胺基]-1,3-二 氫-吲哚-2-酮 5.59 410.4 -161 - 200539871(157) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- {4- [2R-(1-Methylsulfenyl-Pyridin-2-yl) -Ethylamino] -5- Trifluoromethyl-pyrimidin-2-ylaminob, 1,3-dihydro-D-D-2-one 5.70 499.4 5-{4- [2S- (l-methanesulfonyl-benzyl) -2-yl) -ethylamino] -5 -trifluoro ^ methyl-pyrimidine-2-ylamino} -1,3-dihydro-D-D-2--2- 5.70 499.4 5-[ 4- (3-Methylthio-propylamino) -5-trifluoromethyl-pyran-2-ylamino] -1,3-dihydro-D-indo-2-one 5.83 398.2 5- [4 -(lS-hydroxymethyl_3-methylthio-propylamino)-5-trifluoromethyl-pyridin-2-ylamino] -1,3-dihydro-indole-2-one 5.02 428.2 5-[4- (2-Ethyl_1R_methyl-ethylamino) -5_trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -one 4.49 368.3 5-[4- (1R-Methyl-2-methyl-propylamino) -5 -trifluoromethyl-pyrimidine-2-ylamino] -1,3-dihydro-indole -2-one 5.23 396.4 N-ethyl_N_ {3- [2- (2-fluorene-2,3-diaza-1H-pyridin-5-ylamino) -5-trifluoromethyl Monopentidin-4-ylamino] -propyl} -methanesulfonamide 5.31 473.3 -16020052005871 (158) Compound name HPLC lag time ( Minutes) MS data (M + H) 5-{4-[(1-methylsulfonyl-pyrrolidine-3R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamine } -1,3-dihydro-indole-2-one 4.94 471.4 5- [4_ (lS-hydroxymethyl-propylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1 , 3-dihydro-indole-2-one 4.86 382.3 5-[4- (3,5-dinitro-benzylamino) _5-trifluoromethyl-pyrimidine-2-ylamino] _1,3_dihydro-pyridin-2-one 6.04 490. 1 N-(2-{[2- (2-one-2,3-dihydro-1H-indole-5 -ylamino) ) _5_trifluoromethyl-anodo-4 -ylamino] -methylphenylphenyl) -methanesulfonylamine 5.84 493.1 N -isopropyl- N- {2- [2- (2-one- 2,3_ dihydro-1 fluorene-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4_ylamino] -ethylsulfamelam 5.37 473.3 5- [4_ (2 _Ethyl-1-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3_dihydro-pyridin-2-one 5.29 430.3 5-[ 4- (1R-Methyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one 5.59 410.4 -161-200539871

(159) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4-(IS-經甲基-3-甲基-丁胺基）-5 -三氟甲基-喃D定-2-基胺基]-1,3-二 氫-D引D朵-2-酮 5.59 410.4 5 - {4-[(1-甲磺醯基-哌啶-2S-基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1,3-二氫-卩引晚-2-酮 5.16 485.3 5-{4-[(1-甲磺醯基-吡咯烷_2R-基甲 基）-胺基]-5 -三議甲基-喃陡-2-基胺 基}-1,3 -二氫-D引D朵-2-酮 5.08 471.3 5-[4_(甲基-D比陡-2-基甲基-胺基）-5 -三氟甲基-喷Π定-2-基胺基]-1,3 -二 氫- D引H朵-2 -酮 5.37 415.3 5 - {4-[(3-甲磺醯基-苯甲基）_甲基-胺基]-5-三氟甲基-嘧啶-2-基胺基}-l,3-二氫-吲哚-2-酮 5.66 492.3 N-甲基-N-(2 - {[2 -（2-酮-2,3-二氫-1 Η-吲哚-5-基胺基）-5_三氟甲基-嘧 陡-4-基胺基]-甲基卜苯基）-甲磺醯 胺 5.63 507.3 -162- 200539871(159) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (IS- via methyl-3-methyl-butylamino) -5 -trifluoromethyl-pyridine 2-ylamino] -1,3-dihydro-D-D-2-one 5.59 410.4 5-{4-[(1-methylsulfonyl-piperidine-2S-ylmethyl) -amine Yl] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one 5.16 485.3 5- {4-[(1-methylsulfonyl-pyrrole Alkane_2R-ylmethyl) -amino] -5 -trisylmethyl-pyran-2-ylamino} -1,3-dihydro-D-D-2--2-one 5.08 471.3 5- [ 4_ (methyl-D than a steep-2-ylmethyl-amino) -5 -trifluoromethyl-pentin-2-ylamino] -1,3-dihydro-D -Keto 5.37 415.3 5-{4-[(3-methylsulfonyl-benzyl) _methyl-amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3- Dihydro-indole-2-one 5.66 492.3 N-methyl-N- (2-{[2-(2-keto-2,3-dihydro-1 fluorene-indole-5-ylamino)- 5-trifluoromethyl-pyrimidino-4-ylamino] -methylphenylphenyl) -methanesulfonamide 5.63 507.3 -162- 200539871

(160) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4_(甲基-B比B定-3_基甲基-胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2-酮 5.25 415.4 5 - {4-[(1_甲磺醯基-呢B定_3_基甲基 )-甲基_胺基]-5-三氟甲基-喃陡_2-基胺基}-1，3 -二氫-D引Π朵-2-酮 5.69 499.4 5 - [4-(甲基-D比π定-4-基甲基-胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-吲哚-2-酮 5.12 415.3 5 -（4-環戊基胺基-5-三氟甲基-嘧 6.47 378.3 Β定-2 -基胺基）-1,3-二氫-D引η朵-2-酮 5 - [4-(2,6 -二甲氧基-苯甲胺基）-5 -三氟甲基-嘧陡-2-基胺基]-1,3-二 氫-吲哚-2-酮 6.78 460.3 5-{4-[(1,5-二甲基-114-吡唑-3-基甲 基卜胺基]-5 -三氟甲基-嘧Π定-2-基胺 基卜1,3-二氫-吲哚-2-酮 4.99 418.3 5 - [4_(2_咪哩-1-基-乙胺基）-5 -三氟 甲基-嘧啶-2-基胺基]-1,3-二氫-吲 哚-2-酮 3.58 404.2 -163- 200539871(160) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4_ (methyl-B than B-Bing-3_ylmethyl-amino) -5-trifluoromethyl-pyrimidine- 2-ylamino] -1,3-dihydro-indole-2-one 5.25 415.4 5-{4-[(1-methylsulfonyl-benzidine-3-ylmethyl) -methyl_ Amino group] -5-trifluoromethyl-anstino-2-ylamino group} -1,3-dihydro-D-indol-2-one 5.69 499.4 5-[4- (methyl-D ratio π Amine-4-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one 5.12 415.3 5-(4-cyclopentyl Aminoamino-5-trifluoromethyl-pyrimidine 6.47 378.3 Beta-2 -ylamino) -1,3-dihydro-D-indo-2-one 5-[4- (2,6-di Methoxy-benzylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one 6.78 460.3 5- {4-[(1 , 5-dimethyl-114-pyrazol-3-ylmethylimido] -5 -trifluoromethyl-pyrimidin-2-ylaminoimido 1,3-dihydro-indole-2 -Keto 4.99 418.3 5-[4_ (2_imid-1-yl-ethylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -Ketone 3.58 404.2 -163- 200539871

(161) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[(啦D定-2-基甲基）-胺基]-5-三 氟甲基-喃Π定-2-基胺基}_1,3 -二氫-D引D朵-2-酮 4.95 401.4 5 - [5-三氟甲基-4-(2-三氟甲基-苯甲 胺基）-嘧陡-2_基胺基]-1,3 -二氫- 口引 哚- 2 -酮 6.57 468.2 5- {4-[(3-甲基-卩比陡-2-基甲基）-胺 基]-5 -三氟ί甲基-啼B定-2_基胺基}-1,3-二氫-吲哚-2-酮 6.07 415.3 5 - [4-(3-甲磺醯基-苯甲胺基）-5-三 氟甲基-嘧Π定-2-基胺基]-1,3 -二氫-吲哚-2-酮 5.16 4 78.2 5-{4-[2-(1_乙酿基-呢陡-2 -基）-乙 胺基]-5 -三氟（甲基-喃陡-2-基胺基}-1，3-二氫-11引晚-2-酮 5.22 4 6 3.4 5_{4-[2-(1-丙醯基-哌陡-2 -基）-乙 胺基]-5 -三氟甲基-喃Π定-2-基胺基}-1，3 -二氫-吲Π朵-2 -酮 5.65 4 7 7.4 5 - {4-[2-(1-環丙院嫉基-呢Π定-2-基 )-乙胺基]-5 -三氟甲基-嚼卩定-2 -基胺 基} - 1，3 -二氫-D引D朵-2 -酮 5.86 489.4 -164- 200539871(161) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4-[(啦 D 定 -2-ylmethyl) -amino] -5-trifluoromethyl-amino -2-ylamino} _1,3-dihydro-D-D-2-one 4.95 401.4 5-[5-trifluoromethyl-4- (2-trifluoromethyl-benzylamino)- Pyridoxine-2_ylamino] -1,3-dihydro-ortho-indole-2 -one 6.57 468.2 5- {4-[(3-methyl-pyridine-2-ylmethyl) -amine Propyl] -5 -trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-indole-2-one 6.07 415.3 5-[4- (3-methylsulfonyl- Benzylamino) -5-trifluoromethyl-pyrimidine-2-ylamino] -1,3-dihydro-indole-2-one 5.16 4 78.2 5- {4- [2- (1 _Ethyl-2-oxo-2-yl) -ethylamino] -5 -trifluoro (methyl-pyran-2-ylamino) -1,3-dihydro-11 5.22 4 6 3.4 5_ {4- [2- (1-Propanyl-piperidin-2 -yl) -ethylamino] -5 -trifluoromethyl-ranyl-2-ylamino} -1 , 3 -dihydro-indodol-2 -one 5.65 4 7 7.4 5-{4- [2- (1-Cyclopropanyl-N-Did-2-yl) -Ethylamino] -5- Trifluoromethyl-leptadin-2 -ylamino}-1,3-dihydro-D-D-2 -one 5.86 489.4 -164- 200539871

(162) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[2-(1-異丁酿基-暖 Π定-2 -基）-乙胺基]-5-三氟甲基-嘧啶-2-基胺 基}-1,3 -二氫-D引D朵-2-酮 6.07 491.3 5-{4_[2-(1- 丁醯基-呢 Π定-2 -基）-乙 胺基]-5-三氛甲基-喃卩定-2-基胺基}-1,3-二氫-吲哚-2-酮 5.99 491.4 5 - {4-[2_(1_甲氧基乙酶基-呢Π定-2-基）-乙胺基]-5-三氟甲基-嘧啶-2-基 胺基卜1,3-二氫-吲哚-2-酮 5.19 493.4 5-{4-[2-(1-環丁烷羰基-哌啶-2-基 )-乙胺基]-5 -三氟甲基-喃B定-2_基胺 基}-1，3-二氫-呼卩朵_2-酮 6.31 503.4 N- 甲基-N-{3 - [2-（2-嗣-2,3-二氯-1H - D弓| D朵-5-基胺基）一5 -三氣甲基-嘧 陡-4-基胺基]-丙基卜乙醯胺 4.47 423.3 N-甲基-N-{3-[2-(2 -嗣 _2,3-二氨-1H-吲哚-5-基胺基）-5_三氟甲基-嘧 啶-4-基胺基]-丙基卜丙醯胺 4.89 437.45 環丙烷甲酸甲基-{3-[2-(2-酮-2,3-二氫-1H -卩引卩朵-5-基胺基）-5 -三氟甲 基-嚼D定-4 _基胺基]-丙基卜醯胺 5.07 449.3 -165- 200539871 (163) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N-甲基-N-{3 - [2-(2 -嗣-2,3-二氨-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-丙基卜異丁醯胺 5.24 451.3 1^-甲基-1^-{3_[2-（2-酮-2,3-二氫-1H-卩弓| H朵-5-基胺基）一5 -三親甲基一嘧 啶-4-基胺基]-丙基卜丁醯胺 5.25 451.4 2-甲氧基-N-甲基- N- {3-[2 -（2-嗣-2,3-二氫-1H-吲哚-5-基胺基）-5-三 親甲基-喷B定-4-基胺基]-丙基}-乙酿 胺 4.47 45 3.3 環丁烷甲酸甲基-{3-[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧Π定-4-基胺基]-丙基}-醯胺 5.48 463.4 2,2，N_ 三甲基-N-{3-[2-(2-嗣-2,3-二氫-1H -卩引卩朵-5-基胺基）-5 -三氟甲 基-嘧Π定-4-基胺基]-丙基}-丙醯胺 5.80 465.3 2，N_二甲基-N-{3-[2-(2-嗣-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧Π定-4 -基胺基]-丙基} - 丁醯胺 5.55 465.3 -166- 200539871(162) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4- [2- (1-Isobutynyl-Ronidine-2 -yl) -ethylamino] -5- Trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-2-one 6.07 491.3 5- {4_ [2- (1-butylfluorenyl-n-pyridin-2-yl) ) -Ethylamino] -5-trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-indole-2-one 5.99 491.4 5-{4- [2_ (1_ Methoxyacetinyl group-? Nidin-2-yl) -ethylamino group] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one 5.19 493.4 5- {4- [2- (1-Cyclobutanecarbonyl-piperidin-2-yl) -ethylamino] -5 -trifluoromethyl-pyranyl-2-ylamino} -1, 3-dihydro-falcon_2-one 6.31 503.4 N-methyl-N- {3-[2- (2-fluorene-2,3-dichloro-1H-D bow | D 朵 -5-yl Amine) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamide 4.47 423.3 N-methyl-N- {3- [2- (2 -fluorene_2,3 -Diamino-1H-indole-5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -propylbupropionamine 4.89 437.45 Cyclopropanecarboxylic acid methyl- {3- [2- (2-keto-2,3-dihydro-1H -pyridin-5-ylamino) -5 -trifluoromethyl-chrysidine-4 -ylamino] -propylbutamidine 5 .07 449.3 -165- 200539871 (163) Compound name HPLC hysteresis time (minutes) MS data (M + H) N-methyl-N- {3-[2- (2 -fluorene-2,3-diamine- 1H-indole-5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -propylbutisobutyramine 5.24 451.3 1 ^ -methyl-1 ^-{3_ [2 -(2-keto-2,3-dihydro-1H-fluorene bow | Hdor-5-ylamino group) -5-triphilemethylmonopyrimidin-4-ylamino group] -propylbutamidine 5.25 451.4 2-methoxy-N-methyl-N- {3- [2-(2-fluorene-2,3-dihydro-1H-indole-5-ylamino) -5-triparent Methyl-pentyl-4-ylamino] -propyl} -ethylamine 4.47 45 3.3 Cyclobutanecarboxylic acid methyl- {3- [2- (2-keto-2,3-dihydro-1H- Indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4-ylamino] -propyl} -fluorenamine 5.48 463.4 2,2, N_trimethyl-N- {3- [2- (2-fluorene-2,3-dihydro-1H -pyridin-5-ylamino) -5 -trifluoromethyl-pyrimidine-4-ylamino] -propyl} -Propanamide 5.80 465.3 2, N-dimethyl-N- {3- [2- [2- (2-fluorene-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoro Methyl-pyrimidine-4 -ylamino] -propyl} -butylamidine 5.55 465.3 -166- 200539871

(164) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 1^-甲基-1^-{3_[2-（2-嗣-2,3-二氨-1H-卩弓|卩朵-5 -基胺基）-5 -三氟甲基-喃 啶-4-基胺基]-丙基}-苯甲醯胺 5.38 4 8 5.3 異噁唑-5 -甲酸甲基-{3-[2-(2 -酮-2,3 -二氫-1H -卩引卩朵-5-基胺基）_5-三 氟》甲基-喷Π定-4-基胺基]-丙基}-醯胺 4.91 4 7 6.2 嗎啉-4-甲酸甲基-{3- [2-(2 -酮_2,3-二氫-1H-卩弓| D朵_5_基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-丙基卜醯胺 4.78 494.3 乙磺酸甲基-{3-[2-(2_酮- 2,3-二氫-1 Η - D弓I D朵一 5 -基胺基）一 5 _三氟甲基一嘧 陡-4-基胺基]-丙基}-醯胺 5.29 47 3.3 丙烷-1-磺酸甲基-{3_[2-(2-酮- 2,3-二氫-1Η-吲哚-5-基胺基）-5-三氟甲 基-嘧Π定-4-基胺基]-丙基}-酿胺 5.71 48 7.3 1，1，3-三甲基-3-{3-[2-(2-酮-2,3-二 氫-1H-吲哚-5-基胺基）一5—三氟甲 基-嘧啶-4-基胺基]-丙基卜磺醯脲 5.53 488.3 -167- 200539871 (165) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 2,2,2_ 三氣-N-甲基- N- {3_[2-(2 -嗣-2,3-二氫-1H-吲哚-5 -基胺基）-5-三 氟甲基-嘧啶—4-基胺基]-丙基}-乙醯 胺 5.80 4 7 7.2 1^-甲基-1^-{2-[2-(2-嗣-2,3-二氮-1H -卩弓| D朵-5 -基胺基）_5-三氟(甲基-喃 Π定-4-基胺基]-乙基}-乙醯胺 4.23 409.2 N-甲基 - N - {2-[2 -（2- 嗣-2,二氯-1 Η-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-乙基卜丙醢胺 4.61 423.2 環丙烷甲酸甲基-{2-[2-(2-酮-2,3 -二氫-1H -卩引D朵-5-基胺基）-5 -三氟甲 基-嘧B定基胺基]-乙基}-醯胺 4.77 43 5.2 N- 甲基-N-{2-[2-(2 -酮 -2,3- 二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-乙基卜異丁醯胺 4.94 43 7.2 N- 甲基-N-{2-[2-（2-酮-2,3-二氫-1H - D引D朵-5 -基胺基）-5 -三氟甲基-嘧 Π定*~4-基胺基]-乙基} - 丁醯胺 4.95 43 7.2 •168- 200539871 (166) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 2-甲氧基-N-甲基-N-{2 - [2-（2-嗣-2,3 -二氫-1H -卩引卩朵-5-基胺基）-5 -三 氣甲基-嘧、H定-4-基胺基]-乙基丨-乙酸 胺 4.21 439.2 環丁烷甲酸甲基-{2-[2-(2-酮-2,3 -二氫-1H-D引D朵-5-基胺基）-5-三氟甲 基-嘧陡-4-基胺基]-乙基卜醯胺 5.17 449.3 2,2，N -三甲基-1^-{2-[2-（2-嗣-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧陡-4 -基胺基]-乙基卜丙醢胺 5.57 451.4 2，N-二甲基-N-{2-[2-(2-酮-2,3-二 氫-1H -卩弓| D朵一 5-基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-乙基卜丁醯胺 5.26 451.4 N - 甲基-N-{2 - [2 -（2-嗣-2,3-二氯-1H-D弓[卩朵-基胺基）- 5 -三氟甲基-嘧 啶-4-基胺基]-乙基卜苯甲醯胺 4.80 471.3 異噁唑-5 -甲酸甲基-{2-[2-(2 -酮-2,3-二氫-114-卩引卩朵-5-基胺基）-5_三 氟甲基-嘧啶-4-基胺基]-乙基卜醯胺 4.51 462.3 -169- 200539871 (167) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 嗎啉-4-甲酸甲基-{2-[2-(2-酮-2,3-二氫-1H -卩引D朵-5 -基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-乙基卜醯胺 4.41 480.3 1^-甲基-1^-{2-[2-（2-嗣-2,3-二氯-1H -卩引卩朵一 5-基胺基）一5 -三氟甲基一喃 H定-4-基胺基]-乙基}-甲磺醯胺 4.77 445. 1 乙磺酸甲基-（2-[2-(2-酮-2,3-二氫-1H -卩引D朵一 5-基胺基）一 5 -三氟甲基一嘧 Π定-4-基胺基]-乙基}-醯胺 5.03 459.2 丙院-1-擴酸甲基-{2-[2-(2-_-2,3-二氫-1H-D引卩朵-5-基胺基）-5 -三氟甲 基-嘧Π定-4 -基胺基]-乙基}-醯胺 5.44 473.3 1，1，3-三甲基-3-{2-[2-(2-酮-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧B定-4-基胺基]-乙基}-磺酿脲 5.49 474.2 2,2,2-三氟-1\1-甲基-1^-{2-[2-(2-酮-2,3 -二氫_1H_卩引卩朵-5-基胺基）-5 -三 氟甲基-嘧啶-4-基胺基]-乙基卜乙醯 胺 5.49 463.2 -170- 200539871(164) Compound name HPLC hysteresis time (minutes) MS data (M + H) 1 ^ -methyl-1 ^-{3_ [2- (2- 嗣 -2,3-diamino-1H- 卩 弓 | 卩Dota-5 -ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -propyl} -benzamide 5.38 4 8 5.3 Isoxazole-5 -formic acid methyl- {3 -[2- (2-keto-2,3 -dihydro-1H-pyridin-5-ylamino) _5-trifluoro "methyl-pentin-4-ylamino] -propyl } -Fluorenamine 4.91 4 7 6.2 Morpholine-4-carboxylic acid methyl- {3- [2- (2-keto_2,3-dihydro-1H-fluorene bow | 5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamine 4.78 494.3 Methyl ethanesulfonate- {3- [2- (2_one-2,3-dihydro-1)- D-bow ID: a 5 -ylamino group) a 5 _trifluoromethyl monopyridino-4-ylamino group] -propyl} -amidamine 5.29 47 3.3 propane-1-sulfonic acid methyl- {3_ [ 2- (2-keto-2,3-dihydro-1fluorene-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -vinylamine 5.71 48 7.3 1,1,3-trimethyl-3- {3- [2- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -propylsulfenilamide 5.53 488.3 -167- 200539871 (165) Compound name HPLC hysteresis time (minutes Bell) MS data (M + H) 2,2,2_ trigas-N-methyl- N- {3_ [2- (2- -fluorene-2,3-dihydro-1H-indole-5 -ylamine ) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -acetamidine 5.80 4 7 7.2 1 ^ -methyl-1 ^-{2- [2- (2- 嗣- 2,3-diazepine-1H -pyrenium | D-do-5 -ylamino) _5-trifluoro (methyl-amino-pidin-4-ylamino) -ethyl} -acetamido 4.23 409.2 N -Methyl-N- {2- [2-(2-fluorene-2, dichloro-1 fluorene-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Ethylbupropionamine 4.61 423.2 Cyclopropanecarboxylic acid methyl- {2- [2- (2-keto-2,3 -dihydro-1H -Hydroxy-5-ylamino) -5 -trifluoromethyl -Pyrimidinylamino] -ethyl} -amidamine 4.77 43 5.2 N-methyl-N- {2- [2- (2-one-2,3-dihydro-1H-indole-5- Aminoamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethylbupropionamine 4.94 43 7.2 N-methyl-N- {2- [2- (2-one-2 , 3-dihydro-1H-D-D-5 -ylamino) -5 -trifluoromethyl-pyrimidine * ~ 4-ylamino] -ethyl}-Butanidine 4.95 43 7.2 • 168- 200539871 (166) Compound name HPLC hysteresis time (minutes) MS data (M + H) 2-methoxy-N-methyl-N- {2-[2- (2-fluorene-2,3 -di -1H -Hydroxy-5-ylamino) -5 -trifluoromethyl-pyrimidine, H-de-4-ylamino] -ethyl 丨 -acetamide 4.21 439.2 cyclobutanecarboxylic acid methyl- { 2- [2- (2-keto-2,3 -dihydro-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl Butamidine 5.17 449.3 2,2, N -trimethyl-1 ^-{2- [2- (2-fluorene-2,3-dihydro-1H-indole-5-ylamino) -5- Trifluoromethyl-pyrimidino-4 -ylamino] -ethylbupropionamine 5.57 451.4 2, N-dimethyl-N- {2- [2- (2-keto-2,3-dihydro-1H -Hydro bow | D-Dot-5-ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -ethylbutanidine 5.26 451.4 N -methyl-N- {2-[2 -(2-fluorene-2,3-dichloro-1H-D bow [fluorenyl-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethylbenzylamine 4.80 471.3 Isoxazole-5 -formic acid methyl- {2- [2- (2-one-2,3-dihydro-114-pyridin-5-ylamino) -5_trifluoromethyl- Pyrimidin-4-ylamino] -ethylbutanamine 4.51 462.3 -169- 200539871 (167) Compound name HPLC Hysteresis time (minutes) MS data (M + H) Morpholine-4-carboxylic acid methyl- {2- [2- (2-Keto-2,3-dihydro-1H -Hydroxy-5 -ylamino) -5 -trifluoromethyl- Pyrimidin-4-ylamino] -ethylpyramine 4.41 480.3 1 ^ -methyl-1 ^-{2- [2- (2- 嗣 -2,3-dichloro-1H- 卩5-ylamino) -5-trifluoromethyl-mono-H--4-ylamino] -ethyl} -methanesulfonylamine 4.77 445.1 1 methyl ethanesulfonate- (2- [2- ( 2-keto-2,3-dihydro-1H-hydrazine-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl} -fluorenamine 5.03 459.2 Bingyuan-1-propanoic acid methyl- {2- [2- (2 -_- 2,3-dihydro-1H-D indole-5-ylamino) -5 -trifluoromethyl- Pyrimidine-4 -ylamino] -ethyl} -amidamine 5.44 473.3 1,1,3-trimethyl-3- {2- [2- (2-one-2,3-dihydro-1H -Indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl} -sulfonylurea 5.49 474.2 2,2,2-trifluoro-1 \ 1 -Methyl-1 ^-{2- [2- (2-keto-2,3-dihydro_1H_pyridin-5-ylamino) -5 -trifluoromethyl-pyrimidine-4- Amino] -ethylbuthamine 5.49 463.2 -170- 200539871

(168) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4-(2 -經基-乙胺基）-5 -三氟甲基-喷Π定-2-基胺基]-1,3-二氫-D引D朵-2 -酮 4.05 3 54.3 5-（4-環丙基胺基-5-三氟甲基-嘧 啶-2-基胺基）-1,3-二氫-吲哚-2-酮 5.41 3 50.3 5 -（4-環丁基胺基-5-三氟甲基-嘧 啶-2-基胺基）-1,3-二氫-吲哚-2-酮 6.01 364.3 5 - [4-(1,4 -二甲基 _ 戊胺基 甲基-嘧Π定-2-基胺基]-1,3 -二氫-D引 哚- 2 -酮 7.45 408.4 5 - [4_(3_咪唑-1-基-丙胺基）-5-三氟 甲基-喃Π定-2-基胺基]-1,3 -二氫-D弓丨 哚-2-酮 3.77 418.3 5 - [4-(2 -苯氧基-乙胺基）-5 -三氟甲 基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮 6.34 430.3 5-[4-(1-環己基-乙胺基）-5-三氟甲 基-嘧Π定-2-基胺基]-1,3-二氫-D引晚-2-酮 7.61 420.4 -171 - 200539871(168) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (2- (Cyclo-ethylamino))-5- [trifluoromethyl-pentidin-2-ylamino] ] -1,3-Dihydro-D-D-2-2-one 4.05 3 54.3 5- (4-Cyclopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3 -Dihydro-indole-2-one 5.41 3 50.3 5-(4-cyclobutylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole- 2-one 6.01 364.3 5-[4- (1,4-dimethyl-pentylaminomethyl-pyrimidine-2-ylamino] -1,3-dihydro-Dindole-2 -one 7.45 408.4 5-[4_ (3_imidazol-1-yl-propylamino) -5-trifluoromethyl-annidine-2-ylamino] -1,3 -dihydro-D-dodo-2 -Ketone 3.77 418.3 5-[4- (2-phenoxy-ethylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2-one 6.34 430.3 5- [4- (1-Cyclohexyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D's late-2-one 7.61 420.4 -171-200539871

(169) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4_(1-羥甲基- 2,2_二甲基-丙胺基 )-5 -三氟甲基-嘧Π定-2-基胺基]-1,3-二氫-吲哚-2-酮 5.64 410.4 5 - [4-(1-甲氧甲基-丙胺基）-5-三氟 甲基-喃Π定-2-基胺基]-1,3 -二氫-〇引 哚- 2 -酮 5.96 396.3 5 - [4-(節滿-2-基胺基）-5 -三氟甲基-嘧Π定-2-基胺基]- 1,3-二氫-U引D朵-2-酮 6.78 426.4 5 - [4-(1 ,2,3,4 -四氫萘-1-基胺基）-5-三氣甲基-喃卩定-2-基胺基]-1,3 -二 氫-吲哚_2-酮 7.16 440.3 5 -（4-環庚基胺基-5-三氟甲基-嘧 陡-2-基胺基）-1,3 -二氫-B引D朵-2-酮 7.21 406.3 5-{4-[2-(2_酮-咪唑烷-1-基）-乙胺 基]-5-三氟甲基-嘧啶-2-基胺基卜 1，3-二氫-卩引晚-2_酮 4.04 4 22.3 4-[2_(2 -酮- 2,3 -二氫-1H-D 引 D朵-5-基 胺基）-5 -三氣甲基-嘧陡-4-基胺基]-丁酸乙酯 5.65 424.2 -172- 200539871 (170) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - [4-(2 -經基-1-經甲基-乙胺基）-5-三氟甲基-喃卩定_2-基胺基]_1,3 -二 氫-吲哚-2-酮 3.72 3 84.2 5 - [4-(3-羥基-2,3-二甲基-丙胺基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二 氫-D引D朵-2 - P 5.0 9 396.3 5 -{4-[(異色滿-1-基甲基）-胺基]-5-三氟甲基-嘧陡_2-基胺基}-1，3-二 氫-吲哚-2 -酮 6.36 456.3 5 - [4-(4-羥基-1,1-二酮-四氫-1&-噻 吩-3 -基胺基）-5 -三氟甲基-嘧陡-2-基胺基]-1,3 -二氫丨D朵-2-酮 4.42 442.2 5 - [4-(2 -甲氧基-1-甲基-乙胺基）-5-三氣甲基-喃卩定-2-基胺基]-1,3 -二 氫-吲哚-2-酮 5.58 38 2.3 5-[4-(反式-4-甲硫基-四氫-呋喃-3-基胺基）-5_三氟甲基_嘧啶-2-基胺 基]-1,3-二氫-D引D朵-2-酮 5.37 426.3 5 - {4-[反式-2-(喃陡-2-基硫基）-環 戊基胺基]-5-三氟甲基-嘧啶-2-基 胺基}-1，3_二氫-D引D朵-2-酮 6.32 488.3 -173- 200539871 (171) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4-(節滿-1 -基胺基）-5 -三氟甲基-喃Π定-2-基胺基]-1,3 -二氫-D引Π朵-2-酮 6.86 426.3 5 -{4-[2-(2-經基-乙硫基）-乙胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二 氫-吲哚-2-酮 4.66 414.3 5-{4-[2-(卩比Π定_3_基氧基）_丙胺基]-5-三氟（甲基-嘧、卩定-2-基胺基}-1,3 -二 氫-吲哚-2-酮 5.20 445.3 5 - {4-[2-(6 -甲基-Π比Π定-2 -基）-乙胺 基]-5 -三鎮甲基-喃Π定-2-基胺基}-1,3-二氫-吲哚_2-酮 5.00 429.3 5-{4-[(2,3_二氫-苯並[1，4]二氧雜環 己二烯-2-基甲基）-胺基]-5-三氟甲 基-嘧Π定-2-基胺基}-1,3 -二氫-巧丨D朵-2-酮 5.01 4 58.2 5 - {4_[(1-甲基-1H-U比哇-4-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜 1 , 3 -二氫-D引D朵-2 -酮 4.60 404.3 -174- 200539871 (172) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[(4,5,6,7-四氫-苯並噻唑-2-基 甲基）-胺基]-5-三氟甲基-嘧啶-2-基 胺基}-1,3 -二氫-D引Π朵-2-酮 5.93 461.2 5 - [4 -（1- 苯基 - 3 - [1，2,4]三挫 -1-基-丙胺基）-5-三氟甲基-嘧啶-2-基胺 基]_1,3-二氫-吲哚-2-酮 5.24 495.2 5-（4-異丁基胺基-5-三氟甲基-嘧 陡-2 -基胺基）-1,3 -二氫-D引U朵-2-酮 6.12 366.4 5 - [4-(2 -環己基-1-經甲基-乙胺基）-5 -三氟甲基-喃卩定-2-基胺基]-1,3 -二 氫- D引D朵-2 -酮 6.41 450.4 2 - [2-(2-酮- 2,3-二氫-1H-吲哚-5-基 胺基）-5-三氟甲基-嘧陡-4-基胺基]-丙酸乙酯 5.26 396.3 5 -（4-環己基胺基-5-三氟甲基-嘧 Π定-2_基胺基）-1,3 -二氫-吲D朵-2-酮 6.82 392.3 5 - [4-(3 -經基-丙胺基）-5 -三氟甲基-嘧啶-2-基胺基]-1,3-二氫-吲哚-2-酮 4.24 3 68.3 -175- 200539871(169) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (1-hydroxymethyl-2,2-dimethyl-propylamino) -5-trifluoromethyl-pyrimidine Amine-2-ylamino] -1,3-dihydro-indole-2-one 5.64 410.4 5-[4- (1-methoxymethyl-propylamino) -5-trifluoromethyl-ran Π Amine-2-ylamino] -1,3-dihydro-oxindole-2-one 5.96 396.3 5-[4- (Benzan-2-ylamino) -5 -trifluoromethyl-pyrimidine Amine-2-ylamino]-1,3-dihydro-U-D-2-anone 6.78 426.4 5-[4- (1,2,3,4-tetrahydronaphthalen-1-ylamino) -5-trifluoromethyl-pyridin-2-ylamino] -1,3-dihydro-indole_2-one 7.16 440.3 5-(4-cycloheptylamino-5-trifluoromethyl) -Pyrimidin-2-ylamino) -1,3-dihydro-B-D-2-one 7.21 406.3 5- {4- [2- (2_one-imidazolidin-1-yl)- Ethylamino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-pyridine-2_one 4.04 4 22.3 4- [2_ (2 -one-2,3- Dihydro-1H-D D-5-ylamino) -5-trifluoromethyl-pyrimidino-4-ylamino] -ethyl butyrate 5.65 424.2 -172- 200539871 (170) Compound name HPLC Hysteresis time (minutes) MS data (M + H) 5-[4- (2 -Cyclo-1-methyl-ethylamino) -5-trifluoromethyl-pyridin-2-ylamino] _1,3-dihydro-indole-2-one 3.72 3 84.2 5-[4- (3-hydroxy-2,3-dimethyl -Propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-D-2-P 5.0 9 396.3 5-{4-[(Dichromatic full- 1-ylmethyl) -amino] -5-trifluoromethyl-pyrimox-2-ylamino} -1,3-dihydro-indole-2 -one 6.36 456.3 5-[4- (4 -Hydroxy-1,1-dione-tetrahydro-1 & -thiophene-3 -ylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3 -dihydro 丨 D Dor-2-one 4.42 442.2 5-[4- (2-methoxy-1-methyl-ethylamino) -5-trifluoromethyl-pyridin-2-ylamino] -1,3 -Dihydro-indole-2-one 5.58 38 2.3 5- [4- (trans-4-methylthio-tetrahydro-furan-3-ylamino) -5_trifluoromethyl_pyrimidine-2 -Ylamino] -1,3-dihydro-D-D-2--2-one 5.37 426.3 5-{4- [trans-2- (furan-2-ylthio) -cyclopentylamino ] -5-Trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-2-one 6.32 488.3 -173- 200539871 (171) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4- (Branyl-1 -ylamino) -5 -trifluoromethyl-annino-2-ylamino] -1,3-dihydro-D Indole-2-one 6.86 426.3 5-{4- [2- (2-Cyclo-ethylthio) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1, 3-dihydro-indole-2-one 4.66 414.3 5- {4- [2- (fluorene ratio_3_yloxy) _propylamino] -5-trifluoro (methyl-pyrimidine, pyridine 2-ylamino} -1,3 -dihydro-indole-2-one 5.20 445.3 5-{4- [2- (6-methyl-Π 比 Π 定 -2 -yl) -ethylamino ] -5 -Three-town methyl-annino-2-ylamino} -1,3-dihydro-indole_2-one 5.00 429.3 5- {4-[(2,3_dihydro-benzene Ac [1,4] dioxanehexadien-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2-ylamino} -1,3 -dihydro- Diao-2-one 5.01 4 58.2 5-{4 _ [(1-methyl-1H-Ubiwa-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2- Aminoamino group 1, 3 -dihydro-D-D-2-2 -one 4.60 404.3 -174- 200539871 (172) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4-[( 4,5,6,7-tetrahydro-benzothiazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D Indole-2-one 5.93 461.2 5-[4- (1-phenyl-3-[1,2,4] trimethyl-1-yl-propylamino) -5-trifluoromethyl-pyrimidine-2 -base Group] _1,3-dihydro-indole-2-one 5.24 495.2 5- (4-isobutylamino-5-trifluoromethyl-pyrimidino-2-ylamino) -1,3-di Hydrogen-D-O-D-2-one 6.12 366.4 5-[4- (2-cyclohexyl-1-methyl-ethylamino) -5 -trifluoromethyl-pyridin-2-ylamino ] -1,3 -Dihydro-D-D- 2 -one 6.41 450.4 2-[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5- Trifluoromethyl-pyrimidino-4-ylamino] -ethyl propionate 5.26 396.3 5-(4-cyclohexylamino-5-trifluoromethyl-pyrimidine-2_ylamino) -1 , 3 -dihydro-indodo-2-one 6.82 392.3 5-[4- (3-Ethyl-propylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3- Dihydro-indole-2-one 4.24 3 68.3 -175- 200539871

(173) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[2_(4-甲基-1H-咪唑-2-基）-乙 胺基]-5-三氟甲基-嘧啶-2-基胺基}-1,3-二氫-吲哚-2-酮 3.54 418.3 5 - [4-(四氫-呋喃-3-基胺基）-5-三氟 甲基-嘧陡-2-基胺基]-1,3 -二氣-D引 哚- 2 -酮 4.89 38 0.3 5 - [4-(二環丙基甲基-胺基）-5-三氟 甲基-嘧Π定-2-基胺基]-1,3 -二氫-D引 哚- 2 -酮 6.59 404.3 5 - {4 - [2_(5- 甲基-4H - [1,2,4]三嗤-3 -基）-乙胺基]-5 -三氟甲基-嘧陡-2-基 胺基卜1，3_二氫-B引D朵-2-酮 4.00 419.3 5 - [4-(2-乙硫基-乙胺基）-5-三氟甲 基-嘧陡-2-基胺基]-1,3 -二氫-D引晚-2-酮 5.99 398.3 5 - [4-(2-苯氧基-丙胺基）-5-三氟甲 基-喃陡-2-基胺基]-1,3 -二氫-吲D朵-2-酮 6.57 444.2 5 - {4_[(1-乙基-5-酮-卩比略院-3-基甲 基）-胺基]-5 -三氟甲基-喃旋-2-基胺 基}-1，3_二氫-吲哚-2-酮 4.57 4 35.2 -176- 200539871(173) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4- [2_ (4-methyl-1H-imidazol-2-yl) -ethylamino] -5-trifluoromethyl -Pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 3.54 418.3 5-[4- (tetrahydro-furan-3-ylamino) -5-trifluoromethyl -Pyrimidino-2-ylamino] -1,3 -digas-D-indol-2 -one 4.89 38 0.3 5-[4- (dicyclopropylmethyl-amino) -5-trifluoromethyl -Pyrimidin-2-ylamino] -1,3-dihydro-D indol-2-one 6.59 404.3 5-{4-[2_ (5-methyl-4H-[1,2,4 ] Trisino-3 -yl) -ethylamino] -5 -trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-B-D-do-2-one 4.00 419.3 5-[ 4- (2-Ethylthio-Ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D's late-2-one 5.99 398.3 5-[ 4- (2-phenoxy-propylamino) -5-trifluoromethyl-pyran-2-ylamino] -1,3-dihydro-inddo-2-one 6.57 444.2 5-{4_ [(1-ethyl-5-keto-fluorene-3-ylmethyl) -amino] -5 -trifluoromethyl-anhydro-2-ylamino} -1,3-dihydro -Indole-2-one 4.57 4 35.2 -176- 200539871

(174) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-(4-{[l-(2 -甲氧基-乙基）-5 -酮-D比 咯烷-3-基甲基]-胺基卜5-三氟甲基-嘧Π定-2-基胺基）-1,3-二氫-D引D朵-2-酮 4.44 465.2 5-[4-(二苯甲基-胺基）-5 -三氟》甲基-嘧啶-2 -基胺基]-1, 3 -二氫-吲哚- 2 -酮 7.26 4 76.2 5-{4-[2_(1-甲基-1H-U比哇-4-基）-乙 胺基]-5 -三氟甲基-喃卩定-2-基胺基}-1，3 -二氫-D引D朵-2 -酮 4.90 418.3 5 - {4 - [(4-甲基-1H-咪唑-2_基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基}-1，3 -二氫-D引D朵-2 -嗣 3.4 0 404.2 5-{4-[(5-環丙基-1H-吡唑-3-基甲基 )-胺基]-5_三氟甲基-嘧啶-2-基胺基 } - 1，3 -二氫-D弓丨B朵-2 -酮 5.00 4 30.2 5 - {4-[2-(4-甲基-噻唑-5-基）-乙胺 基]_5_三氟甲基-嘧啶-2-基胺基}-1，3 -二氫-D引卩朵-2 -酮 5.18 435.2 -177- 200539871(174) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- (4-{[l- (2-methoxy-ethyl) -5-keto-D than pyrrolidin-3-yl Methyl] -amino group 5-trifluoromethyl-pyrimidine-2-ylamino group) -1,3-dihydro-D-D-2-one 4.44 465.2 5- [4- (diphenyl Methyl-amino) -5 -trifluoro "methyl-pyrimidin-2-ylamino] -1, 3 -dihydro-indole-2 -one 7.26 4 76.2 5- {4- [2_ (1- Methyl-1H-U bival-4-yl) -ethylamino] -5 -trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-D -Keto 4.90 418.3 5-{4-[(4-methyl-1H-imidazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-D-D-2-嗣 3.4 0 404.2 5- {4-[(5-Cyclopropyl-1H-pyrazol-3-ylmethyl) -amino] -5_trifluoromethyl -Pyrimidin-2-ylamino}-1,3 -dihydro-D bow 丨 B 2 -one 5.00 4 30.2 5-{4- [2- (4-methyl-thiazol-5-yl)- Ethylamino] -5_trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D iodo-2 -one 5.18 435.2 -177- 200539871

(175) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-{4-[2-(1Η-苯並咪唑-2-基）-乙胺 基]-5-三氟甲基-喃Π定-2-基胺基}-1,3 -二氫-D引D朵-2-酮 4.39 454.2 5-{4-[(5 -甲基-[1,3,4]噁二唑-2-基 甲基）-胺基]-5-三氟甲基-嘧啶_2-基 胺基卜1,3 -二氫-D引D朵-2-酮 4.25 406.3 5-{4-[(5-苯基-4!~1-[1，2,4]三哩-3-基 甲基）_胺基]_5_三氟甲基-嘧啶-2-基 胺基卜1，3 -二氣-D引D朵-2 -酮 4.92 4 67.3 5-{4_[(1Η-卩弓[卩朵-2-基甲基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二 氫-吲哚-2 -酮 6.10 439.3 5-{4-[(1，5-二甲基-1H-D比哩基甲 基）-胺基]-5_三氣甲基-嘧D定-2-基胺 基卜1,3-二氫_吲哚-2-酮 4.77 418.3 5 -{4-[(苯並噻哗-2-基甲基）-胺基]-5_三氟甲基-嘧啶-2-基胺基卜1,3-二 氫-吲哚-2-酮 5.77 4 57.2 5-{4_[(3_甲基-異β惡哗-5-基甲基）-胺基]-5 -三戴甲基-嘧Π定-2-基胺基}-1，3 -二氫-D引D朵-2 -酮 5.02 4 05.3 -178- 200539871(175) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- {4- [2- (1Η-benzimidazol-2-yl) -ethylamino] -5-trifluoromethyl- Pyridin-2-ylamino} -1,3-dihydro-D-di-2-one 4.39 454.2 5- {4-[(5-methyl- [1,3,4] oxadiazole -2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine_2-ylamino group 1,3-dihydro-D-D-2-one 4.25 406.3 5- {4- [ (5-phenyl-4! ~ 1- [1,2,4] trimile-3-ylmethyl) _amino] _5_trifluoromethyl-pyrimidin-2-ylamino group 1,3- Digas-D D-2-2 ketone 4.92 4 67.3 5- {4 _ [(1Η- 卩 弓 [卩 朵 -2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2- Aminoamino group 1,3-dihydro-indole-2 -one 6.10 439.3 5- {4-[(1,5-Dimethyl-1H-D specific methyl group) -amino group] -5_ Three gas methyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one 4.77 418.3 5-{4-[(benzothiazol-2-ylmethyl) -amine Group] -5_trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one 5.77 4 57.2 5- {4 _ [(3_methyl-isoβ 5-ylmethyl) -amino] -5 -trimethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-2 -one 5.02 4 05.3 -178- 200539871

(176) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + Η) 5 - {4-[(4-甲基-噻嗤-2 -基甲基）-胺 基]-5-三氟甲基-喃Π定-2 -基胺基}-1，3 -二氫-D引D朵-2 -酮 5.12 421.2 5-{4-[1_(4 -甲基-噻哗-2 -基）-乙胺 基]-5-三氟甲基-喃Π定-2-基胺基}-1，3-二氫-卩引1]朵-2-酮 5.62 43 5.2 5-{5 -三氟甲基-4-[(1,3,5_三甲基-1Η -卩比Π坐-4-基甲基）-胺基]-5 -三氟 甲基-嘧Π定-2-基胺基}-1,3-二氫-D引 哚- 2 -酮 4.95 432.2 5 - {4-[1-(2 -甲基-噻唑-4-基）-乙胺 基]-5-三氟甲基-嘧卩定-2-基胺基}-1,3-二氫-吲哚-2-酮 5.69 4 35.3 5- {4-[(3-甲基-咪唑並[2,1-b]噻唑- 6- 基甲基）-胺基]-5 -三氟甲基-嘧卩定-2-基胺基卜1，3_二氫-D引D朵-2-酮 5.03 460.3 5 - {4 - [1-（5-甲基- 4H-[1,2,4]三唑-3 -基）-乙胺基]-5-三氟甲基-嘧啶-2-基 胺基} - 1，3 -二氫-D引D朵-2 -酮 4.20 419.3 -179- 200539871(176) Compound name HPLC hysteresis time (minutes) MS data (M + hydrazone) 5-{4-[(4-methyl-thizone-2 -ylmethyl) -amino] -5-trifluoromethyl -Nanthidine-2 -ylamino} -1,3-dihydro-D-D-2-2 -one 5.12 421.2 5- {4- [1_ (4-methyl-thiabap-2-yl)- Ethylamino] -5-trifluoromethyl-pyridin-2-ylamino} -1,3-dihydro-pyridine 1] Dor-2-one 5.62 43 5.2 5- {5 -trifluoromethyl Methyl-4-[(1,3,5-trimethyl-1Η-fluorene ratio π-4-ylmethyl) -amino group] -5 -trifluoromethyl-pyrimidine-2-ylamino group } -1,3-dihydro-D indol-2-one 4.95 432.2 5-{4- [1- (2-methyl-thiazol-4-yl) -ethylamino] -5-trifluoromethyl -Pyrimidin-2-ylamino} -1,3-dihydro-indole-2-one 5.69 4 35.3 5- {4-[(3-methyl-imidazo [2,1-b] thiazole -6-Methyl) -amino] -5 -trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-D-di-2-one 5.03 460.3 5-{4 -[1- (5-methyl-4H- [1,2,4] triazol-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino}-1, 3 -dihydro-D-D-2 -one 4.20 419.3 -179- 200539871

(177) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4 - [1-(3,5 -二甲基-1H-D比哩 _4- 基 甲基）_乙胺基]-5-三氟甲基-嘧啶-2 -基胺基卜1,3-二氫-吲哚-2-酮 5.02 432.3 5 - {4-[2-(3,5_ 二甲基-1H-吡唑-4-基 甲基）_乙胺基]-5 -三氟甲基-喃Π定-2-基胺基卜1,3-二氫-吲哚-2-酮 4.85 432.4 5 - {4-[2-(4,6-二甲基-喃陡-2-基）-乙胺基]-5-三氟甲基-嘧啶-2-基胺 基卜1,3-二氫-吲哚-2-酮 5.17 444.4 5 - {4-[2_(4-甲基 _5,6,7,8-四氫-咱唑 啉-2 -基）_乙胺基]-5-三氣甲基-喃 B定-2-基胺基}-1,3 -二氫-D引D朵-2-酮 5.88 484.4 5 - [4-(2-噻唑_4_基-乙胺基卜5-三氟 甲基-嘧啶-2-基胺基]-1,3-二氫-吲 卩朵-2-_ 5.18 421.3 5 -（4_二甲基胺基-5-三氟甲基-嘧 啶-2_基胺基）_ 1,3-二氫-吲哚-2-酮 5.60 3 38.3 5 - {4_[(1_喃陡基-哌U定基-3-基甲 基）-胺基]-5 -三氟甲基-喃陡-2-基胺 基丨-1 , 3 -二氫-D引D朵-2 -酮 6.17 485.4 -180- 200539871 (178) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5_[4-(茚滿-1-基胺基）-5-三氟甲基-嘧啶-2-基胺基]_1,3_二氫-吲哚-2-酮 6.8 5 426.3 N -甲基-N-{3-[({甲基-[2-(2-酮-2,3_ 二氫-1H -卩引卩朵-5-基胺基）-5-三氟甲 基-嘧啶-4-基]-胺基})-甲基]-苯基 }-甲磺醯胺 6.08 521.3 N-甲基-N-{4-甲基-3-[({甲基-[2 -(2-酮-2,3_二氣-1H - Π引D朵-5-基胺基 )- 5 -三氟甲基-嘧、陡-4-基]-胺基})-甲基]-苯基卜甲磺醯胺 6.24 5 3 5.8 N-(5 -甲基-2_{[2-(2 -酮-2,3 -二氫-1 Η-吲哚-5-基胺基）一 5-三氟甲基一嘧 啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺 6.23 507.2 Ν-(3 -甲基-2-{[2-(2 -酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 啶- 4-基胺基]-甲基}-苯基）-甲磺醯 胺 6.28 507.2 -181 - 200539871 (179) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N -（4 -甲基-2-{[2-(2 -酮-2,3 -二氫-1H_卩引卩朵-5-基胺基）- 5 -三氣甲基-嘧 啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺 6.12 5 0 7.3 1\1-（2-甲基-6-{[2-(2-酮-2,3-二氫-1H-D引卩朵-5-基胺基）_5-三氣甲基-嘧 啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺 5.71 507.3 5 - [4-(3-甲磺醯基-丙胺基）-5-三氟 甲基-嘧Π定-2-基胺基]_1，3 -二氫-D引 哚-2-酮 4.42 430.4 N-甲基-N-（5- 甲基-2_{[2 -（2-嗣-2,3-二氫-114-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基 )-甲磺醯胺 5.95 521.2 N -（3 -甲磺醯基胺基-5-{[2-(2 -酮-2,3-二氫-11^-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基 )-甲磺醯胺 4.85 586.2 -182- 200539871 (180) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N - 甲基-N-(4-甲基-2 - {[ 2 - (2 -嗣-2,3-二氫-1^1-吲哚-5-基胺基）-5-三 氟甲基-嘧啶_4_基胺基]-甲基}_苯基 )-甲磺醯胺 5.87 521.3 N-甲基 _Ν-(2-甲基 -6 -{[2-（2-嗣-2,3-二氫-114-卩引噪-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基}-苯基 )-甲磺醯胺 5.86 521.3 N-甲基-N-（3-甲基-2-{[2-（2-嗣-2,3-二氫-1?^-卩引卩朵-5-基胺基）-5-三 氟甲基-喃陡_4 -基胺基]-甲基}_苯基 )-甲磺醯胺 5.97 521.3 5-{4-[((lS，2R)-2 -經基-環己基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1，3-二氫_卩引11朵-2-酮 5.56 422.3 5-[4-((lR,2S)_2_羥基-節滿-1-基胺 基）-5-三氟甲基-嘧啶-2-基胺基]-1,3-二氫-D引D朵-2-酮 5.66 442.4 5-[4_((S)-l-經甲基_2_苯基-乙胺基 )- 5 -三氟甲基-畴H定-2-基胺基]-1,3-二氫-D引D朵-2 -酮 5.54 444.3 -183- 200539871 (181) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N-（3-(甲擴基-甲基-胺基）-5_{[2-(2-酮-2,3-二氫-1H - D引D朵-5-基胺基 )- 5-三氟甲基-嘧啶-4-基胺基]-甲基 }-苯基）-N-甲基-甲磺醯胺 5.36 614.2 5 - {4-[(1-羥基-環戊基甲基）-胺基]-5-三氟甲基-嘧Π定-2-基胺基}-1，3 -二 氫- D引D朵-2 -酮 5.2 408.2 1^-甲基-1^1-(3-{[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧 Π定-4 -基胺基]-甲基}-卩比Π定-2-基）-甲 磺醯胺 5.26 508.2 N-(3_ 氟-2-{[2-(2_ 酮- 2,3-二氫-1H -吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]•甲基}-苯基）-N_甲基-甲 磺醯胺 5.86 5 2 5.2 5 - {4-[2_((S)_1_甲擴醯基-啦略院-2-基）_乙胺基]_5-三氟甲基-嘧啶-2-基胺基}-1，3 -二氫-D引D朵-2-酮 5.32 4 8 5.4 5-{4_[(卜羥基-環丁基甲基胺基]-5-三氟甲基-嘧啶-2-基胺基卜1,3-二 氫-吲哚-2-酮 4.91 3 94.3 -184- 200539871 (182) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5 - {4-[2-((R)-l_甲磺醯基-吡咯烷-2-基）-乙胺基]-5 -三氟甲基-赌H定-2-基胺基卜1,3 -二氫-n引π朵-2-酮 5.32 48 5.4 N -（2- 氣-6-{[2 -（2 -嗣-2,3 -二氯-1H-口引卩朵-5-基胺基）-5 -三氟甲基-嘧卩定-4-基胺基]-甲基}-苯基）-N-甲基-甲 磺醯胺 5.92 52 5.2 N -（4-氟-2-{[2 -（2-_ - 2,3 -二氫-1H-吲哚-5-基胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基}_苯基）_N_甲基-甲 磺醯胺 5.78 52 5.3 1^-甲基-?^-（4-{[2-(2-酮-2,3-二氫-1 Η-吲哚-5-基胺基）-5-三氟甲基-嘧 陡-4_基胺基]-甲基}-卩比陡-2-基）-甲 磺醯胺 5.17 508.1 N -{2,2 -二甲基-3 - [2-(2 -酮-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-喃陡-4-基胺基]-丙基卜N-甲基-甲磺醯胺 5.7 48 7.3 -185- 200539871 (183) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N -甲基-N-(6_{[2 -（2-酮 -2,3-二氫-1H-卩弓| D朵-5-基胺基）一5-三氟甲基一嘧、 啶-4-基胺基]-甲基卜吡啶-2-基）-甲 磺醯胺 5.61 5 08.2 N-(2,4-二氣-6-{[2-(2-酮-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基·"嘧陡-4-基胺基]-甲基卜苯基） 甲基-甲磺醯胺 5.98 543.2 5 - [4-((R)-l -甲磺醯基-哌D定-3-基胺 基）-5 -三氣甲基-喃Π定-2-基胺基]-1,3-二氫-吲哚_2-酮 5.24 471.3 N- 甲基-N-(6- 甲基-3_{[2_(2-嗣-2,3-二氫-114-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基}-吡 陡-2_基）-甲確醯胺 5.58 522.2 N*~ 甲基-N-(5-{[2_(2 -嗣-2,3 -二氨-1H-B弓[D朵一 5-基胺基）一 5 -三氟甲基一嘧 D定_4_基胺基]-甲基}-卩比U定-3-基）-甲 磺醯胺 4.79 508.2 -186- 200539871 (184) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 5-[4_(1 -甲擴醯基-呢Π定-4-基胺基）-5-三截甲基-嘧H定-2_基胺基]-1,3-二 氫-吲哚-2-酮 5.26 471.2 5-{4_[甲基- ((R)-1-苯基-乙基）-胺基 ]-5 -三氟甲基-喃陡_2_基胺基}-1，3-二氫-吲哚-2-酮 7.23 428.3 5 -（4 -苯甲胺基-5 -三氟甲基-嘧卩定-2 -基胺基）-1,3 -二氫-D引D朵-2-調 6.05 400.3 1^1-（4,6-二甲基-3-{[2-（2-酮-2,3-二 氫一 1H-卩弓1 B朵一 5-基胺基）一 5 -三氟甲 基-嘧、Π定-4-基胺基]-甲基}-批Π定-2-基）-Ν-甲基-甲磺醯胺 6.1 5 36.3 5-（4 -第三丁基胺基-5-三氣甲基-嘧 陡-2-基胺基）-1,3 -二氫-吲D朵-2-調 6.49 3 66.2 5 - [4 -（（1R,5S,6S)-3-甲磺醯基-3-氮 雜-雙環[3.1.0]己-6-基胺基）-5-三 氟甲基-嘧、Π定-2-基胺基]-1,3-二氫-吲哚-2-酮 4.9 9 4 69.3 N- 甲基-N-{3 -甲基 _3-[2-(2-嗣 _2,3-二氫-1H -卩引卩朵-5-基胺基）_5 -三氟甲 基-嘧啶-4-基胺基]-丁基卜甲磺醯胺 5.7 48 7.2 -187- 200539871 (185) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N -（6-甲基-3-{[2-（2-嗣-2,3-二氨-1 Η-吲哚一5-基胺基）一5-三氟甲基一嘧 陡-4 -基胺基]-甲基卜卩比Π定-2 -基）-甲 磺醯胺 5.27 5 08.2 5 - {4-[(2_甲磺醯基-卩比陡-4_基甲基 )-胺基]-5-三氟甲基-嘧啶-2-基胺基 }-1，3 -二氫-D引 D朵-2-酮 4.79 479 2 - [2-(2-嗣-2,3 -二氫-1H-D引 D朵-5- 基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-乙磺酸醯胺 4.19 417.1 N -（3-{甲基-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5_三氟甲基-嘧啶-4-基]-胺基丨-丙基）-甲磺醯胺 5.07 459.3 N -（2-{甲基-[2-（2_ 酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基]-胺基卜乙基）_甲磺醯胺 4.89 445.3 5 - [4-(2_甲磺醯基甲基-苯甲胺基）-5 -三氟甲基-嘧啶-2-基胺基]-1，3-二 氫-吲哚-2-酮 5.38 492,3 -188· 200539871 (186) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 2-[2-(2 -嗣- 2,3 -二氨-1H-D 引卩朵-5- 基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-乙磺酸二甲醯胺 5.09 445.2 N -甲基-N-（3 - {[2 -（2-酬 -2,3-二氯-1H-卩引卩朵-5 -基胺基卜5 -三氟甲基-嘧 H定-4-基胺基]-甲基}-卩比嚷-2-基）-甲 磺醯胺 5.49 509.2 乙磺酸甲基-(2-{[2-(2-酮-2,3-二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-甲基}-苯基）-醯 胺 5.96 521.3 乙擴酸（2-{[2-(2 -酮-2,3 -二氫-1H-U引卩朵-5-基胺基）-5 -三氟甲基-喃陡-4_基胺基]-甲基卜苯基）_醯胺 6.23 507.2 1^-乙基-1^-(3-{[2-(2-酮-2,3-二氫-1H-卩引卩朵-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-甲基卜吡啶-2-基）-甲 磺醯胺 5.54 5 22.2 1^-{1,1-二甲基-3-[2-(2-酮-2,3-二 氣-1H -卩引卩朵-5-基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-丙基卜甲磺醯胺 5.18 4 7 3.1 -189- 200539871 (187) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) ]^-（5,6-二甲基-3-{[2-（2-醒-2,3-二 氫-1H-吲哚-5-基胺基）-5_三氟甲 基-嘧Π定-4-基胺基]-甲基}-卩比曉-2-基）-N-甲基-甲磺醢胺 6.31 5 3 7.1 5 -{4- [((R)-4_甲擴酿基-嗎啉-3-基 甲基）-胺基]-5-三氟甲基-嘧Π定-2-基 胺基}-1,3_二氫-D引D朵-2-酮 4.62 487.2 丙院-1-磺酸（2-{[2-(2-酮-2,3-二 氫-1H - D引D朵-5-基胺基）-5 -三贏甲 基-喷B定-4 -基胺基]-甲基}-苯基）-醯 胺 6.6 521.2 5-{4-[2-((R)-4-甲擴酸基-嗎啉 -3-基）-乙胺基]-5-三氟甲基-嘧啶-2-基 胺基卜1,3 -二氫-吲D朵-2-_ 4.99 501.1 乙磺酸甲基_(3-{[2-(2-酮-2,3-二 氫-1H -吲卩朵-5-基胺基）-5-三氣甲 基-嘧、Π定-4-基胺基]-甲基卜卩比Π定-2-基）-醯胺 5.64 522.2 三氣-N-甲基- N_{3-[2_(2-嗣-2,3 -二 氫-1H -卩引D朵-5-基胺基）_5 -三氣甲 基-嘧啶-4-基胺基]-丙基卜甲磺醯胺 6.42 513.3 -190- 200539871(177) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4-[1- (3,5-dimethyl-1H-D specific miles_4-ylmethyl) _ethylamine Yl] -5-trifluoromethyl-pyrimidin-2 -ylaminob 1,3-dihydro-indole-2-one 5.02 432.3 5-{4- [2- (3,5_dimethyl-1H -Pyrazol-4-ylmethyl) _ethylamino] -5 -trifluoromethyl-annino-2-ylaminob 1,3-dihydro-indole-2-one 4.85 432.4 5- {4- [2- (4,6-Dimethyl-pyran-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro- Indole-2-one 5.17 444.4 5-{4- [2_ (4-methyl_5,6,7,8-tetrahydro-oxazoline-2 -yl) _ethylamino] -5-three gases Methyl-Bran-2-ylamino} -1,3-dihydro-D-D-2--2-one 5.88 484.4 5-[4- (2-thiazol-4-yl-ethylamino group 5 -Trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indiodo-2-_ 5.18 421.3 5-(4-dimethylamino-5-trifluoromethyl-pyrimidine -2_ylamino) _ 1,3-dihydro-indole-2-one 5.60 3 38.3 5-{4 _ [(1_Aranyl-piperidin-3-ylmethyl) -amino] -5 -trifluoromethyl-pyran-2-ylamino group-1, 3 -dihydro-D-D-2 -one 6.17 485.4 -180- 200539871 (178) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5_ [4- (indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] _1,3_dihydro- Indole-2-one 6.8 5 426.3 N -methyl-N- {3-[({methyl- [2- (2-keto-2,3-dihydro-1H-pyridin-5-ylamine Group) -5-trifluoromethyl-pyrimidin-4-yl] -amino})-methyl] -phenyl} -methanesulfonylamine 6.08 521.3 N-methyl-N- {4-methyl-3 -[({Methyl- [2-(2-keto-2,3_digas-1H-hydrazine-5-ylamino)-5 -trifluoromethyl-pyrimidine, steep-4-yl ] -Amino})-methyl] -phenylmethanesulfonamide 6.24 5 3 5.8 N- (5-methyl-2 _ {[2- (2-keto-2,3-dihydro-1 fluorene- Indole-5-ylamino) -5-trifluoromethylmonopyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide 6.23 507.2 N- (3-methyl-2- { [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) -Methanesulfonamide 6.28 507.2 -181-200539871 (179) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N-(4-methyl-2-{[2- (2 -one-2, 3 -dihydro-1H_fluorene-5-ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonyl Amine 6.12 5 0 7.3 1 \ 1- (2-methyl-6-{[2- (2-keto-2,3-dihydro-1H-D indole-5-ylamino) _5-three gases Methyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine 5.71 507.3 5-[4- (3-Methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidine Π 定 -2-ylamino] _1,3-dihydro-D indol-2-one 4.42 430.4 N-methyl-N- (5-methyl-2 _ {[2-(2-fluorene-2, 3-dihydro-114-pyridin-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine 5.95 521.2 N- (3-Methanesulfonylamino-5--5-[[2- (2-keto-2,3-dihydro-11 ^ -pyridin-5-ylamino) -5-trifluoromethyl- Pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide 4.85 586.2 -182- 200539871 (180) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N-methyl-N -(4-methyl-2-{[2-(2 -fluorene-2,3-dihydro-1 ^ 1-indole-5-ylamino) -5-trifluoromethyl-pyrimidine_4_ Methylamino] -methyl} -phenyl) -methanesulfonamide 5.87 521.3 N-methyl_N- (2-methyl-6-{[2- (2-fluorene-2,3-dihydro- 114-fluorene-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) -methanesulfonylamine 5.86 521.3 N-methyl-N- (3-methyl-2-{[2- (2-fluorene-2,3-dihydro-1? ^-Pyridin-5-ylamino) -5- Trifluoromethyl-pyridyl-4-ylamino] -methyl} -phenyl) -methanesulfonylamine 5.97 521.3 5- {4-[((lS, 2R) -2 -Ethyl-cyclohexylmethyl ) -Amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-hydrazine 11-2-one 5.56 422.3 5- [4-((lR, 2S ) _2_Hydroxy-benzyl-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-D-di-2-one 5.66 442.4 5- [4-((S) -l-Methyl-2-phenyl-ethylamino) -5 -trifluoromethyl-domain H-di-2-ylamino] -1,3-dihydro-D D-2-2 ketone 5.54 444.3 -183- 200539871 (181) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N- (3- (methyl-epi-methyl-amino) -5 _ {[ 2- (2-keto-2,3-dihydro-1H-D--5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl ) -N-methyl-methanesulfonamide 5.36 614.2 5-{4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2-ylamine Yl} -1,3-dihydro-D-D-do-2-one 5.2 408.2 1 ^ -methyl-1 ^ 1- (3-{[2- (2-keto-2,3-dihydro-1H -Indol-5-ylamino) -5-trifluoromethyl -Pyrimidine-4 -ylamino] -methyl} -pyridine Πidine-2-yl) -methanesulfonylamine 5.26 508.2 N- (3-fluoro-2-{[2- (2_ ketone-2, 3-dihydro-1H -indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] • methyl} -phenyl) -N_methyl-methanesulfonamide 5.86 5 2 5.2 5-{4- [2 _ ((S) _1_Methanyl-Laluoyuan-2-yl) _ethylamino] _5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -dihydro-D-D-2-one 5.32 4 8 5.4 5- {4 _ [(Hydroxy-cyclobutylmethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino 1,3-Dihydro-indole-2-one 4.91 3 94.3 -184- 200539871 (182) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5-{4- [2-((R ) -l-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5 -trifluoromethyl-H-di-2-ylamino group 1,3 -dihydro-n -2-one 5.32 48 5.4 N-(2- qi-6-{[2-(2 -fluorene-2,3 -dichloro-1H-ordinary-5-ylamino) -5 -trifluoro Methyl-pyrimidin-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide 5.92 52 5.2 N-(4-fluoro-2-{[2-(2- _-2,3 -dihydro-1H-indole-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} _phenyl) _N_formyl -Methanesulfonylamine 5.78 52 5.3 1 ^ -methyl-? ^-(4-{[2- (2-keto-2,3-dihydro-1 fluorene-indole-5-ylamino)- 5-trifluoromethyl-pyrimidino-4-ylamino] -methyl} -pyridoxan-2-yl) -methanesulfonylamine 5.17 508.1 N-{2,2-dimethyl-3-[ 2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-rando-4-ylamino] -propylbenzene N-methyl -Methanesulfonamide 5.7 48 7.3 -185- 200539871 (183) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N -methyl-N- (6 _ {[2-(2-keto-2, 3-dihydro-1H-fluorene bow | Ddor-5-ylamino) -5-trifluoromethylmonopyrimidin, pyridin-4-ylamino] -methylpyridin-2-yl) -methanesulfonate Amidine 5.61 5 08.2 N- (2,4-Digas-6-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl &Quot; pyrimidino-4-ylamino] -methylphenylphenyl) methyl-methanesulfonylamine 5.98 543.2 5-[4-((R) -1 -methanesulfonyl-piperidine)- 3-ylamino) -5 -trifluoromethyl-anhydro-2-dino-2-ylamino] -1,3-dihydro-indole_2-one 5.24 471.3 N-methyl-N- (6- Methyl-3 _ {[2_ (2-fluorene-2,3-dihydro-114-fluorenyl-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl Yl} -pyridine -2_yl) -Methylchloramine 5.58 522.2 N * ~ Methyl-N- (5-{[2_ (2-(2 -3-2,3 -Diamino-1H-B) )-5 -trifluoromethyl-pyrimidinyl_4_ylamino] -methyl} -pyridinium-Udin-3-yl) -methanesulfonylamine 4.79 508.2 -186- 200539871 (184) Compound name HPLC hysteresis time (minutes) MS data (M + H) 5- [4_ (1-Methylsulfenyl-? Nidin-4-ylamino) -5-trimethyl-pyrimidinyl-2_yl Amine] -1,3-dihydro-indole-2-one 5.26 471.2 5- {4_ [Methyl-((R) -1-phenyl-ethyl) -amino] -5 -trifluoromethyl -Amino-2-anylamino} -1,3-dihydro-indole-2-one 7.23 428.3 5-(4-Benzylamino-5 -trifluoromethyl-pyrimidine-2- Aminoamino) -1,3-dihydro-D-D-di-2-6.06 400.3 1 ^ 1- (4,6-dimethyl-3-{[2- (2-keto-2,3- Dihydro- 1H-pyrenium-1 B- (5-ylamino)-5 -trifluoromethyl-pyrimidine, hydradin-4-ylamino] -methyl} -batch hydradin-2-yl)- N-methyl-methanesulfonylamine 6.1 5 36.3 5- (4-tert-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indD Duo-2-tune 6.49 3 66.2 5-[4-((1R, 5S, 6S) -3-Methanesulfonyl-3-aza-bicyclo [3.1.0] hex-6-yl Yl) -5-trifluoromethyl-pyrimidine, hydradinyl-2-ylamino] -1,3-dihydro-indole-2-one 4.9 9 4 69.3 N-methyl-N- {3-methyl -3- [2- (2-fluorene_2,3-dihydro-1H-pyridine-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -butyl Sulfamethoxamine 5.7 48 7.2 -187- 200539871 (185) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N-(6-methyl-3-{[2- (2- 嗣 -2 , 3-diamino-1 fluorene-indole-5-ylamino) -5-trifluoromethyl-pyrimidino-4-ylamino] -methylbupidinidine-2 -yl) -formyl Sulfonamide 5.27 5 08.2 5-{4-[(2-Methanesulfonyl-pyridyl-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-D-D-D-2--2-one 4.79 479 2-[2- (2-fluorene-2,3-dihydro-1H-D D-D-5-5-ylamino) -5 -Trifluoromethyl-pyrimidin-4-ylamino] -ammonium ethanesulfonate 4.19 417.1 N-(3- {methyl- [2- (2-keto-2,3-dihydro-1H-indole) -5-ylamino) -5_trifluoromethyl-pyrimidin-4-yl] -amino 丨 -propyl) -methanesulfonylamine 5.07 459.3 N-(2- {methyl- [2- (2_ Keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -aminobuethyl) _methanesulfonate Amine 4.89 445.3 5-[4- (2-Methanesulfonylmethyl-benzylamino) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-keto 5.38 492,3 -188 · 200539871 (186) Compound name HPLC Hysteresis time (minutes) MS data (M + H) 2- [2- (2-嗣-2,3 -diamine-1H-D Introduction Amino-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -dimethylsulfonamide ethanesulfonate 5.09 445.2 N -methyl-N- (3-{[2-( 2-amyl-2,3-dichloro-1H-pyridine-5 -ylaminob 5 -trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyrene- 2-yl) -methanesulfonamide 5.49 509.2 methyl ethanesulfonate- (2-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) -fluorenamine 5.96 521.3 Ethane (2-{[2- (2-keto-2,3-dihydro-1H- U-bend-5-ylamino) -5 -trifluoromethyl-anso-4-ylamino] -methylbuphenyl) _amido 6.23 507.2 1 ^ -ethyl-1 ^-( 3-{[2- (2-keto-2,3-dihydro-1H-pyridin-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl Pyridin-2-yl) -methanesulfonylamine 5.54 5 22.2 1 ^-{1,1-dimethyl-3- [2- (2-one-2,3-digas-1H -Pyridol-5-ylamino) -5 -trifluoromethyl-pyrimidin-4-ylamino] -propyltrimethoprim 5.18 4 7 3.1 -189- 200539871 (187) Compound name HPLC Delay time (minutes) MS data (M + H)] ^-(5,6-dimethyl-3-{[2- (2-ake-2,3-dihydro-1H-indole-5-yl Amine) -5_trifluoromethyl-pyrimidin-4-ylamino] -methyl} -fluorenyl-2-yl) -N-methyl-methanesulfonamide 6.31 5 3 7.1 5- {4- [(((R) -4_Methenyl-morpholin-3-ylmethyl) -amino]]-5-trifluoromethyl-pyrimidine-2-ylamino}}-1, 3_Dihydro-D-D-D-2-one 4.62 487.2 Bingyuan-1-sulfonic acid (2-{[2- (2-keto-2,3-dihydro-1H-D-D-D-5- Aminoamino) -5 -trimethylol-pentyl-4 -ylamino] -methyl} -phenyl) -amidinyl 6.6 521.2 5- {4- [2-((R) -4- Methanoate-morpholin-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-inddo-2--2- 4.99 501.1 ethyl Sulfomethyl_ (3-{[2- (2-keto-2,3-dihydro-1H-indiodo-5-ylamino) -5-trifluoromethyl-pyridine, Π 定 -4 -Methylamino] -methylpyridinium-2-yl) -amidinylamine 5.64 522.2 tris-N-methyl-N_ {3- [2_ (2-fluorene-2,3-dihydro-1H -D--5-ylamine ) _5 -trifluoromethyl-pyrimidin-4-ylamino] -propylmethanesulfonamide 6.42 513.3 -190- 200539871

(188) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) 環丙垸擴酸甲基-{3-[2-(2-酮-2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-畴Π定-4-基胺基]-丙基酿胺 5.5 485.3 1^乙基-1^-(2-{[2_(2-酮-2,3-二氫-1 Η-吲哚-5-基胺基）-5-三氟甲基-嘧 Π定-4 -基胺基]-甲基}-苯基）-甲擴醯 胺 5.94 521.2 乙磺酸甲基-(5 -甲基-2-{[2-(2 -酮- 2,3 -二氫-1Η-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯羞 口引D朵-5-η-醯胺 乙擴酸乙基-(2-{[2-(2-酮-2,3-二 氫一 1H-D引D朵一 5_基胺基）一 5 -三贏甲 基-嘧啶-4-基胺基]-甲基卜苯基）-醯 胺 6.22 535 乙磺酸乙基-（5 -甲基-2-{[2-(2-酮-2,3 -二氫-1H -卩引D朵-5-基胺基）-5_三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基 )-醯胺 6.55 549 N-乙基-N-(5-甲基 -2-{[2-(2-酮-2,3-二氫-11^-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基卜苯基 )-甲磺醯胺 6.27 5 3 5.1 -191 - 200539871 (189) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + Η) 乙磺酸（5 -甲基-2-{[2-(2-酮-2,3-二 氫一 1H-吲哚一5-基胺基）一5-三氟甲 基-嘧啶_4-基胺基]-甲基卜苯基）-醯 胺 6.59 521.1 乙擴酸（3-甲基-2-{[2-(2-酮-2,3-二 氫一 1H-卩引卩朵一 5-基胺基）一 5 -三氣甲 基-喃陡-4-基胺基]-甲基}-苯基）-酸 胺 6.7 521.3 乙磺酸甲基-(3 -甲基-2-{[2-(2-酮-2,3-二氫-11^-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶—4-基胺基]-甲基}-苯基 )-醯胺 6.33 5 35.2 2 - [2-(2-嗣-2,3 -二氫-1H-D 引 D朵-5- 基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-乙磺酸甲醯胺 4.6 431.1 乙磺酸{3-[2-(2_ 酮- 2,3-二氫-1H-吲 哚-5-基胺基）_5-三氟甲基-嘧啶-4-基胺基]-丙基}-醯胺 4.87 459.1 匸-甲擴醯基-1^_{3-[2-(2-酮-2,3-二 氫一 1H-卩弓| D朵—5-基胺基）-5-三氟甲 基-嘧Π定-4-基胺基]-丙基}-甲擴醯胺 4.84 523 -192- 200539871 (190) 化合物名稱 HPLC 遲滯時間 (分鐘） M S數據 (Μ + Η) 乙磺酸{2-[2-(2-酮-2,3-二氫 _1H-吲 D朵-5 -基胺基）-5-三氟甲基-嘧卩定-4-基胺基]_乙基卜醯胺 4.65 445.2 匸-甲擴酿基-1^-{2-[2-（2-酮-2,3_二 氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-乙基卜甲磺醯胺 4.62 509 N-甲基-N-（4-甲基 - 3-{[2 -（2 - 酬-2,3-二氫-114-卩引卩朵-5-基胺基）-5-三 氟甲基-嘧啶-4-基胺基]-甲基}-吡 啶-2-基卜甲磺醯胺 5.63 5 22.1 5-（4-{[1_(2,2,2_三氟-乙醯基）-呢 啶-3-基甲基]-胺基卜5-三氟甲基-嘧 淀-2 -基胺基）-1,3 -二氫-吲D朵-2-酮 6.04 503.1 2,2,2-三氟-乙磺酸{3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧Π定-4 -基胺基]-丙基卜醯胺 5.56 513.2 N-甲基-N-(4-{[2-(2-酮-2,3-二氫-1H - D弓| D朵-5-基胺基）一5-三氟甲基-嘧、 Π定-4 -基胺基]-甲基卜嘧淀-2 -基）-甲 磺醯胺 5.21 509.3 •193· 200539871 (191) 化合物名稱 HPLC 遲滯時間 (分鐘） MS數據 (M + H) N-環丙基-N-(2-{[2-(2-酮-2,3-二 氫一 1H—D引D朵一 5-基胺基）一5-三氟甲 基-喃Π定-4-基胺基]-甲基}_苯基）-甲 磺醯胺 6.01 5 3 3.3 N- 甲基-N-（2-{[2-（2-嗣-2,3-二氯-1 Η-吲哚-5-基胺基）-5-三氟甲基-嘧 陡_4-基胺基]-甲基卜喃陡_4 -基）-甲 磺醯胺 4.95 509.2 Ν-甲基-Ν_(6-{[2-(2-嗣-2,3-二氫-1Η-卩引卩朵一 5_基胺基）_5-三親甲基一II·密 啶-4-基胺基]-甲基}-吡嗪-2-基）-甲 磺醯胺 5.3 509.4 N-甲基-N-(2-{[2-（2-酮-2,3-二氫-1H - D弓| D朵-5-基胺基）- 5 -三氟甲基-嘧 陡-4-基胺基]-甲基卜卩比D定_3 -基）-甲 磺醯胺 5.54 508.3 N-甲基-N-(3-{[2_(2 -嗣-2,3 -二氨-1H - D引卩朵一 5-基胺基）一 5 -三氟甲基一嘧 陡-4-基胺基]-甲基}-卩比B定-4-基）-甲 磺醯胺 5.55 5 08.4 -194- 200539871 (192) 化合物名稱 HPLC 遲滞時間 (分鐘） MS數據 (M + H) N-環丙基-N-(3-{[2-(2-酮 _2,3-二 氫-1H-吲哚-5-基胺基）_5_三氟甲 基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲磺醯胺 5.6 534.1 N-甲基-N-（6- 甲基-3-{[2-(2-酮-2,3-二氫-1^1-吲哚-5-基胺基）_5-三 氟甲基-嘧啶-4-基胺基]_甲基卜吡 嗪-2-基）-甲磺醯胺 5.93 523.4 5 - {4-[(2-甲擴醯基甲基-Π比U定-3-基 甲基）_胺基]-5-三氟甲基-嘧啶-2-基 胺基卜1,3-二氫-吲哚-2-酮 5.4 493.2 N-甲基-N-(4-{[2-(2 -酮-2,3-二氫-1H_吲哚-5-基胺基）-5-三氟甲基-嘧 啶-4-基胺基]-甲基卜吡啶-3-基甲 磺醯胺 4.77 508.2 -195- 200539871 (193) 所有文中所引用的專利案、申請案、公開案、測試方 法、文獻、及其他材料均全部倂入本文以供參考。(188) Compound name HPLC hysteresis time (minutes) MS data (M + H) Cyclopropanoate methyl- {3- [2- (2-keto-2,3-dihydro-1H-indole-5 -Ylamino) -5-trifluoromethyl-domain din-4-ylamino] -propylamine 5.5 485.3 1 ^ ethyl-1 ^-(2-{[2_ (2-one-2 , 3-dihydro-1 fluorene-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -ylamino] -methyl} -phenyl) -methanesulfonylamine 5.94 521.2 methyl ethanesulfonate- (5-methyl-2-{[2- (2-keto-2,3-dihydro-1fluorenyl-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl benzene benzene benzene D--5-η-amido ethane diacetate ethyl- (2-{[2- (2-keto-2,3-dihydro-1H-D benzene D Dodecyl-5-ylamino) -5-trimethylol-pyrimidin-4-ylamino] -methylbuphenyl) -amidoamine 6.22 535 ethyl ethanesulfonate- (5-methyl-2- {[2- (2-keto-2,3 -dihydro-1H-pyridine-5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylbenzene ) -Fluorenamine 6.55 549 N-ethyl-N- (5-methyl-2-{[2- (2-keto-2,3-dihydro-11 ^ -pyridin-5-ylamine) Group) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonylamine 6.27 5 3 5.1 -191-200539871 (189) Compound name HPLC hysteresis time (minutes) MS data (M + Η) ethanesulfonic acid (5-methyl-2-{[2- (2-keto-2,3-dihydro-1H-indole-5-5-ylamino) ) -5-Trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenylamine 6.59 521.1 Ethanoic acid (3-methyl-2-{[2- (2-one-2 , 3-dihydro-1H-pyridine-5-ylamino) -5-trifluoromethyl-pyran-4-ylamino] -methyl} -phenyl) -acylamine 6.7 521.3 ethyl Sulfomethyl- (3-methyl-2-{[2- (2-keto-2,3-dihydro-11 ^ -pyridin-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -methyl} -phenyl) -amidamine 6.33 5 35.2 2-[2- (2-fluorene-2,3-dihydro-1H-D) Amine) -5-trifluoromethyl-pyrimidin-4-ylamino] -formamidine ethanesulfonate 4.6 431.1 {3- [2- (2_ Ketone-2,3-dihydro-1H- Indole-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -fluorenamine 4.87 459.1 fluorenyl-methanesulfonyl-1 ^ _ {3- [2- ( 2-keto-2,3-dihydro-1H-fluorene bow | D-do-5-ylamino) -5-trifluoromethyl-pyrimidine-4-ylamino] -propyl} -methyl Amidine 4.84 523 -192- 200539871 (190) Compound name HPLC Hysteresis time (minutes) MS data (M + Η ) Ethanesulfonic acid {2- [2- (2-keto-2,3-dihydro_1H-indDido-5 -ylamino) -5-trifluoromethyl-pyrimidine-4-ylamine Yl] -ethylbuminamine 4.65 445.2 fluorenyl-methanyl-1 ^-{2- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino)- 5-trifluoromethyl-pyrimidin-4-ylamino] -ethylbenzamide 4.62 509 N-methyl-N- (4-methyl- 3-{[2-(2- , 3-dihydro-114-pyridin-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyridin-2-ylbusamidine 5.63 5 22.1 5- (4-{[1_ (2,2,2_trifluoro-ethylfluorenyl) -morphin-3-ylmethyl] -aminob 5-trifluoromethyl-pyrimido-2 -Ylamino) -1,3-dihydro-inddo-2-one 6.04 503.1 2,2,2-trifluoro-ethanesulfonic acid {3- [2- (2-keto-2,3-di Hydrogen-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -ylamino] -propylbutamidine 5.56 513.2 N-methyl-N- (4- { [2- (2-keto-2,3-dihydro-1H-D bow | D-do-5-ylamino) -5-trifluoromethyl-pyrimidine, hydradin-4-ylamino] -formyl Jibupyridine-2 -yl) -methanesulfonamide 5.21 509.3 • 193 · 200539871 (191) Compound name HPLC hysteresis time (minutes) MS data (M + H) N-cyclopropyl-N- (2- { [2- (2 -Keto-2,3-dihydro-1H—D-D-mono-5-ylamino) -5-trifluoromethyl-annidine-4-ylamino] -methyl} -phenyl)- Methanesulfonamide 6.01 5 3 3.3 N-methyl-N- (2-{[2- (2-fluorene-2,3-dichloro-1 fluorene-indole-5-ylamino) -5-tris Fluoromethyl-pyrimidino-4-ylamino] -methylpropanyl-4-yl) -methanesulfonamide 4.95 509.2 N-methyl-N_ (6-{[2- (2-fluorene-2 , 3-dihydro-1Η-pyridine-1-5-ylamino group) _5-Triphilemethyl-II · melidin-4-ylamino group] -methyl} -pyrazin-2-yl)- Methanesulfonylamine 5.3 509.4 N-methyl-N- (2-{[2- (2-keto-2,3-dihydro-1H-D bow | D-dosyl-5-ylamino)-5 -tri Fluoromethyl-pyrimidino-4-ylamino] -methylpyridinium-Diodin-3-yl) -methanesulfonylamine 5.54 508.3 N-methyl-N- (3-{[2_ (2-嗣-2,3 -Diamino-1H-D Indole-5-ylamino) -5-trifluoromethyl-pyrimidino-4-ylamino] -methyl} -fluorenyl ) -Methanesulfonylamine 5.55 5 08.4 -194- 200539871 (192) Compound name HPLC Hysteresis time (minutes) MS data (M + H) N-cyclopropyl-N- (3-{[2- (2 -Keto_2,3-dihydro-1H-indole-5-ylamino) __ 5_trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -Methanesulfonylamine 5.6 534.1 N-methyl-N- (6-methyl-3-{[2- (2-keto-2,3-dihydro-1 ^ 1-indole-5-ylamino) ) _5-Trifluoromethyl-pyrimidin-4-ylamino] -methylpyrazin-2-yl) -methanesulfonylamine 5.93 523.4 5-{4-[(2-Methylpyridinylmethyl- Π is better than U-D-3-ylmethyl) _amino group] -5-trifluoromethyl-pyrimidin-2-ylamino group 1,3-dihydro-indole-2-one 5.4 493.2 N-methyl -N- (4-{[2- (2-keto-2,3-dihydro-1H_indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methylpyridin-3-ylmethanesulfonamide 4.77 508.2 -195- 200539871 (193) All patents, applications, publications, test methods, literatures, and other materials cited in this article are hereby incorporated herein by reference. reference.

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Claims (1)

200539871 (1) 十、申請專利範圍 1 · 一種如下式1所示之化合物200539871 (1) 10. Scope of patent application1. A compound represented by the following formula 1 φ 或其藥學上可接受之鹽、溶劑化物、水合物或前驅藥 物， 其中η是1至3之整數； 各個R1是分別選自氫、羥基、-(CrCd烷基、_(c3_ c7)環烷基、-(c2-c9)雜環基、-cKCrCd烷基、-〇(C3_c7) 環烷基、-〇(C2-C9)雜環基、-NR5R6、-SR7、-SOR7、 - S02R7、一 C〇2R!2、_c〇nr5r6、一 s〇2Nr5r6、一 nhc〇r12、 - nr12conr5r6、和-NR12S02R7之取代基；其中該R1取代棊 • 之-(Crc6)烷基、-(c3-c7)環烷基、-(C2-C9)雜環基、 烷基、-〇(c3-c7)環烷基、-0(c2-c9)雜環基、 - NR5R6、_SR7、一 s〇R7、一 s〇2r7、_c〇2r12、一 c〇nr5r6、 - S〇2NR5R6、_NHC〇Rl2、一 NRl2C〇NR5R6、和一 NRl2S〇2R7_ 任意地經1至3個分別選自氫、鹵素、羥基、-CF3、、cN 、-(C^Ce)院基、-NR5R6、-OR12、-(C3-C7)環烷基、 一（C2-C9)雜環基、一C〇2R12、一C〇NR5r6、和一c〇NR5R8;^_ 團所取代； 各個R2是分別選自氫、-(C〗_C6)烷基、-(C2-C6)烯基 、一（C2-C6)炔基、-(c3-c7)環院基、-(C2-C9)雜環基、 -197- 200539871 (2) -C02R12、和-CONR5R6之取代基；其中該R2取代基之-(Ci-C6)烷基、-(C2-C6)烯基、-（C2_C6)炔基、-(c3-c7)環烷基 、-(C2-C9)雜環基、-C02R12、和-conr5r6任意地經上至；^ 個分別選自氫、鹵素、羥基、-CF3、-N02、-CN、-(C「 C6)烷基、-(C2-C6)烯基、-(C2-C6)炔基、-ON-OH、 一 C = N - OUCrCj 焼基）、_NR5R6、一OR"、_(C3 —C7)環烷基 、-(C2-C9)雜環基、_C02R12、- CONR5R6、-CONR5R8、 •-SR7、一 SOR7、-S02R7、- S02NR5R6、-NHCOR12、 - NR12CONR5R6、和-NR12S02R7之基團所取代，其中該R2基 團之-(c2-c6)烯基和-(c2-c6)炔基可任意地經1至3個R12基 團所取代； R1和R2可與相連接的原子一起形成-(C3-C1())環烷基 或一（C2-C9)雜環基之環狀基團，其中該環狀基團任意地經 1至3個分別選自氫、鹵素、羥基、—Cf3、-n〇2、— CN、 一（crC6)院基、一（c2-C6)嫌基、-（C2-C6)炔基、-C = N- 〇H •、一C = N —◦((CrCj 院基）、一NR5R6、一〇R12、一（C3-C7)環院 基、-（C2-C9)雜環基、_C〇2R12、-CONR5R6、-c〇NR5R8 、-SR?、一S〇R7、一S02R7、一S〇2NR5R6、一NHC0R12、 _nr12c〇Nr5r6、和一NRl2s〇2R7之基團所取代，其中該環狀 基團之-（C2 —C6)烯基和-(c2-c6)炔基可任意地經1至3個R12 $ Η所取代，及該環狀基團任意地爲1至3個選自—（c = 〇) 、-s〇2、一s一、一〇一、一N_、_NH_和一NR"之單元所中斷； R3M選自下列之取代基： (a)氫； -198 - 200539871 (3) (b) -(C6-C1())芳基或-(cvcd雜芳基，而其任意地經1 至3個分別選自鹵素、羥基、-(CrC 6)烷基、-(C^C 6)烷 基-P (Ο ) (Ο (C 丨-C 6)院基）2、- (C 3 - C 丨。）環院基、-(c 6 - C 】。）芳 基、-(c2-c9)雜環基、-(CrCj雜芳基、-nr5r6、 - NHSCMCi-Ce)烷基、-NHS02(C3-C6)環烷基、-md-Ce) 烷基 MSCMC^-CJ烷基）、-NUCi-Ce)烷基）（S02(C3-C6)環烷 基）、-N((C3-C6)環烷基 MSO^Ci-Ce)烷基）、-N((C3-C6)環 院基）（S02(C3-C6)環院基）、-OiC〗-C6)院基、-O-SOzCCj-c6)烷基、-〇-S02(C3-C6)環烷基、-(COMCi-Ce)烷基、 -（CO)CF3、-（CO)(C3_C10)環院基、-(c〇)(C6-C10)芳基、 -（co)(c2-c9)雜環基、-（COKCrCg)雜芳基、-(CCOCKCr C6)院基、-(C0)0(C3-C1())環院基、-(c〇)0(C6-C1())芳基 、-（C0)0(C2-C9)雜環基、-(CCOOiCi-Cg)雜芳基、 -(COKC^Cd 烷基-CXC^Ce)烷基-、-SCMC^Cd烷基、 -S02(c3-c6)環烷基、-S02CF3、-S02NH2、-SC^NHiCi-Ce) ® 烷基、-S02NH(C3-C6)環烷基、-SC^NUCrCe)烷基）2、 -SC^NUC】-C6)烷基）（（C3-C6)環烷基）、-s〇2N((C3-C6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-(C6-Cl。）芳基 或-（C^-Cg)雜芳基任意地爲1至3個選自-S-、-0-、-N-、 -NH-和-NR12之單元所中斷； (c) -(C3-C1())環烷基、-(C2-C9)雜環基、和-(C^-Ce)烷 基-(C2-C9)雜環基，而其任意地經1至3個分別選自鹵素、 羥基、-(CrCj 烷基、-（CrC6)烷基-PiOMcKC^Ce)烷基）2 、-(C3-C1())環烷基、-(C6-C1())芳基、-(C2-C9)雜環基、 •199- 200539871 (4) -(C^-CJ雜芳基、_NR5R6、-NHSO^CrCe)烷基、 -NHS〇2(C3-C6)環烷基、-NUCrCd 烷基）（S02(C】_C6)烷基） 、-NUCi-Cd 烷基）（S02(C3-C6)環烷基）、-N((C3-C6)環烷 基 KSO^C^-Ce)烷基）、-N((C3-C6)環烷基）（S02(C3_C6)環烷 基）、一院基、-O-SO^C^-Ce)院基、-〇-S02(C3-C6)環烷基、-(COMCrCj烷基、_(C0)CF3、-(C0)(C3-C10)環烷基、-（co)(c6-cI(>)芳基、-(co)(c2-c9)雜環基 、-(COMC^-Cd雜芳基、-（CCOCHC^-Ce)烷基、 -（co)o(c3-c10)環烷基、-(co)o(c6-c10)芳基、 -(co)o(c2-c9)雜環基、-(CCOCKC^CP雜芳基、 -（00)((：1-(：6)烷基-〇（(：1-(：6)烷基-、-502((：1-0：6)烷基、 -so2(c3-c6)環烷基、-so2cf3、-so2nh2、-so2nh(c「c6) 烷基、-S02NH(C3-C6)環烷基、-SC^NUC^-Ce)烷基）2、 -SC^NGC^-Ce)烷基）（（C「C6)環烷基）、-5 02以（(：3-(：6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-(c3-c1())環烷 基、-(c2-c9)雜環基、和-(Ci-cj烷基-(c2-c9)雜環基任 意地爲 1至 3個選自-(C = 0)、-S02、-s-、-ο -、-N-、 - NH -和-NR12之單兀所中斷； (¢3)-((^-(^)烷基，而其任意地經1至3個分別選自鹵素 、羥基、-（(^-0：6)烷基、-（C^-Ce)烷基-PiOKCKCrCe)烷 基）2、-(c3-c1())環烷基、-(C6-C1D)芳基、-(C2_C9)雜環基 、-（C】-C9)雜芳基、-NR5R6、-NHSCMCi-Cj 烷基、 - NHS02(C3-C6)環烷基、-NUCi-Cj 烷基 MSOjC^Ce)烷基） 、-NKC^-Ce)烷基）（S02(C3-C6)環烷基）、-N((C3-C6)環烷 -200- 200539871 ⑸ 基 HSCMC^-Cd烷基）、-n((c3-c6)環烷基）（so2(c3-c6)環烷 基）、_〇（（：「C6)烷基、-〇-S 0 2((^-06)烷基、-〇- so2(c3 -c6)環烷基、-（COKC^Ce)烷基、-(CO)CF3、_(CO)(C3-C10)環烷基、-(c〇）（c6-c10)芳基、-(co)(c2-c9)雜環基 、-（COHCrCj 雜芳基、-（CCOCKCrCe)烷基、 -（co)o(c3-c1())環烷基、-(co)o(c6-c1(})芳基、 -（co)o(c2-c9)雜環基、-(CCOOd-Cg)雜芳基、 _ -(匸〇）（(3「〇6)院基-〇（01-06)院基-、-502(01-06)焼基、 -so2(c3-c6)環烷基、-so2cf3、-so2nh2、-so2nh(c「c6) 院基、-S02NH(C3-C6)環院基、-sOgNGCrCe)垸基）2、 - SC^NHC^-Ce)烷基）（（c3-c6)環烷基）、-S〇2N((c3-c6)環烷 基）2、和-S02NR5R6之基團所取代，其中該_(Cl-c6)烷基任 意地爲1至3個選自-(C = 0)、〜S〇2、-S-、-0-、-N-、 -NH-和-NR12之單元所中斷； 及其中各個R3之（b)-(d)取代基、基團或單元任意地經 • 1至3個分別選自氫、鹵素、羥基、—CF3、-N02、-CN、 -(C^Ce)烷基、-（C2_C6)烯基、-(c2 - C6)炔基、-（C3-C7)環 烷基、-(C2-C9)雜環基、-(C6-C1())芳基、-(c「c9)雜芳基 、-CKCrCd烷基、-0(c3-c7)環烷基、-〇（c2-C9)雜環基 、一C = N-〇H、_C = N_〇（（C「C6)烷基）、一NR5R6、_SR7、 一S〇R7、一S〇2R7、一c〇2r12、〜c〇nr5r6、一s〇2nr5r6、 -NHCOR5、-NR12CONR5R6、和-NR12S〇2R7之基圑所取代； R4是選自氫、烷基、-(c3_c7)環烷基和-(〇2-c9)雜環基之取代基；其中該R4取代基之-(Cl-C6)烷基、 -201 - 200539871 (6) -（c3-c7)環烷基和- (C^C9)雜環基任意地經1至3個分別選 自氫、鹵素、羥基、—（Ci — C6)烷基、-CN、-NR5R6、_〇R5 、-（c3-c7)環烷基、-(c2-c9)雜環基、-c〇2r12、 -S02NR5R6、，R12S02K7、〜S〇2r7、和-conr5r8 之基團所 取代；其中該- CONR5R8中之R4(]R8可與相連結的原子一 起形成-(C2-C9)雜環基； R5和R6各是分別選自氫、〜（CrC6)烷基' -(C3-(：7)環 Φ烷基——（C2-。9)雜環基、-(CrC!。）芳基、-(CrCg)雜芳基 、-COR12、和- S02R12之取代基；其中該和R6取托基之 -（(^-(：6)烷基、_(C3-C7)環烷基、—（c2-C9)雜環基、-（C6-Ci。）芳基、-(C^-Cg)雜芳基、-COR12、和-S02R】2任意地經 1至3個分別選自氫、鹵素、-CF3、-CN、-(C】-C6)院基、 -ΝΗ((^-ί：6)烷基、-NH(C3-C7)環烷基、_nh(C2 —C9)雜環基 、-NH(C6-C1())芳基、-NH(C「C9)雜芳基、—N((Ci —c6)烷基 )2、-N((c3-c7)環烷基）2、-N((C2-C9)雜環基）2、-N((c6-C")方基）2、- NGC^-Cg)雜方基）2、-院基、 -〇（c3 - C7)環院基、-0(c2-c9)雜環基、-〇(c「C10)芳基、 -〇（(：「C9)雜芳基、-(C3-C7)環烷基、-(c2-C9)雜環基、 一 C〇2R7、一S〇2NR5R6、一NR12s〇2R7、一s〇2r7、一c〇nh2、 -CONHR7、和-CONR7R8之基團所取代；其中該-c〇NR7R8 中之R7和R8可與相連結的氮原子一起形成- (C2-C9)雜環基 R5和R6可與相連結的原子一起形成-(C2_C9)雜環基， 其中該_(C2-C9)雜環基任意地經1至3個分別選自氫、鹵素 -202· 200539871 (7) 、羥基、-CF3、-N〇2、-CN、-（C】-C6)院基一（C2-C6m 基、一（C2~C6)'炔基、~C = N-〇H、一C = N-院基）、 _nr7r8、'〇R12、-(c3-c7)環烷基、-(C2-C9)雜環基、φ or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof, wherein η is an integer from 1 to 3; each R1 is selected from hydrogen, hydroxyl,-(CrCd alkyl, _ (c3_c7) ring Alkyl,-(c2-c9) heterocyclyl, -cKCrCd alkyl, -〇 (C3-C7) cycloalkyl, -〇 (C2-C9) heterocyclyl, -NR5R6, -SR7, -SOR7,-S02R7, A C02R! 2, _c〇nr5r6, a so2Nr5r6, a nhcor12, -nr12conr5r6, and -NR12S02R7 substituents; wherein R1 replaces-(Crc6) alkyl,-(c3-c7 ) Cycloalkyl,-(C2-C9) heterocyclyl, alkyl, -〇 (c3-c7) cycloalkyl, -0 (c2-c9) heterocyclyl, -NR5R6, -SR7, -sOR7, -S02r7, _c〇2r12, -cnr5r6,-S〇2NR5R6, -NHC〇Rl2, -NR12C0NR5R6, and -NRl2S〇2R7_ are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl,- CF3 ,, cN,-(C ^ Ce) courtyard, -NR5R6, -OR12,-(C3-C7) cycloalkyl, one (C2-C9) heterocyclyl, one C02R12, one CONR5r6, And a co-NR5R8; ^ _ group; each R2 is selected from hydrogen,-(C〗 _C6) alkyl,-(C2-C6) alkenyl, mono (C2-C6) alkynyl,- (c3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -197- 200539871 (2) -C02R12, and -CONR5R6 substituents; wherein-(Ci-C6) alkyl of the R2 substituent ,-(C2-C6) alkenyl,-(C2-C6) alkynyl,-(c3-c7) cycloalkyl,-(C2-C9) heterocyclyl, -C02R12, and -conr5r6 arbitrarily go up; ^ Each selected from hydrogen, halogen, hydroxyl, -CF3, -N02, -CN,-(C "C6) alkyl,-(C2-C6) alkenyl,-(C2-C6) alkynyl, -ON-OH , One C = N-OUCrCj fluorenyl), _NR5R6, one OR ", _ (C3-C7) cycloalkyl,-(C2-C9) heterocyclyl, _C02R12,-CONR5R6, -CONR5R8, • -SR7, one SOR7, -S02R7, -S02NR5R6, -NHCOR12, -NR12CONR5R6, and -NR12S02R7 are substituted with the-(c2-c6) alkenyl and-(c2-c6) alkynyl groups of the R2 group 1 to 3 R12 groups are substituted; R1 and R2 may form a-(C3-C1 ()) cycloalkyl or a (C2-C9) heterocyclyl cyclic group together with the connected atoms, where the The cyclic group is arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, -Cf3, -n〇2, -CN, a (crC6) courtyard group, a (c2-C6) alkyl group, and-(C2 -C6) alkynyl, -C = N -〇H •, one C = N —◦ ((CrCj courtyard), one NR5R6, one 〇R12, one (C3-C7) ring courtyard,-(C2-C9) heterocyclic group, _C〇2R12,- CONR5R6, -coNR5R8, -SR ?, -SOR7, -S02R7, -SO2NR5R6, -NHCOR12, (C2-C6) alkenyl and-(c2-c6) alkynyl may be optionally substituted with 1 to 3 R12 $ Η, and the cyclic group is arbitrarily selected from 1 to 3 selected from-(c = 〇 ), -S〇2, -s-1, -101, -N_, _NH_ and -NR " are interrupted; R3M is selected from the following substituents: (a) hydrogen; -198-200539871 (3) ( b)-(C6-C1 ()) aryl or-(cvcdheteroaryl), which are arbitrarily selected from 1 to 3, respectively, selected from halogen, hydroxyl,-(CrC 6) alkyl,-(C ^ C 6 ) Alkyl-P (0) (0 (C 丨 -C 6) based) 2,-(C 3-C 丨. ) Cyclocyclyl,-(c 6-C).) Aryl,-(c2-c9) heterocyclyl,-(CrCj heteroaryl, -nr5r6, -NHSCMCi-Ce) alkyl, -NHS02 (C3- C6) cycloalkyl, -md-Ce) alkyl MSCMC ^ -CJ alkyl), -NUCi-Ce) alkyl) (S02 (C3-C6) cycloalkyl), -N ((C3-C6) ring Alkyl MSO ^ Ci-Ce) alkyl), -N ((C3-C6) ring courtyard) (S02 (C3-C6) ring courtyard), -OiC〗 -C6) courtyard, -O-SOzCCj- c6) alkyl group, -0-S02 (C3-C6) cycloalkyl group,-(COMCi-Ce) alkyl group,-(CO) CF3,-(CO) (C3-C10) cyclocopheryl group,-(c〇) ( C6-C10) aryl group,-(co) (c2-c9) heterocyclyl group,-(COKCrCg) heteroaryl group,-(CCOCKCr C6) group,-(C0) 0 (C3-C1 ()) ring group ,-(C0) 0 (C6-C1 ()) aryl,-(C0) 0 (C2-C9) heterocyclyl,-(CCOOiCi-Cg) heteroaryl,-(COKC ^ Cd alkyl- CXC ^ Ce) alkyl-, -SCMC ^ Cd alkyl, -S02 (c3-c6) cycloalkyl, -S02CF3, -S02NH2, -SC ^ NHiCi-Ce) ® alkyl, -S02NH (C3-C6) Cycloalkyl, -SC ^ NUCrCe) alkyl) 2, -SC ^ NUC] -C6) alkyl) ((C3-C6) cycloalkyl), -s〇2N ((C3-C6) cycloalkyl) 2, and -so2nr5r6 are substituted, wherein the-(C6-Cl.) Aryl or-(C ^ -Cg) heteroaryl is optionally Interrupted by 1 to 3 units selected from -S-, -0-, -N-, -NH- and -NR12; (c)-(C3-C1 ()) cycloalkyl,-(C2-C9) Heterocyclyl, and-(C ^ -Ce) alkyl- (C2-C9) heterocyclyl, which are optionally selected from 1 to 3, respectively, selected from halogen, hydroxyl,-(CrCj alkyl,-(CrC6) Alkyl-PiOMcKC ^ Ce) alkyl) 2,-(C3-C1 ()) cycloalkyl,-(C6-C1 ()) aryl,-(C2-C9) heterocyclyl, -199- 200539871 ( 4)-(C ^ -CJ heteroaryl, _NR5R6, -NHSO ^ CrCe) alkyl, -NHS〇2 (C3-C6) cycloalkyl, -NUCrCd alkyl) (S02 (C) _C6) alkyl) , -NUCi-Cd alkyl) (S02 (C3-C6) cycloalkyl), -N ((C3-C6) cycloalkylKSO ^ C ^ -Ce) alkyl), -N ((C3-C6) (Cycloalkyl) (S02 (C3_C6) cycloalkyl), one courtyard, -O-SO ^ C ^ -Ce) courtyard, -0-S02 (C3-C6) cycloalkyl,-(COMCrCj alkyl, _ (C0) CF3,-(C0) (C3-C10) cycloalkyl,-(co) (c6-cI (>) aryl,-(co) (c2-c9) heterocyclyl,-(COMC ^ -Cd heteroaryl,-(CCOCHC ^ -Ce) alkyl,-(co) o (c3-c10) cycloalkyl,-(co) o (c6-c10) aryl,-(co) o ( c2-c9) heterocyclyl,-(CCOCKC ^ CPheteroaryl,-(00) ((: 1-(: 6) alkyl-0 ((: 1-(: 6) alkyl-, -502 ( (:1- 0: 6) alkyl, -so2 (c3-c6) cycloalkyl, -so2cf3, -so2nh2, -so2nh (c "c6) alkyl, -S02NH (C3-C6) cycloalkyl, -SC ^ NUC ^ -Ce) alkyl) 2, -SC ^ NGC ^ -Ce) alkyl) ((C "C6) cycloalkyl), -502 to ((: 3-(: 6) cycloalkyl) 2, and -so2nr5r6 is substituted with any of the-(c3-c1 ()) cycloalkyl,-(c2-c9) heterocyclyl, and-(Ci-cjalkyl- (c2-c9) heterocyclyl Ground is interrupted by 1 to 3 units selected from-(C = 0), -S02, -s-, -ο-, -N-, -NH-and -NR12; (¢ 3)-((^ -(^) Alkyl, which is arbitrarily selected from 1 to 3 selected from halogen, hydroxyl,-((^-0: 6) alkyl,-(C ^ -Ce) alkyl-PiOKCKCrCe) alkyl) 2,-(c3-c1 ()) cycloalkyl,-(C6-C1D) aryl,-(C2-C9) heterocyclyl,-(C) -C9) heteroaryl, -NR5R6, -NHSCMCi-Cj alkane -NHS02 (C3-C6) cycloalkyl, -NUCi-Cj alkyl (MSOjC ^ Ce) alkyl), -NKC ^ -Ce) alkyl) (S02 (C3-C6) cycloalkyl), -N ((C3-C6) cycloalkane-200- 200539871 fluorenyl HSCMC ^ -Cd alkyl), -n ((c3-c6) cycloalkyl) (so2 (c3-c6) cycloalkyl), _〇 (( : "C6) alkyl, -0-S 0 2 ((^-06) alkyl, -〇- so2 ( c3 -c6) cycloalkyl,-(COKC ^ Ce) alkyl,-(CO) CF3, _ (CO) (C3-C10) cycloalkyl,-(c〇) (c6-c10) aryl,- (co) (c2-c9) heterocyclyl,-(COHCrCj heteroaryl,-(CCOCKCrCe) alkyl,-(co) o (c3-c1 ()) cycloalkyl,-(co) o (c6- c1 (}) aryl,-(co) o (c2-c9) heterocyclyl,-(CCOOd-Cg) heteroaryl, _-(匸 〇) ((3 「〇6) 院 基 -〇 (01 -06) Yuanji-, -502 (01-06) fluorenyl, -so2 (c3-c6) cycloalkyl, -so2cf3, -so2nh2, -so2nh (c 「c6) Yuanji, -S02NH (C3-C6 ) Cyclosyl, -sOgNGCrCe) fluorenyl) 2, -SC ^ NHC ^ -Ce) alkyl) ((c3-c6) cycloalkyl), -S〇2N ((c3-c6) cycloalkyl) 2 , And -S02NR5R6, wherein the _ (Cl-c6) alkyl group is arbitrarily selected from 1 to 3 selected from-(C = 0), ~ S〇2, -S-, -0-,- The units of N-, -NH- and -NR12 are interrupted; and (b)-(d) substituents, groups or units of each R3 are arbitrarily selected from 1 to 3 selected from hydrogen, halogen, hydroxyl, --CF3, -N02, -CN,-(C ^ Ce) alkyl,-(C2-C6) alkenyl,-(c2-C6) alkynyl,-(C3-C7) cycloalkyl,-(C2-C9) Heterocyclyl,-(C6-C1 ()) aryl,-(c "c9) heteroaryl, -CKCrCd alkyl, -0 (c3-c7) cycloalkyl, -〇 (c2-C9) heterocyclyl, -C = N-OH, -C = N_〇 ((C "C6) alkyl), -NR5R6, _SR7, -SOR7, -SO2R7, -co2r12, ~ connr5r6, -so2nr5r6, -NHCOR5, -NR12CONR5R6, and -NR12S〇2R7 are replaced by the base; R4 is optional Substituents for hydrogen, alkyl,-(c3_c7) cycloalkyl and-(〇2-c9) heterocyclyl; wherein-(Cl-C6) alkyl of the R4 substituent, -201-200539871 (6) -(C3-c7) cycloalkyl and-(C ^ C9) heterocyclyl are optionally selected from hydrogen, halogen, hydroxyl,-(Ci-C6) alkyl, -CN, -NR5R6, _〇R5,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl, -co2r12, -S02NR5R6 ,, R12S02K7, ~ S〇2r7, and -conr5r8; R4 (] R8 in the -CONR5R8 may form a-(C2-C9) heterocyclyl together with the linked atoms; R5 and R6 are each selected from hydrogen, ~ (CrC6) alkyl '-(C3- (: 7) CycloΦalkyl-(C2-. 9) Heterocyclyl,-(CrC!.) Aryl,-(CrCg) heteroaryl, -COR12, and -S02R12 substituents; where and R6 take-((^-(: 6) Alkyl, _ (C3-C7) cycloalkyl,-(c2-C9) heterocyclyl,-(C6-Ci.) Aryl,-(C ^ -Cg) heteroaryl, -COR12, and -S02R ] 2 arbitrarily selected from 1 to 3 selected from hydrogen, halogen, -CF3, -CN,-(C) -C6), radical, -NΗ ((^-ί: 6) alkyl, -NH (C3- C7) cycloalkyl, _nh (C2-C9) heterocyclyl, -NH (C6-C1 ()) aryl, -NH (C 「C9) heteroaryl, -N ((Ci -c6) alkyl) 2, -N ((c3-c7) cycloalkyl) 2, -N ((C2-C9) heterocyclyl) 2, -N ((c6-C ") square group) 2, -NGC ^ -Cg) Heterocyclyl) 2, -Chenyl, -〇 (c3-C7) ring, Cyanyl, -0 (c2-c9) heterocyclyl, -〇 (c "C10) aryl, -〇 ((:" C9) Heteroaryl,-(C3-C7) cycloalkyl,-(c2-C9) heterocyclyl, -C02R7, -S02NR5R6, -NR12s〇2R7, -s02r7, -conh2,- CONHR7, and -CONR7R8 are substituted; wherein R7 and R8 in -co-NR7R8 can be formed with a nitrogen atom that is linked-(C2-C9) heterocyclyl R5 and R6 can be together with a linked atom Formation-(C2_C9) Group, wherein the _ (C2-C9) heterocyclyl group is optionally selected from hydrogen, halogen-202 · 200539871 (7), hydroxyl group, -CF3, -N02, -CN,-(C 】 -C6) Yuan Jiyi (C2-C6m group, Yiyi (C2 ~ C6) 'alkynyl group, ~ C = N-〇H, -C = N-〇HY), _nr7r8,' 〇R12,-(c3- c7) cycloalkyl,-(C2-C9) heterocyclyl, 一 C〇2R12、 一C〇NR7R8、 -CONR5R8 ' -SR7 > 一S〇R7、 -S02R7 、-S02NR7rs , -NHCOR12 > -NR12CONR7R8 ^ ^D-NR12S02R7 之基團所取代，其中該-（C2-C9)雜環基之-(C2-C6)烯基和 -（CfC6)炔基可任意地經1至3個1^7基所取代，及該—（C2_ C9)雜環基任意地爲1至3個選自_(c = 〇)、—s〇2、-s—、-〇_ 、-N-、和_NR12之單元所中斷； R7是選自-(CrCj烷基、-(C3-C7)環烷基、-(C2-C9) 雜環基、-(c6-c1D)芳基、和-(CrCj雜芳基之取代基；其 中該R7取代基之烷基、_(C3-C7)環烷基、-(c2-c9) 雜環基、-（C6-C1Q)芳基、和-(q-Cj雜芳基任意地經1至3 個分別選自氫、鹵素、羥基、-CN、-(C^-Ce)烷基、 - NR122、和-〇(C】一 c6)院基之基團所取代； R8是選自氫、-(CrCe)烷基、-(c3-c7)環烷基、-（c2-c9)雜環基、-(C6-C1())芳基、和-（CrCd雜芳基之取代基 ;其中該R8取代基之-（CrCe)烷基、-(c3-c7)環烷基、 -（c2-c9)雜環基、-(c6-C1())芳基、和- (CrCg)雜芳基任意 地經1至3個分別選自氫、鹵素、羥基、-CN、-((^-(^烷 基、-NH2、-NHR9、-NR92、_〇R9、-（C「C7)環烷基、 一（C2_C9)雜環基、一C〇2R10、一C0NH2、一CONHR10、禾口 -CONRMR11之基團所取代；其中該-CONRWR11中之R1Q和 R11可與相連結的氮原子一起形成_(C2_C9)雜環基； -203- 200539871 (8) R9和R1()分別各是-(Cl-C6)烷基； R"是氫或-(C^c6)烷基；及 R12是選自氫、-（Cl-c6)烷基、-(c3-c7)環烷基、 -(c2-c9)雜環基、-（C6-Ci。）芳基、和_(Ci —C9)雜芳基之取 代基；其中該R12取代基之_((：1-(：6)烷基、-(c3-c7)環烷基 、-（C2-C9)雜環基、一（c6-CiD)芳基、和-(Ci-C9)雜芳基任 意地經1至3個分別選自氫、鹵素、-CF3、-CN、-(CrCe) 修烷基、-NHd-Cd烷基、-Nh(C「C7)環烷基、-NH(C2-C9) 雜環基、-NH(C6-C1())芳基、雜芳基、-N((Cr C6)烷基）2、-N((C3-C7)環烷基）2、-N((C2-C9)雜環基）2、 - N((C6-C1())芳基）2、-N((c「c9)雜芳基）2、-〇(Cl-C6)烷基 、-〇(C3-C7)環烷基、-〇(c2-C9)雜環基、-o(c6-c1())芳基 、-〇(〇:!-c9)雜芳基、-(C3-C7)環烷基、-(c2-c9)雜環基 、一 C〇2R7、一c〇NH2、一CONHR7、禾口 -CONR7R8之基團所取 代；其中該-CONR7R8中之R7和R8可與相連結的原子一起 •形成-(c2一C9)雜環基。 2·如申請專利範圍第1項之化合物，其中R3是氫。 3·如申請專利範圍第1項之化合物，其中R3是選自 -（C6_C1())芳基或-(C「C9)雜芳基，而其任意地經1至3個分 別選自鹵素、羥基、-(C^CJ烷基、-(CrCd烷基一 Ρ(〇）（〇（^-(^6)院基）2、-(C3-C1())環院基、-(CrC!。）方基 、-（C2-C9)雜環基、-(CrCg)雜芳基、-nr5r6、 -NHSO^Ci-Cd 烷基、-NHS02(C3-C6)環烷基、-NUCrCj 烷基 KSOJCrCe)烷基）、_N((CrC6)烷基）（S02(C3-C6)環烷 •204 - 200539871 (9) 基）、-N((C3_C6)環烷基 MSOjCrCe)烷基）、-N((c3-c6)環 烷基）（s〇2(c3-c6)環烷基）、-〇（C「C6)烷基、-0-s〇2(c】-c6)烷基、-o-so2(c3-c6)環烷基、-(COMCrCj烷基、 -（CO)CF3、-（c〇）（c3-c10)環烷基、-(CO)(C6-C10)芳基、 -（CO)(C2-C9)雜環基、-(COMCrCP 雜芳基、-(CO)O(Cr c6)烷基、_(co)o(c3-c1())環烷基、-(cc^cHCrG。）芳基 、-（co)o(c2-c9)雜環基、-(C〇)〇(Cl-C9)雜芳基、 籲-（CO)(C〗-C6)烷基-Od-Ce)烷基-、-SOjCi-C6)烷基、 -S02(c3-c6)環烷基、-S〇2CF3、-S02NH2、-SOjjNHiC^Ce) 烷基、-so2nh(c3-c6)環烷基、-so2N((c】-c6)烷基）2、 - SOaNGC^-Ce)院基）（（C3-C6)環院基）、-S02N((C3-C6)環院 基）2、和-S02NR5R6之基團所取代，其中該-(c6-C1Q)芳基 或—⑷广c9)雜芳基任意地爲1至3個選自-S-、-0-、-N-、 -NH-和-NR12之單元所中斷。 4·如申請專利範圍第1項之化合物，其中R3是選自 ® -(c3-c1())環烷基、-(C2-C9)雜環基、和-(Cl —c6)烷基-(c2 — C9)雜環基，而其任意地經丨至3個分別選自鹵素、羥基、 -（CrCJ 烷基、-(Ci-c6)烷基-PaKCKCrCe)烷基）2、 -（C3-c1())環烷基、—（C6-Ci。）芳基、—（c2_c9)雜環基、 -（C〗-C9)雜芳基、-NR5R6、-NHSCMC〗-c6)烷基、 -nhso2(c3-c6)環烷基、-N((C「C6)烷基 HSOjCrCe)烷基） 、-N((c 丨-c6)烷基）（S02(C3-C6)環烷基）、-N((c3-c6)環烷 基）（5〇2(<31-(：6)烷基）、-1^((〇3-0：6)環烷基）（5〇2((：3-0：6)環烷 基）、-〇（C「C6)烷基、-O-SOjCrCe)烷基、-〇-s〇2(c3- -205- 200539871 (10) c6)環烷基、-（c〇）（c「c6)烷基、-(c〇）cf3、-(c〇）（c3-C10)環烷基、-（c〇）（c6-c】。）芳基、-(co)(c2-c9)雜環基 、-（CO)(C「C9)雜芳基、-(CC^CKCrCe)烷基、 -（co)o(c3-c1Q)環烷基、-(C0)0(C6-C1())芳基、 -(co)o(c2-c9)雜環基、-(CCOCHC^Cd雜芳基、 -(CO)(C「C6)烷基-〇（C「C6)烷基-、-SCMC^-Ce)烷基、 一 S〇2(C3 - C6)環垸基、一S〇2CF3、一 S〇2NH2、一SC^NhUC^Ce) •烷基、-S02NH(C3-C6)環烷基、-SC^NGCrCe)烷基）2、 -SC^NUC^-Ce)烷基）（（C3_C6)環烷基）、-S02N((C3-C6)環烷 基）2、和-so2nr5r6之基團所取代，其中該-(c3-c1())環烷 基、-(C2-C9)雜環基、和-(CrCj烷基-(c2-c9)雜環基任 意地爲 1至 3個選自-（C = 0)、-S〇2、-S -、-〇-、-N-、 -NH-和-NR12之單元所中斷。 5.如申請專利範圍第1項之化合物，其中R3是-(C^-Ce) 烷基’而其任意地經1至3個分別選自鹵素、羥基、-（Cr • C6)烷基、-(CrCj 烷基-PiOHCHC^-Ce)烷基）2、_(C3 - C10) 環烷基、-(c6-c1())芳基、-(C2-C9)雜環基、-(Crc9)雜芳 基、-NR5R6、一NHS〇2(C「C6)烷基、-NHS〇2(C3-C6)環烷基 、-烷基 KSOjCrCd 烷基）、-NGC^-Ce)烷基 )(S〇2(C「C6)環烷基）、-N((C3-C6)環烷基）（S02(C「C6)烷基 )、-n((c3-c6)環烷基）（so2(c3-c6)環烷基）、-0(0】-(：6)烷 基、-0-s〇2(c「c6)烷基、-0-S02(c3-c6)環烷基、 -(COMCrc6)烷基、-(co)cf3、-（co)(c3-c1())環烷基、 -（C0)(c6-Cl。）芳基、_(CO)(C2-C9)雜環基、-(COMC^-C,) -206- 200539871 (11) 雜芳基、-(CC^CHCrCe)烷基、-（C〇）0(C3-C1())環烷基、 -((：〇）〇（(：6-(：1。）芳基、-((：〇)〇（0：2-(：9)雜環基、 -（CCOCMCrCg)雜芳基、-（C〇）（C「C6)烷基-CHCrCe)烷 基-、-SO^CrCe)烷基、-S〇2(c3-c6)環烷基、-S〇2CF3 、—s〇2nh2、-s〇2nh(c「c6)烷基、-s〇2nh(c3-c6)環烷基 、-S〇2N((CrC6)烷基）2、-S〇2N((C「C6)烷基）（（C3 - C6)環 烷基）、-S〇2N((C3 - c6)環烷基）2、和-so2nr5r6之基團所取 # 代，其中該-(C「C6)烷基任意地爲1至3個選自-(c = 〇）、 -S〇2、-s-、- N-、-NH -和-NR12 之單元所中斷。 6 ·如申請專利範圍第i至5項中任一項之化合物，其係 如下式2所示：-CO2R12, -CONR7R8, -CONR5R8 '-SR7 > -SOR7, -S02R7, -S02NR7rs, -NHCOR12 > -NR12CONR7R8 ^^ D-NR12S02R7 are replaced by the group, in which-(C2 -C9) heterocyclyl- (C2-C6) alkenyl and-(CfC6) alkynyl may be optionally substituted with 1 to 3 1 ^ 7 groups, and the-(C2_C9) heterocyclyl is arbitrarily 1 to 3 units selected from _ (c = 0), -s〇2, -s-, -〇_, -N-, and _NR12 are interrupted; R7 is selected from-(CrCj alkyl,-( C3-C7) cycloalkyl,-(C2-C9) heterocyclyl,-(c6-c1D) aryl, and-(CrCj heteroaryl substituents; wherein the alkyl group of the R7 substituent, _ (C3 -C7) cycloalkyl,-(c2-c9) heterocyclyl,-(C6-C1Q) aryl, and-(q-Cj heteroaryl are optionally selected from hydrogen, halogen, and hydroxyl , -CN,-(C ^ -Ce) alkyl, -NR122, and -0 (C) -c6) are substituted by radical groups; R8 is selected from hydrogen,-(CrCe) alkyl,-(c3 -c7) cycloalkyl,-(c2-c9) heterocyclyl,-(C6-C1 ()) aryl, and-(CrCd heteroaryl substituents; wherein the R8 substituent is-(CrCe) alkane ,-(C3-c7) cycloalkyl,-(c2-c9) heterocyclyl,-(c6-C1 ()) aryl, and-(CrCg ) Heteroaryl is optionally selected from 1 to 3 by hydrogen, halogen, hydroxyl, -CN,-((^-(^ alkyl, -NH2, -NHR9, -NR92, -〇R9,-(C " C7) a cycloalkyl group, a (C2_C9) heterocyclyl group, a CO2R10, a COH2, a CONHR10, and a -CONRMR11 group; wherein R1Q and R11 in -CONRWR11 may be bonded to the nitrogen The atoms together form a _ (C2_C9) heterocyclic group; -203- 200539871 (8) R9 and R1 () are each-(Cl-C6) alkyl; R " is hydrogen or-(C ^ c6) alkyl; and R12 is selected from hydrogen,-(Cl-c6) alkyl,-(c3-c7) cycloalkyl,-(c2-c9) heterocyclyl,-(C6-Ci.) Aryl, and _ (Ci — C9) a heteroaryl substituent; wherein-((: 1-(: 6) alkyl,-(c3-c7) cycloalkyl,-(C2-C9) heterocyclyl,-( c6-CiD) aryl, and-(Ci-C9) heteroaryl are optionally selected from 1 to 3, respectively, selected from hydrogen, halogen, -CF3, -CN,-(CrCe) alkylene, -NHd-Cd alkane , -Nh (C "C7) cycloalkyl, -NH (C2-C9) heterocyclyl, -NH (C6-C1 ()) aryl, heteroaryl, -N ((Cr C6) alkyl) 2, -N ((C3-C7) cycloalkyl) 2, -N ((C2-C9) heterocyclyl) 2,-N ((C6-C1 ()) aryl) 2, -N ((c c9) heteroaryl) 2, -〇 (Cl-C6) alkyl, -〇 (C3-C7) cycloalkyl, -〇 (c2-C9) heterocyclyl, -o (c6-c1 ()) aryl , -〇 (〇:!-C9) heteroaryl,-(C3-C7) cycloalkyl,-(c2-c9) heterocyclyl, -C02R7, -coNH2, -CONHR7, Hekou -CONR7R8 is replaced by a group; wherein, R7 and R8 in -CONR7R8 can form a-(c2-C9) heterocyclic group together with the linked atoms. 2. The compound according to item 1 of the scope of patent application, wherein R3 is hydrogen. 3. The compound according to item 1 in the scope of patent application, wherein R3 is selected from-(C6_C1 ()) aryl or-(C "C9) heteroaryl, and it is optionally selected from halogen, Hydroxyl,-(C ^ CJ alkyl,-(CrCd alkyl-P (〇) (〇 (^-(^ 6) 院 基) 2,-(C3-C1 ()) ring courtyard,-(CrC! .) Square group,-(C2-C9) heterocyclyl,-(CrCg) heteroaryl, -nr5r6, -NHSO ^ Ci-Cd alkyl, -NHS02 (C3-C6) cycloalkyl, -NUCrCj alkyl KSOJCrCe) alkyl), _N ((CrC6) alkyl) (S02 (C3-C6) cycloalkane • 204-200539871 (9) group), -N ((C3_C6) cycloalkylMSOjCrCe) alkyl), -N ((c3-c6) cycloalkyl) (s〇2 (c3-c6) cycloalkyl), -0 (C "C6) alkyl, -0-s〇2 (c) -c6) alkyl,- o-so2 (c3-c6) cycloalkyl,-(COMCrCjalkyl,-(CO) CF3,-(c〇) (c3-c10) cycloalkyl,-(CO) (C6-C10) aryl, -(CO) (C2-C9) heterocyclyl,-(COMCrCP heteroaryl,-(CO) O (Cr c6) alkyl, _ (co) o (c3-c1 ()) cycloalkyl,-( cc ^ cHCrG.) aryl,-(co) o (c2-c9) heterocyclyl,-(C〇) 〇 (Cl-C9) heteroaryl,-(CO) (C〗 -C6) alkyl -Od-Ce) alkyl-, -SOjCi-C6) alkyl, -S02 (c3-c6) ring Base, -S〇2CF3, -S02NH2, -SOjjNHiC ^ Ce) alkyl, -so2nh (c3-c6) cycloalkyl, -so2N ((c) -c6) alkyl) 2,-SOaNGC ^ -Ce) Group) ((C3-C6) ring courtyard base), -S02N ((C3-C6) ring courtyard base) 2, and -S02NR5R6 are replaced by the-(c6-C1Q) aryl group or- c9) Heteroaryl is arbitrarily interrupted by 1 to 3 units selected from -S-, -0-, -N-, -NH- and -NR12. 4. The compound according to item 1 of the patent application, wherein R3 is selected from ®- (c3-c1 ()) cycloalkyl,-(C2-C9) heterocyclyl, and-(Cl-c6) alkyl- (c2-C9) heterocyclyl, and it is optionally After 丨 to 3 are selected from halogen, hydroxyl,-(CrCJ alkyl,-(Ci-c6) alkyl-PaKCKCrCe) alkyl) 2,-(C3-c1 ()) cycloalkyl,-(C6- Ci.) Aryl,-(c2_c9) heterocyclyl,-(C〗 -C9) heteroaryl, -NR5R6, -NHSCMC〗 -c6) alkyl, -nhso2 (c3-c6) cycloalkyl, -N ((C 「C6) alkylHSOjCrCe) alkyl）, -N ((c 丨 -c6) alkyl) (S02 (C3-C6) cycloalkyl), -N ((c3-c6) cycloalkyl) (502 (< 31-(: 6) alkyl), -1 ^ ((〇3-0: 6) cycloalkyl) (50 ((:: 3-0: 6) cycloalkyl) , -〇 (C C6) alkyl, -O-SOjCrCe) alkyl, -0-s〇2 (c3- -205- 200539871 (10) c6) cycloalkyl,-(c〇) (c "c6) alkyl,-( c) cf3,-(c0) (c3-C10) cycloalkyl,-(c0) (c6-c). ) Aryl,-(co) (c2-c9) heterocyclyl,-(CO) (C "C9) heteroaryl,-(CC ^ CKCrCe) alkyl,-(co) o (c3-c1Q) ring Alkyl,-(C0) 0 (C6-C1 ()) aryl,-(co) o (c2-c9) heterocyclyl,-(CCOCHC ^ Cd heteroaryl,-(CO) (C 「C6) Alkyl-〇 (C "C6) alkyl-, -SCMC ^ -Ce) alkyl, -S02 (C3-C6) cyclofluorenyl, -S02CF3, -S02H2, -SC ^ NhUC ^ Ce) • alkyl, -S02NH (C3-C6) cycloalkyl, -SC ^ NGCrCe) alkyl) 2, -SC ^ NUC ^ -Ce) alkyl) ((C3_C6) cycloalkyl), -S02N ( (C3-C6) cycloalkyl) 2, and -so2nr5r6 are substituted, wherein-(c3-c1 ()) cycloalkyl,-(C2-C9) heterocyclyl, and-(CrCjalkyl -(c2-c9) heterocyclyl is optionally 1 to 3 units selected from-(C = 0), -S〇2, -S-, -〇-, -N-, -NH-, and -NR12 5. The compound according to item 1 of the scope of patent application, wherein R3 is-(C ^ -Ce) alkyl 'and it is arbitrarily selected from 1 to 3 selected from halogen, hydroxyl,-(Cr • C6) Alkyl,-(CrCj alkyl-PiOHCHC ^ -Ce) alkyl) 2, _ (C3-C10) cycloalkyl,-(c6-c1 ()) aryl,-(C2-C9) heterocyclyl, -(Crc9) heteroaryl, -NR5R6, mono-NHS02 (C "C6) alkane Group, -NHS〇2 (C3-C6) cycloalkyl, -alkylKSOjCrCd alkyl), -NGC ^ -Ce) alkyl) (S02 (C "C6) cycloalkyl), -N (( C3-C6) cycloalkyl) (S02 (C "C6) alkyl), -n ((c3-c6) cycloalkyl) (so2 (c3-c6) cycloalkyl), -0 (0]-( : 6) alkyl, -0-s〇2 (c "c6) alkyl, -0-S02 (c3-c6) cycloalkyl,-(COMCrc6) alkyl,-(co) cf3,-(co) (c3-c1 ()) cycloalkyl,-(C0) (c6-Cl.) aryl,-(CO) (C2-C9) heterocyclyl,-(COMC ^ -C,) -206- 200539871 ( 11) Heteroaryl,-(CC ^ CHCrCe) alkyl,-(C〇) 0 (C3-C1 ()) cycloalkyl,-((: 〇) 〇 ((: 6-(: 1.) aryl Group,-((: 〇) 〇 (0: 2-(: 9) heterocyclic group,-(CCOCMCrCg) heteroaryl,-(C〇) (C "C6) alkyl-CHCrCe) alkyl-,- SO ^ CrCe) alkyl, -S〇2 (c3-c6) cycloalkyl, -S〇2CF3, -s〇2nh2, -s〇2nh (c "c6) alkyl, -s〇2nh (c3-c6 ) Cycloalkyl, -S〇2N ((CrC6) alkyl) 2, -S〇2N ((C "C6) alkyl) ((C3-C6) cycloalkyl), -S〇2N ((C3- c6) cycloalkyl) 2, and -so2nr5r6 are substituted by #, wherein the-(C "C6) alkyl is arbitrarily 1 to 3 selected from-(c = 〇), -S 2, -s -, - N -, - NH - and -NR12 unit of interrupted. 6. The compound according to any one of items i to 5 of the scope of patent application, which is shown in the following formula 2: 其中A是選自下列基團： -207- 200539871 (12)Where A is selected from the group: -207- 200539871 (12) (R13)m 其中m是0至3之整數，及R13是選自氫、鹵素、羥基、 (Κ6)烷基、（C3-C7)環烷基、（C6-C1())芳基、（(^-(：9)雜 芳基、（C2-C9)雜環基、Ο-（CrCd烷基、0-（C3-C7)環烷基 、S02-(C「C6)烷基、S02-(C3 - C7)環烷基、nhso2(c】-c6) 烷基、NUC^-Ce)烷基 烷基）、N((C3-C7)環烷 -208 - 200539871 (13) 基）（S〇2(C】-c6)烷基）、N((Ci-c6)烷基）（s〇2(c3-c7)環烷基） 、N((C3-C7)環烷基）（s〇2(c3-c7)環烷基）、〇s〇2(c「c6)烷 基、S〇2CF3、S02NH2、SOzNmCrCd 烷基、S〇2NH(C3-C7)環烷基、S〇2NR5R6、so2n((c】-c6)烷基）2、cf3、co-(c】-c6)烷基、co — (c3一c7)環烷基、C〇CF3、c〇2(c】-c6)烷 基、(R13) m where m is an integer from 0 to 3, and R13 is selected from hydrogen, halogen, hydroxyl, (K6) alkyl, (C3-C7) cycloalkyl, (C6-C1 ()) aryl, ( (^-(: 9) heteroaryl, (C2-C9) heterocyclyl, 0- (CrCd alkyl, 0- (C3-C7) cycloalkyl, S02- (C "C6) alkyl, S02- (C3-C7) cycloalkyl, nhso2 (c) -c6) alkyl, NUC ^ -Ce) alkylalkyl), N ((C3-C7) cycloalkane-208-200539871 (13) yl) (S 〇2 (C) -c6) alkyl), N ((Ci-c6) alkyl) (s02 (c3-c7) cycloalkyl), N ((C3-C7) cycloalkyl) (s〇 2 (c3-c7) cycloalkyl), 〇〇〇2 (c 「c6) alkyl, S〇2CF3, S02NH2, SOzNmCrCd alkyl, S〇2NH (C3-C7) cycloalkyl, S〇2NR5R6, so2n ((c) -c6) alkyl) 2, cf3, co- (c) -c6) alkyl, co- (c3-c7) cycloalkyl, CoCF3, co2 (c) -c6) alkane base, 7 ·如申請專利範圍第1至5項中任一項之化合物，其係 如下式3所示： 07 · The compound according to any one of claims 1 to 5, which is represented by the following formula 3: 0 cf3 Bcf3 B 其中B是選自下列基團： -209- 200539871 (14)Where B is selected from the group: -209- 200539871 (14) 8 .如申請專利範圍第1至5項中任一項之化合物，其係 如下式4所示：8. The compound according to any one of claims 1 to 5 of the scope of patent application, which is represented by the following formula 4: cf3 D 4 -210- 0 200539871 (15) 其中D是選自下列基團：cf3 D 4 -210- 0 200539871 (15) where D is a group selected from: -211- 200539871 (16)-211- 200539871 (16) 其中q是1至2之整數。 9 .如申請專利範圍第1至5項中任一項之化合物，其 如下式5所示：Where q is an integer from 1 to 2. 9. The compound according to any one of claims 1 to 5 of the scope of patent application, which is represented by the following formula 5: 5 其中E是選自下式所示之基團： -212- 200539871 (17)5 where E is selected from the group consisting of: -212- 200539871 (17) 其中R14是選自（Ci-cj烷基、（c3-c7)環烷基、和（c2-c9)雜環基，及R15是選自氫、（CrC6)烷基' (C3-C7)環烷基 、和（c2-c9)雜環基。 • 1 〇 . —種化合物，其係選自下列： N -甲基-N - {3-[({甲基-[2-（2-酮-2,3-二氫-114-吲哚-5 -基胺基）_5_三氟甲基-嘧啶-4-基]-胺基})-甲基]-苯基}-甲磺醯胺； N -甲基-N-{4 -甲基 _3-[({甲基-[2-(2 -酮-2,3-二氫 _ 1H -卩引卩朵-5-基胺基）一 5-三氟甲基一喃陡-4 一基]一胺基}) 一甲基 ]-苯基}-甲磺醯胺； 1\1-(5-甲基-2-{[2-(2-酮-2,3-二氫-11^-卩弓丨[1朵-5-基胺 ^ 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_甲磺醯胺 f N-(3 -甲基-2-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 基）-5-三氟甲基-嘧啶_4_基胺基]-甲基卜苯基）-甲磺醯胺 f ]\1-（4-甲基-2-{[2_(2-_-2,3-二氫-114-〇引1]朵-5-基胺 基卜5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 N-(2 -甲基 _6-{[2-(2 -酮- 2,3 -二氫-1H-D引 D朵-5-基胺 -213- 9 200539871 (18) 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯胺 5 - [4-(3-甲磺醯基-两胺基）-5 -三氟ί甲基-嚼Π定-2-基 胺基]_ 1，3 -二氫-D引D朵-2 -酮； 1^-甲基-1^-（5-甲基-2-{[2-（2-嗣-2,3-二氨-11^-〇引晚-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺； N-(3-甲擴醯基胺基 _5-{[2-(2 -酮-2,3 -二氫-1H- ϋ引 口朵-5-基胺基）-5-三氟甲基-嘧Β定-4-基胺基]-甲基}-苯基）-甲磺醯胺； Ν -甲基-Ν-(4 -甲基-2-{[2 -（2- 嗣-2,3 -二氨-1H-D引噪-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺； N - 甲基-N -（2 -甲基 - 6_{[2_(2- 嗣 _2,3_二氨-1H - D引卩朵-5 -基胺基）-5 -三氟甲基-嘧D定-4-基胺基]-甲基卜苯基）-甲 _擴醯胺； N - 甲基-N -（3 -甲基-2-{[2 -（2- 嗣- 2,3 -二氮-1H-卩引 D朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_甲 磺醯胺； 5 - {4-[((lS，2R)-2 -經基-環己基甲基）-胺基]-5-三氟甲 基-嘧D定-2-基胺基卜1,3 -二氫-吲D朵-2-酮； 5 - [4-((lR，2S)-2-經基-節滿-1-基胺基）_5_三氟甲基-喃B定-2 -基胺基]-1，3 -二氫-吲D朵-2 -酮； 5 - [4-((S)-l-經甲基-2-苯基-乙胺基）-5 -三氟甲基-喃 -214- 200539871 (19) 啶-2-基胺基]-1,3-二氫-吲哚-2-酮； N-(3-(甲礎醯基-甲基-胺基）_5-{[2-(2-酮-2,3 -二氫-1H - P弓| D朵一 5-基胺基）一 5 -三氟甲基一 定一4 一基胺基]一甲基}一 苯基）-N-甲基-甲磺醯胺； 5-{4-[(1-羥基-環戊基甲基）-胺基]-5-三氟甲基-嘧 Π定- 2 -基胺基} - 1 , 3 -二氫-吲D朵-2 -酮； N-甲基- N-(3_{[2 -（2-酮 - 2,3-二氫-1H-吲哚-5-基胺 • 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲磺 醯胺； 1^1-（3-氟-2-{[2-(2-酮-2,3-二氫-114~^引卩朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-N-甲基-甲磺 醯胺； 5 - {4-[2-((S)_l -甲磺醯基-Π比略院-2-基）-乙胺基]-5-三氟甲基"喃Π定-2-基胺基}-1，3 -二氫-卩引卩朵-2-酮； 5 - {4-[(1-經基-環丁基甲基）-胺基]-5-三氟甲基-嘧 ^ 陡-2-基胺基}-1,3 -二氫-D引D朵-2 -酮； 5-{4-[2-((R)_l -甲擴醯基-Π比略院-2-基）-乙胺基]-5-三氟甲基-嘧卩定-2-基胺基}-1，3-二氫-卩引卩朵-2-酮； N -（2 -氟- 6- {[2-(2-酮-2,3-二氫-1H-D 引 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-N-甲基-甲磺 醯胺； N -（4 -氟- 2- {[2-(2-酮-2,3_ 二氫-1H-D 引 D朵-5-基胺基）-5-三氟甲基-嘧B定-4-基胺基]-甲基}-苯基）_N_甲基-甲磺 醯胺； -215- 200539871 (20) N- 甲基-N-(4-{[2-(2 -酮- 2,3 -二氫-1H -吲哚-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲磺 醯胺； N -{2,2-二甲基-3 - [2 -（2- 酮-2，3-二氫-1H-D弓 | D朵-5 -基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜N -甲基-甲磺 醯胺； ]^1-甲基-1\1-(6-{[2-（2-酮-2,3-二氫-114-卩弓丨0朵-5-基胺 ® 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲磺 醯胺； !^1-（2,4-二氟-6-{[2-(2-酮-2,3-二氫-11~1-卩引11朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_N_甲基-甲 磺醯胺； 5 - [4_((1R)-1-甲磺醯基B定-3_基胺基）-5-三氟甲 基-喃Π定-2-基胺基]-1,3 -二氫-D引D朵-2-酮； N - 甲基-N-(6 -甲基-3- {[2-(2_ 酮 -2,3-二氫-11-1-卩引哚-B 5-基胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基}-吡啶-2-基 )-甲磺醯胺； N-甲基- N_(5-{[2-(2 -酮 - 2,3 -二氫-1H- D引 D朵-5 -基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基）-甲磺 醯胺； 5 -[4-(1-甲磺醯基-哌啶-4-基胺基）-5-三氟甲基-嘧 D定- 2 -基胺基]-1，3 -二氫-吲哚-2 -酮； 5-{4-[甲基- ((R)-卜苯基-乙基）-胺基]-5-三氟甲基-嘧啶-2-基胺基卜1，3_二氫-吲哚-2-酮； -216- 200539871 (21) 5-（4-苯甲胺基-5-三氟甲基-嘧啶-2-基胺基）-1,3-二 氫-吲哚_ 2 -酮； N-(4,6-二甲基-3- {[2-(2 -嗣 _2,3_二氯-1H_D 引 D朵-5-基 胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-N_ 甲基-甲磺醯胺； 5-(4-第三丁基胺基-5-三氟甲基-嘧啶-2-基胺基）-1 , 3 -二氫-D引D朵-2 -酮； Φ 5-[4-((lR，5S,6S)-3-甲磺醯基-3 -氮雜-雙環[3.1.0] 己-6-基胺基）-5 -三氣甲基-嘧H定-2-基胺基]-1,3 -二氫-口弓丨 哚-2-酮； N-甲基-N-{3 -甲基-3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丁基卜甲磺醯胺 I N -（6- 甲基 - 3_{[2-(2 -酮-2,3 -二氫-1H -卩引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）-甲磺 •醯胺； 5 - {4-[(2 -甲擴醯基-卩比D定-4-基甲基）-胺基]-5 -三氟甲 基-嘧Π定-2-基胺基}_1，3 -二氫-卩引D朵-2-酮； 2 - [2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲 基-嘧啶-4-基胺基]-乙磺酸醯胺； N -（3-{甲基-[2-(2 -酮-2,3 -二氫-1H-D 引 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基]-胺基卜丙基）-甲磺醯胺； ]\1-（2-{甲基-[2-(2-酮-2,3-二氫-11~1-〇引1]朵-5-基胺基）-5-三氟甲基-嘧啶-4-基]-胺基卜乙基）-甲磺醯胺； -217- 200539871 (22) 5-[4-(2 -甲磺醯基甲基-苯甲胺基）-5-三氟甲基-嘧 D定- 2 -基胺基]-1 , 3 -二氫-D引D朵-2 -酮； 2-[2-(2 -酮- 2,3 -二氫-1H - D引B朵-5-基胺基）-5 -三氟甲 基-嘧啶-4-基胺基]-乙磺酸二甲醯胺； N -甲基-N-(3-{[2-(2 -酮 _2,3_ 二氫-1H-D引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基）-甲磺 醯胺； 乙磺酸甲基-(2_{[2-(2 -酮- 2,3 -二氫-1H -卩引D朵-5 -基胺 基）-5-三氟甲基-嘧D定-4-基胺基]-甲基卜苯基）-醯胺； 乙磺酸（2_{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-醯胺； N- 乙基-N-(3-{[2-(2 -酮-2,3 -二氫-1H-D引 D朵-5-基胺 基）-5 -三氟甲基-喃Π定-4-基胺基]-甲基卜卩比H定-2-基）-甲擴 醯胺； N-{1,1-二甲基-3-[2-(2 -酮-2,3 -二氫-1H -吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 1^-（5,6-二甲基-3-{[2-(2-嗣-2,3-二氫-114-卩弓丨卩朵_5-基 胺基）-5-三氟甲基-嘧D定-4-基胺基]-甲基卜卩比曉-2 -基）-N-甲基-甲磺醯胺； 5-{4-[((R)-4_甲擴醜基-嗎啉-3-基甲基）-胺基]-5 -三 氟甲基-嘧啶-2-基胺基卜1,3-二氫-吲哚-2-酮； 丙院-1-擴酸（2_{[2-(2 -酮- 2,3 -二氫-1H-D引D朵-5-基胺 基）-5-三氟甲基密B定-4-基胺基]-甲基卜苯基）-醯胺； 5-{4-[2-((R)-4-甲磺醯基-嗎啉-3-基）-乙胺基卜5-三 -218- 200539871 (23) 氟甲基-嘧啶-2-基胺基卜1，3-二氫-吲哚-2-酮； 乙磺酸甲基-(3-{[2-(2-酮- 2,3-二氫-1H-吲哚-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基）_醯胺 三氟-N-甲基-N-{3-[2_(2-酮 -2,3-二氫-114-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 環丙烷磺酸甲基-{3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-® 基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜醯胺； N - 乙基-N-(2_ {[2 -（2-酮-2,3-二氨-1H-卩引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基卜甲基卜苯基）-甲磺醯胺 t 乙磺酸甲基-（5 -甲基-2-{[2-(2-酮- 2,3-二氫-1H-吲 口朵-5-基胺基）-5-三氟甲基-嘧陡-4-基胺基]-甲基}-苯基）-醯胺； 乙擴酸乙基-(2-{[2-(2 -酮- 2,3 -二氫-1H -卩引卩朵-5-基胺 ^ 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-醯胺； 乙磺酸乙基-（5_甲基-2-{[2-(2-酮- 2,3-二氫-1H-吲 D朵-5-基胺基）-5 -三氟甲基-喃Π定-4-基胺基]-甲基卜苯基）-醯胺； Ν- 乙基-Ν -（5-甲基-2-{[2-（2- 嗣-2,3- 二氯-1H-D引 D朵-5-基胺基）_5_三氟甲基-喷啶-4-基胺基]-甲基卜苯基）-甲 磺醯胺； 乙磺酸（5-甲基-2_{[2-(2_酮- 2,3-二氫-1Η-吲哚-5-基 胺基）-5-三氟甲基-嘧啶_4-基胺基]-甲基卜苯基）-醯胺； -219- 200539871 (24) 乙磺酸（3-甲基- 2-{[2-(2-酮- 2,3-二氫_1H-吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）_醯胺； 乙磺酸甲基-（3 -甲基-2-{[2-(2-酮-2,3-二氫-1H-吲 哚-5-基胺基）-5_三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-醯胺； 2-[2_(2-酮-2,3_二氫-1卜日引0朵-5-基胺基）-5_三氟甲 基-嘧啶-4-基胺基]-乙磺酸甲醯胺； 乙擴酸{3-[2-(2_酮- 2,3 -二氫-1H -卩引卩朵_5_基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜醯胺； C-甲磺醯基- N-{3-[2-(2-酮- 2,3-二氫-1H-吲哚-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜甲磺醯胺； 乙擴酸{2-[2-(2_酮- 2,3 -二氫-1H -卩引卩朵-5-基胺基）-5-三氟甲基-嘧定-4-基胺基]-乙基卜醯胺； C- 甲擴醯基- Ν_{2-[2 -（2 -酮- 2,3 -二氫-1H-D引 D朵-5- 基 胺基）-5 -三氟甲基-嘧D定-4 -基胺基]-乙基}-甲擴醯胺； Ν -甲基-Ν-（4-甲基-3 - {[2-(2-酮-2,3-二氫-114-吲哚-5 -基胺基）-5 -三氟甲基-喃Π定-4-基胺基]-甲基}-卩比Π定-2-基 )-甲磺醯胺； 5-(4-{[1-(2,2,2-三氟-乙醯基）-哌啶-3-基甲基]-胺基 }-5 -三氣甲基-嘧D定-2-基胺基）-1,3 -二氫-卩引卩朵-2-酮； 2,2,2-三氟-乙磺酸{3-[2-(2-酮- 2,3-二氫-ΙΗ-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-丙基卜醯胺； N- 甲基- N- (4_{[2-(2- 酮-2,3 -二氫-1H-D 引 D朵 - 5-基胺 基）_5-三氟甲基-嘧啶-4-基胺基]-甲基}_嘧啶-2-基）_甲磺 -220- 200539871 (25) 醯胺； 1^-環丙基-1^-（2-{[2-（2-酮-2,3-二氫-1}4-卩引[1朵-5-基 胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜苯基）-甲磺醯 胺； N -甲基-N-(2-{[2_(2 -酮-2,3 -二氫-1H-D引 D朵-5-基胺 基）_5_三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基）-甲磺 醯胺； ^^-甲基-1^-(6-{[2-(2_酮-2,3-二氫-114-〇引|]朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基）-甲磺 醯胺； 1^-甲基-1^-(2-{[2-(2-酮-2,3-二氫-11^-卩引11朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基）-甲磺 醯胺； N- 甲基-N-(3_{[2-(2 -酮- 2,3 -二氫-1H -卩引 D朵-5_ 基胺 基）-5 -三氟甲基-喃Π定-4-基胺基]-甲基卜卩比Π定-4-基）-甲擴 醯胺； 1^-環丙基-1^-（3-{[2-（2-酮-2,3-二氮-114-卩引1]朵-5-基 胺基）-5-三氟甲基_嘧啶-4-基胺基]-甲基卜吡啶-2_基）-甲 磺醯胺； N -甲基-N -（6 -甲基-3-{[2 -（2-酮- 2,3-二氫-lH-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基 )-甲磺醯胺； 5-{4-[(2 -甲磺酿基甲基-卩比卩定_3_基甲基）-胺基]_5-三 氟甲基-IP密Π定-2-基胺基卜1,3 -二氬-D引D朵_2_酮； -221 - 200539871 (26) 1\!-甲基-]^-(4-{[2-(2-酮-2,3-二氫-11~1-卩弓^朵-5-基胺 基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基）_甲磺 醯胺； N -甲基- N-(3- 甲基-6-{[2 -（2- 嗣-2,3-二氫-lH-D引噪-5_基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-吡啶-2·基 )-甲磺醯胺； N-甲基-N -（5 - 甲基-3 - {[2 -（2-嗣-2,3- 二氮-1H~D弓丨噪-^ 5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； N -甲基-N -（4-甲基-6 - {[2 -（2-嗣-2,3-二氯-1H -卩引卩朵-5 -基胺基）-5-三氟甲基-喃Π定-4-基胺基]-甲基}-卩比D定-2-基 )-甲磺醯胺； Ν- 甲基-Ν-（2-甲基-5-{[2 -（2- 嗣-2,3-二氮-1Η - D引 D朵-5 -基胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )-甲磺醯胺； 1]\]-甲基-1^-（5-甲基-6-{[2-(2-嗣-2,3-二氮-114-卩弓丨11朵_ 5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； N-甲基-N -（6 -甲基 - 2_{[2 -（2-酮-2,3-二氫-114-吲哚-5 -基胺基）_5_三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )-甲磺醯胺； N- 甲基-N -（5- 甲基 ~2-{[2-（2 -嗣-2,3- 二氫-1H-卩引 D朵-5 -基胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 甲磺醯胺； -222- 200539871 (27) ^^-甲基-1^-（5-甲基-2-{[2-（2-酮-2,3-二氫-1^1-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-3-基 )_甲磺醯胺； N -甲基-N-(4-甲基- 2-{[2-（2-酮-2,3-二氫-lH-吲哚-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基}-吡啶-3_基 )-甲磺醯胺； N -甲基-N-(3-甲基 - 4- {[2 -（2 -嗣 - 2,3-二氨-1H-D 引口朵-® 5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶_2-基 )-甲磺醯胺； N-甲基-N-(5-甲基-4-{[2 -（2 -嗣- 2,3-二氨-1H_卩引卩朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-2-基 )-甲磺醯胺； N-甲基- N- (6-甲基-5 - {[2-（2- 嗣-2,3-二氨-1H-D 引 D朵-5 -基胺基）-5 -三氟甲基-嘧U定-4-基胺基]-甲基}-卩比Π定-3-基 )-甲磺醯胺； 11^-甲基-1^-(6-甲基-2-{[2-（2-酮-2,3-二氫-114-吲哚-5 -基胺基）-5 -三氟甲基-喃U定-4 -基胺基]-甲基}-嘧Π定-4-基 )-甲磺醯胺； 1甲基-1^-(5-甲基-4-{[2-(2-酮-2,3-二氫-1}~[-卩引哚-5-基胺基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-2-基 )-甲磺醯胺； N-甲基- N-(2-甲基- 3-{[2-(2-酮 _2,3-二氫-1H-吲哚-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡啶-4-基 )-甲磺醯胺； -223- 200539871 (28) 1\1_甲基-1^-（6-甲基_4-{[2-（2-嗣-2,3-二氣-11-1-卩引噪-5 -基胺基）-5 -三氟甲基-II·密Π定-4 -基胺基]-甲基卜卩J± Π定-2-基 )-甲磺醯胺； ]^]-甲基-1^-（5-甲基-3-{[2_(2-酮-2,3-二氫-114-卩弓丨噪-5-基胺基）-5_三甲基-喃U定-4 -基胺基]-甲基}-卩比Β定-4-基 )-甲磺醯胺； ^1-甲基-1^-（5-甲基-6-{[2-（2-嗣-2,3-二氨_114_卩引卩朵-^ 5 -基胺基）-5 -三氟甲基-嘧Π定-4-基胺基]-甲基卜喃Π定-4-基 )-甲磺醯胺； 1^-甲基-1^_(5-甲基-4-{[2_(2_嗣_2,3_二氮-11^_卩引卩朵-5 -基胺基）-5_三氟甲基-喃D定-4-基胺基]-甲基}-卩比Π定-3-基 )-甲磺醯胺； N-甲基-N_(6 - {[2-（2- 酮-2,3-二氫-1H-D 引卩朵 - 5- 基胺 基）_5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基）·_甲磺 醯胺； •]\]-甲基_1^-(6-甲基-4-{[2-(2-嗣一2,3-二氨一1}4-卩弓|卩朵-5 -基胺基）-5 -三氟甲基-嘧Π定-4-基胺基]-甲基}-嘧Π定-2-基 )-甲磺醯胺； N -甲基-N-(2-甲基 _4-{[2-（2 -嗣-2,3 -二氨-1H -卩引 D朵-5 -基胺基）-5 -三氟甲基-嘧Π定-4-基胺基]-甲基卜D比陡-3-基 )-甲磺醯胺； N-甲基-N -(5-{[2 -（2-酮-2,3-二氫-1H-D 引 D朵-5-基胺 基）-5-三氟甲基-嘧啶-4-基胺基]_甲基卜嘧啶-4-基）-甲磺 醯胺； -224 - 200539871 (29) N -甲基-（2- 甲基-6- {[2-（2- 嗣 - 2,3 -二氯-1H - B引卩朵-5 -基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺； 1^-甲基-1^-（6-甲基-4-{[2-（2-嗣-2,3-二氬-114-〇引[]朵-5 -基胺基卜5 -三氟甲基-嚼U定-4-基胺基]-甲基}-卩比B定-3-基 )-甲磺醯胺； 1^-甲基-1^-（4-{[2-（2-酮-2,3-二氫-114-卩弓丨卩朵-5-基胺 基）-5-三氟甲基-嘧H定-4-基胺基]-甲基丨-ll·密II定-5-基）-甲磺 醯胺； !^-甲基-1^_(2-甲基-5-{[2-(2-酬-2,3-二氨-1^1-〇弓丨11朵-5 -基胺基）-5_三氣甲基-喃D定-4-基胺基]甲基卜嘧U定-4-基 )-甲磺醯胺； N- 甲基-N -（4 - 甲基-6 - {[2-（2 -嗣- 2,3 - 二氯-1H-D 弓丨 D朵-5 -基胺基）-5 -三氣甲基-嘧、Π定-4-基胺基]-甲基}-嘧B定-5-基 )-甲磺醯胺； N- 甲基- N_(5 -甲基 - 6- {[2-（2- 嗣-2,3 - —氫-1H-卩引 D朵-5 -基胺基卜5_三氟甲基-赔B定-4-基胺基]-甲基卜卩比嗪-2-基 )-甲磺醯胺； N - 甲基-N -（5_甲基 -3-{[2-（2-嗣-2,3-二氨-11~1-0引0朵-5 -基胺基）_5 -三贏甲基-嘧D定-4-基胺基]-甲基卜卩仕曉-2-基 )-甲磺醯胺； N-甲基-N -（2-甲基-6-{[2-（2-酮 - 2,3-二氫-114-吲哚-5 -基胺基）-5 -三氟甲基-嘧D定-4-基胺基]-甲基卜嚼B定-5-基 )-甲磺醯胺； -225- 200539871 ί.^Π) Ν -甲基-Ν- (3-甲基-6- {[2-(2 -酮- 2,3 -二氫-1Η-吲 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜吡嗪-2-基 )-甲磺醯胺；及 N -甲基-N_(6 -甲基-5_{[2-（2_嗣-2,3-二氯-1H-D引 D朵-5-基胺基）-5-三氟甲基-嘧啶-4-基胺基]-甲基卜嘧啶-4-基 )-甲磺醯胺。 1 1 . 一種申請專利範圍第1項之化合物於製備用於治療 ^ 哺乳動物之異常細胞生長的藥物上之用途。 1 2 . —種用於治療哺乳動物之異常細胞生長之藥學組 成物，其包含治療異常細胞生長有效量之如申請專利範圍 第1項之化合物，及藥學上可接受之載體。Where R14 is selected from (Ci-cj alkyl, (c3-c7) cycloalkyl, and (c2-c9) heterocyclyl, and R15 is selected from hydrogen, (CrC6) alkyl '(C3-C7) ring Alkyl, and (c2-c9) heterocyclyl. • 1 10. A compound selected from the group consisting of the following: N -methyl-N-{3-[({methyl- [2- (2-one -2,3-dihydro-114-indole-5-ylamino) -5_trifluoromethyl-pyrimidin-4-yl] -amino})-methyl] -phenyl} -methanesulfonamide ; N -methyl-N- {4 -methyl_3-[({methyl- [2- (2-keto-2,3-dihydro_1H-pyridin-5-ylamino)) Mono-5-trifluoromethyl-monoan-4 monoyl] monoamino}) monomethyl] -phenyl} -methanesulfonamide; 1 \ 1- (5-methyl-2-{[2- (2-keto-2,3-dihydro-11 ^ -fluorene) [1-5-ylamine ^ yl] -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbenzene ) _Methanesulfonamide f N- (3-methyl-2-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoro Methyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide f] \ 1- (4-methyl-2-{[2_ (2 -_- 2,3-dihydro -114-〇 引 1] Do-5-ylamino group 5-trifluoromethyl-pyrimidin-4-ylamino group] -methylbuphenyl) -methanesulfonamide N- (2-methyl_ 6-{[2- (2- -keto-2,3 -dihydro- 1H-D D-5-ylamine-213- 9 200539871 (18) yl) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide 5 -[4- (3-Methanesulfonyl-diamino) -5 -trifluoromethyl-methylidene-2-ylamino] _ 1,3-dihydro-D Ketone; 1 ^ -methyl-1 ^-(5-methyl-2-{[2- (2-fluorene-2,3-diamino-11 ^ -〇valent late-5 -ylamino) -5 -Trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine; N- (3-methylexpanylamino_5-{[2- (2 -one- 2,3 -dihydro-1H- fluorene introductor-5-ylamino group) -5-trifluoromethyl-pyrimidine-4-ylamino group] -methyl} -phenyl) -methanesulfonyl Amine; N-methyl-N- (4-methyl-2-{[2-(2-fluorene-2,3-diamino-1H-D noise-inducing 5--aminoamino) -5-trifluoro Methyl-pyrimidin-4-ylamino] -methylbuphenyl) -methanesulfonamide; N -methyl-N-(2-methyl-6 _ {[2_ (2- 嗣 _2,3_ Diamino-1H-D (indo-5 -ylamino) -5 -trifluoromethyl-pyrimidinyl-4-ylamino] -methylphenylphenyl) -methyl-amidine; N- Methyl-N-(3-methyl-2-{[2--(2-fluorene-2,3 -diazine-1H-fluorene) -5 -ylamino) -5-trifluoromethyl- Pyrimidin-4-ylamino] -methylphenyl _Methanesulfonamide; 5-{4-[((lS, 2R) -2 -Ethyl-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino Bu 1,3 -dihydro-inddodol-2-one; 5-[4-((lR, 2S) -2-Cyclo-pentan-1-ylamino) _5_trifluoromethyl-an B-Amine-2 -ylamino] -1,3-dihydro-indodo-2 -one; 5-[4-((S) -l-methyl-2-phenyl-ethylamino) -5 -trifluoromethyl-ran-214- 200539871 (19) pyridin-2-ylamino] -1,3-dihydro-indole-2-one; N- (3- (formylfluorenyl- Methyl-amino) _5-{[2- (2-keto-2,3 -dihydro-1H-P bow | D-a-5-ylamino) -5-trifluoromethyl must be a 4-group Amine] -methyl} -phenyl) -N-methyl-methanesulfonamide; 5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl -Pyrimidine- 2 -ylamino}-1, 3 -dihydro-indodo-2 -one; N-methyl-N- (3 _ {[2-(2-one-2,3-di Hydrogen-1H-indole-5-ylamine • yl) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide; 1 ^ 1- (3-fluoro-2-{[2- (2-keto-2,3-dihydro-114 ~ ^ indo-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamine Phenyl] -methylbuphenyl) -N-methyl-methanesulfonamide 5-{4- [2-((S) _l -Methanesulfonyl-II Billioin-2-yl) -ethylamino] -5-trifluoromethyl " } -1,3 -dihydro-pyridin-2-one; 5-{4-[(1-Eryl-cyclobutylmethyl) -amino] -5-trifluoromethyl-pyrimidine -2-ylamino} -1,3 -dihydro-D-D-2-2-one; 5- {4- [2-((R) _l -Methylsulfenyl-II-bileline-2- ) -Ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-pyridin-2-one; N-(2-fluoro-6 -[[2- (2-Keto-2,3-dihydro-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbull Phenyl) -N-methyl-methanesulfonamide; N- (4-fluoro- 2-{[2- (2-keto-2,3_dihydro-1H-D) ) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -phenyl) _N_methyl-methanesulfonamide; -215- 200539871 (20) N-methyl-N -(4-{[2- (2-keto-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl Pyridin-2-yl) -methanesulfonamide; N-{2,2-dimethyl-3-[2-(2-keto-2,3-dihydro-1H-D bow | DDO-5 -Ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanyl N-methyl- Sulfonamide;] ^ 1-methyl-1 \ 1- (6-{[2- (2-keto-2,3-dihydro-114-pyrenium 丨 0-5-ylamine® group)- 5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide;! ^ 1- (2,4-difluoro-6-{[2- ( 2-keto-2,3-dihydro-11 ~ 1-pyrene 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) _N _Methyl-methanesulfonylamine; 5-[4 _ ((1R) -1-methanesulfonylB-dio-3_ylamino) -5-trifluoromethyl-annino-2-ylamino ] -1,3 -Dihydro-D-D-Dan-2-one; N -methyl-N- (6-methyl-3- {[2- (2_ ketone-2,3-dihydro-11- 1-pyridine-B 5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyridin-2-yl) -methanesulfonylamine; N-methyl- N_ (5-{[2- (2- (2-keto-2,3-dihydro-1H-D) -5 (5-amino))-5-trifluoromethyl-pyrimidin-4-ylamino]- Methylpyridin-3-yl) -methanesulfonylamine; 5- [4- (1-methylsulfonyl-piperidin-4-ylamino) -5-trifluoromethyl-pyrimidine-2 -Ylamino] -1,3-dihydro-indole-2 -one; 5- {4- [methyl-((R) -phenylphenyl-ethyl) -amino] -5-trifluoro Methyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2-one; -216- 200539871 (21) 5- (4-benzylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole-2-one; N- (4,6- Dimethyl-3- {[2- (2- -2-_2,3_dichloro-1H_D D-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -formyl Pyridin-2-yl) -N-methyl-methanesulfonamide; 5- (4-Third-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1, 3- Dihydro-D, D-D- 2 -one; Φ 5- [4-((lR, 5S, 6S) -3-methylsulfonyl-3 -aza-bicyclo [3.1.0] hexa-6-yl Amine) -5 -trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-orbinoindol-2-one; N-methyl-N- {3-methyl -3- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -butyltrimethylene Sulfonamide IN-(6-methyl-3 _ {[2- (2-keto-2,3 -dihydro-1H-pyridin-5-ylamino) -5-trifluoromethyl-pyrimidine 4-ylamino] -methylpyridin-2-yl) -methanesulfonylamine; 5-{4-[(2-methylsulfanyl-fluorenyl-D-A-4-ylmethyl)- Amine] -5 -trifluoromethyl-pyrimidine-2-ylamino} _1,3-dihydro-pyridin-2-one; 2-[2- (2-one-2,3 -Dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -ammonium ethanesulfonate; N-(3- {methyl- [2- (2-keto-2,3-dihydro-1H-D) -5-trifluoromethyl-pyrimidin-4-yl] -aminopropylpropyl) -methanesulfonamide;] \ 1- (2- {methyl- [2- (2-one-2,3-dihydro -11 ~ 1-〇 prime 1] Duo-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -aminobuethyl) -methanesulfonamide; -217- 200539871 (22) 5 -[4- (2-Methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyridine-2,2-aminoamino] -1, 3 -dihydro-D 2-ketone; 2- [2- (2-keto-2,3-dihydro-1H-D-B-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Dimethylammonium ethanesulfonate; N -methyl-N- (3-{[2- (2-keto_2,3_dihydro-1H-D-D-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -methylpyrazin-2-yl) -methanesulfonamide; methyl ethanesulfonate- (2 _ {[2- (2 -one-2,3 -Dihydro-1H -pyridine-5 -ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; ethanesulfonic acid ( 2 _ {[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenyl ) -Amidamine; N-ethyl-N- (3-{[2- (2- -2,3 -dihydro-1H-D-D-5-ylamino) -5 -trifluoromethyl-annidine-4-ylamino] -methylbutyrate Hdin-2- ) -Methanamine; N- {1,1-dimethyl-3- [2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -propylbenzamidine; 1 ^-(5,6-dimethyl-3-{[2- (2-fluorene-2,3-di Hydrogen-114- 卩 丨 卩 朵 _5-ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino group] -methylbubipyroxy-2 -yl) -N-formyl -Methanesulfonylamine; 5- {4-[(((R) -4_methanyl-morpholin-3-ylmethyl) -amino group] -5 -trifluoromethyl-pyrimidine-2- Aminoamino group 1,3-dihydro-indole-2-one; Glycyl-1-propanoic acid (2 _ {[2- (2-keto-2,3-dihydro-1H-D) 5-ylamino) -5-trifluoromethylpyridin-4-ylamino] -methylbuphenyl) -fluorenamine; 5- {4- [2-((R) -4-methyl Sulfonyl-morpholin-3-yl) -ethylaminob 5-tri-218- 200539871 (23) fluoromethyl-pyrimidin-2-ylaminob 1,3-dihydro-indole-2- Ketone; methyl ethanesulfonate- (3-{[2- (2-keto-2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Aminoamino] -methylpyridin-2-yl) _amidotrifluoro-N-methyl-N- {3- [2_ (2 -Keto-2,3-dihydro-114-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylmethanesulfonamide; cyclopropanesulfonic acid Methyl- {3- [2- (2-keto-2,3-dihydro-1H-indole-5-®aminoamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propylbutamidine; N-ethyl-N- (2_ {[2-(2-keto-2,3-diamino-1H-pyridin-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylaminomethylmethylphenylphenyl) -methanesulfonamide t-methylsulfonic acid methyl- (5-methyl-2-{[2- (2-keto-2,3-dihydro- 1H-indoxo-5-ylamino) -5-trifluoromethyl-pyrimidino-4-ylamino] -methyl} -phenyl) -fluorenamine; ethyl acetamate- (2- {[2- (2-keto-2,3-dihydro-1H-pyridin-5-ylamine ^ yl) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbull Phenyl) -fluorenamine; Ethyl ethanesulfonate- (5-methyl-2-{[2- (2-keto-2,3-dihydro-1H-indodol-5-ylamino)- 5 -trifluoromethyl-anidin-4-ylamino] -methylbuphenyl) -fluorenamine; N-ethyl-N- (5-methyl-2-{[2- (2- Fluorene-2,3-dichloro-1H-D-D-5-ylamino) _5_trifluoromethyl-pentidin-4-ylamino] -methylphenylphenyl) -methanesulfonylamine Ethanesulfonic acid (5-methyl-2 _ {[2- (2-keto-2,3-dihydro-1fluoren-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; -219- 200539871 (24) ethanesulfonic acid (3-methyl-2- 2-[[2- (2-keto-2,3-dihydro_1H-indole-5-ylamino) -5-trifluoro Methyl-pyrimidin-4-ylamino] -methylbuphenyl) -amidine; methyl ethanesulfonate- (3-methyl-2-{[2- (2-keto-2,3-di Hydrogen-1H-indole-5-ylamino) -5_trifluoromethyl-pyrimidin-4-ylamino] -methylbuphenyl) -fluorenamine; 2- [2_ (2-one-2 , 3_dihydro-1bzr 0-5-ylamino group) -5_trifluoromethyl-pyrimidin-4-ylamino group] -methylsulfonium ethanesulfonate; acetic acid {3- [ 2- (2_keto-2,3 -dihydro-1H-pyridine_5_ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamine; C-methanesulfonyl-N- {3- [2- (2-keto-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Propylamino] -propyl sulfasalazine; Ethanoic acid {2- [2- (2-keto-2,3 -dihydro-1H-pyridin-5-ylamino) -5- Trifluoromethyl-pyrimidin-4-ylamino] -ethylbutanamine; C-methanyl-N_ {2- [2-(2-keto-2,3 -dihydro-1H-D D--5-ylamino) -5 -trifluoromethyl- D-A-4 -ylamino] -ethyl} -methanamine; N-methyl-N- (4-methyl-3-{[2- (2-keto-2,3-dihydro- 114-indole-5 -ylamino) -5 -trifluoromethyl-pyridin-4-ylamino] -methyl} -pyridinyl-2-yl) -methanesulfonylamine; 5 -(4-{[1- (2,2,2-trifluoro-ethylfluorenyl) -piperidin-3-ylmethyl] -amino} -5 -trifluoromethyl-pyridine-2- Amino group) -1,3-dihydro-pyridin-2-one; 2,2,2-trifluoro-ethanesulfonic acid {3- [2- (2-keto-2,3-dihydro -I-Indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propylbutanamine; N-methyl-N- (4 _ {[2- (2 -Keto-2,3 -dihydro-1H-D-5-ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} _pyrimidin-2-yl) _ Methanesulfonyl-220- 200539871 (25) hydrazine; 1 ^ -cyclopropyl-1 ^-(2-{[2- (2-keto-2,3-dihydro-1) 4-pyrene [1 flower -5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylphenylphenyl) -methanesulfonamide; N-methyl-N- (2-{[2_ ( 2 -keto-2,3 -dihydro-1H-D-D-5-ylamino) _5_trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl)- Methanesulfonamide; ^^-methyl-1 ^-(6-{[2- (2_one-2,3-dihydro-114-〇 引 |] 朵- 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylplpyrazin-2-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-(2 -[[2- (2-keto-2,3-dihydro-11 ^ -pyrene 11-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl Pyridin-3-yl) -methanesulfonylamine; N-methyl-N- (3 _ {[2- (2-keto-2,3 -dihydro-1H-pyridin-5-ylamino)) -5 -trifluoromethyl-pyridin-4-ylamino] -methylpyridinium-4-yl) -methanesulfonylamine; 1 ^ -cyclopropyl-1 ^-(3- {[2- (2-keto-2,3-diaza-114-pyridine 1] Duo-5-ylamino) -5-trifluoromethyl_pyrimidin-4-ylamino] -methylbu Pyridin-2-yl) -methanesulfonamide; N-methyl-N- (6-methyl-3-{[2-(2-keto-2,3-dihydro-lH-indole-5- Aminoamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrazin-2-yl) -methanesulfonamide; 5- {4-[(2-methylsulfonyl Methyl-pyridine_3_ylmethyl) -amino group] _5-trifluoromethyl-IP melidin-2-ylamino group 1,3-diargon-D Ketones; -221-200539871 (26) 1 \!-Methyl-] ^-(4-{[2- (2-keto-2,3-dihydro-11 ~ 1-pyrene ^ Do-5-yl Amine) _5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-3-yl ) _Methanesulfonylamine; N -methyl-N- (3-methyl-6-{[2-(2- fluorene-2,3-dihydro-lH-D noise-inducing-5_ylamino group) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -pyridine-2 · yl) -methanesulfonamide; N-methyl-N-(5 -methyl-3-{[ 2-(2- 嗣 -2,3-diaza-1H ~ D bow Noise- ^ 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridine- 2-yl) -methanesulfonamide; N -methyl-N-(4-methyl-6-{[2-(2-fluorene-2,3-dichloro-1H -pyridine-5- Ylamino) -5-trifluoromethyl-anidino-4-ylamino] -methyl} -fluorene than D din-2-yl) -methanesulfonylamine; N-methyl-N- ( 2-methyl-5-{[2-(2- fluorene-2,3-diazine-1 fluorene-dimethylamino-5 -ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino ] -Methylpyridin-3-yl) -methanesulfonamide; 1] \]-methyl-1 ^-(5-methyl-6-{[2- (2-fluorene-2,3-di Nitrogen-114-fluorene 丨 11 _ 5 -ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide; N- Methyl-N- (6-methyl-2 _ {[2- (2-keto-2,3-dihydro-114-indole-5-ylamino) _5_trifluoromethyl-pyrimidine-4- Methylamino] -methylpyridin-3-yl) -methanesulfonamide; N-methyl- N-(5-methyl ~ 2-{[2- (2 -fluorene-2,3-dihydro-1H-fluorene D-5-5-ylamino) _5-trifluoromethyl-pyrimidine-4- Aminoamino] -methylpyrimidin-4-ylmethanesulfonamide; -222- 200539871 (27) ^ -methyl-1 ^-(5-methyl-2-{[2- (2-one -2,3-dihydro-1 ^ 1-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-3-yl) _methanesulfonate Amidoamine; N-methyl-N- (4-methyl- 2-{[2- (2-keto-2,3-dihydro-lH-indole-5-ylamino) -5-trifluoro Methyl-pyrimidin-4-ylamino] -methyl} -pyridine-3_yl) -methanesulfonamide; N-methyl-N- (3-methyl- 4- {[2-(2-嗣-2,3-Diamino-1H-D Introduced-® 5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridine_2-yl)- Methanesulfonamide; N-methyl-N- (5-methyl-4-{[2--(2- -2-2,3-diamino-1H_ 卩 Amino-5 -ylamino)- 5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-2-yl) -methanesulfonamide; N-methyl-N- (6-methyl-5-{[2- (2-fluorene-2,3-diamino-1H-D) -5-triaminomethyl) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -fluorene ratio Π 定 -3-yl) -methanesulfonamide; 11 ^ -methyl-1 ^-(6-methyl-2-{[2- (2- -2,3-dihydro-114-indole-5 -ylamino) -5 -trifluoromethyl-uridine-4 -ylamino] -methyl} -pyrimidine-4-yl) -Methanesulfonamide; 1methyl-1 ^-(5-methyl-4-{[2- (2-keto-2,3-dihydro-1} ~~ -indole-5-ylamine ) _5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-2-yl) -methanesulfonamide; N-methyl-N- (2-methyl- 3-{[ 2- (2-keto_2,3-dihydro-1H-indole-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyridin-4-yl ) -Methanesulfonamide; -223- 200539871 (28) 1 \ 1_methyl-1 ^-(6-methyl_4-{[2- (2-fluorene-2,3-digas-11- 1-fluorene octyl-5 -ylamino) -5 -trifluoromethyl-II · mididin-4 -ylamino] -methylbutyridine J ± Πdin-2-yl) -methanesulfonyl Amine;] ^]-methyl-1 ^-(5-methyl-3-{[2_ (2-keto-2,3-dihydro-114-fluorene-5-methylamino) -5 _Trimethyl-pyridine-4-ylamino] -methyl} -fluorene than bismethyl-4-yl) -methanesulfonylamine; ^ 1-methyl-1 ^-(5-methyl- 6-{[2- (2- 嗣 -2,3-Diamino_114_ 卩 卩-^ 5--aminoamino) -5 -trifluoromethyl-pyrimidine-4-ylamino] -Methylpropanyl-4-yl) -methanesulfonamide; 1 ^ -methyl-1 ^ _ (5-methyl-4-{[2_ (2_ 嗣 _2,3_diazine- 11 ^ _ Indole-5 -ylamino) -5_trifluoromethyl-anhydrol-d-4-ylamino] -methyl} -pyridine-3-yl) -methanesulfonylamine; N- Methyl-N_ (6-{[2- (2-keto-2,3-dihydro-1H-D indole-5 -ylamino) _5-trifluoromethyl-pyrimidin-4-ylamino ] -Methylpyrimidin-4-yl) · _methanesulfonamide; •] \]-methyl_1 ^-(6-methyl-4-{[2- (2-fluorenone-2,3- Diammonium-1} 4-methylpyridine | pentyl-5 -ylamino) -5 -trifluoromethyl-pyrimidine-4-ylamino] -methyl} -pyrimidine-2-yl) -Methanesulfonylamine; N -methyl-N- (2-methyl_4-{[2- (2- -fluorene-2,3-diamino-1H -pyridine-5 -ylamino)) -5 -trifluoromethyl-pyrimidin-4-ylamino] -methylbutadione-3-yl) -methanesulfonamide; N-methyl-N-(5-{[2- (2-keto-2,3-dihydro-1H-D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] _methylpyrimidin-4-yl ) -Methanesulfonamide; -224-200539871 (29) N -methyl- (2-methyl-6- {[2- (2- fluorene-2,3 -dichloro-1H -B)- 5-methylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl) -methanesulfonamide; 1 ^ -methyl-1 ^-(6- Methyl-4-{[2- (2-fluorene-2,3-diargon-114-〇 引 [] 朵 -5- Aminoamino group 5 -trifluoromethyl-methylidene-4-ylamino] -methyl} -fluorenyl than Bden-3-yl) -methanesulfonylamine; 1 ^ -methyl-1 ^- (4-{[2- (2-keto-2,3-dihydro-114-fluorenyl-5-methylamino) -5-trifluoromethyl-pyrimidine-4-ylamino ] -Methyl 丨 -ll · Mid II-5-yl) -methanesulfonamide;! ^-Methyl-1 ^ _ (2-methyl-5-{[2- (2-remuneration-2, 3-diamino-1 ^ 1-〇 bow 11-5 -ylamino group) -5-trisgas methyl-sulfanyl d-4 -ylamino] methyl pyrimidine U-4-yl) -Methanesulfonamide; N-methyl-N- (4-methyl-6-{[2- (2 -fluorene-2,3 -dichloro-1H-D ) -5 -trifluoromethyl-pyrimidine, hydrazidine-4-ylamino] -methyl} -pyrimidineB-5-yl) -methanesulfonamide; N-methyl-N_ (5-methyl -6- {[2- (2- 嗣 -2,3-—Hydrogen-1H- 卩 D 朵 -5 -aminoamino group 5_trifluoromethyl- BB aden-4-ylamino group]- Methylpyridazine-2-yl) -methanesulfonamide; N-methyl-N-(5-methyl-3-{[2- (2-fluorene-2,3-diamine-11 ~ 1-0 lead 0 -5 -ylamino) _5 -Triple methyl-pyrimidin-4-ylamino] -methylbuxamine-2-yl) -methanesulfonylamine; N- Methyl-N- (2-methyl-6-{[2- (2-keto-2,3-dihydro-114-indole-5-ylamino) -5 -Trifluoromethyl-pyrimidin-4-ylamino] -methylbutyridin-5-yl) -methanesulfonamide; -225- 200539871 ί. ^ Π) Ν -methyl-Ν- (3-Methyl-6-{[2- (2-keto-2,3-dihydro-1H-indodol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamine Group] -methylpyrazine-2-yl) -methanesulfonamide; and N-methyl-N_ (6-methyl-5 _ {[2- (2_fluorene-2,3-dichloro-1H -D-D-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methylpyrimidin-4-yl) -methanesulfonamide. 1 1. Use of a compound according to item 1 of the patent application for the preparation of a medicament for treating abnormal cell growth in a mammal. 12. A pharmaceutical composition for treating abnormal cell growth in mammals, which comprises an effective amount of a compound for treating abnormal cell growth, such as in the scope of claim 1, and a pharmaceutically acceptable carrier. -226 - 200539871 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： Ατττ 八、本案若有化學式時，請揭示最能顯示發明特徵的化學 式··-226-200539871 7. Designated representative map: (1). The designated representative map of this case is: None. (2). Brief description of the component symbols of this representative map: Ατττ 8. If there is a chemical formula in this case, please disclose the features that can best show the invention.的 Chemical Formula ·· N…V r^CR1R\ 1N… V r ^ CR1R \ 1
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Families Citing this family (15)

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Publication number Priority date Publication date Assignee Title
WO2005118544A2 (en) * 2004-05-18 2005-12-15 Rigel Pharmaceuticals, Inc. Cycloalkyl substituted pyrimidinediamine compounds and their uses
US20070032514A1 (en) * 2005-07-01 2007-02-08 Zahn Stephan K 2,4-diamino-pyrimidines as aurora inhibitors
EA014551B1 (en) * 2005-12-21 2010-12-30 Пфайзер Продактс Инк. Pyrimidine derivatives for the treatment of abnormal cell growth
ES2593486T3 (en) * 2007-04-18 2016-12-09 Pfizer Products Inc. Sulfonyl amide derivatives for the treatment of abnormal cell growth
EP2183225A1 (en) * 2007-07-17 2010-05-12 Rigel Pharmaceuticals, Inc. Cyclic amine substituted pyrimidinediamines as pkc inhibitors
JP2011505407A (en) * 2007-12-03 2011-02-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Diaminopyridine for treating diseases characterized by excessive or abnormal cell proliferation
WO2009143389A1 (en) * 2008-05-21 2009-11-26 Ariad Pharmaceuticals, Inc. Phosphorous derivatives as kinase inhibitors
US8410126B2 (en) * 2009-05-29 2013-04-02 Boehringer Ingelheim International Gmbh Pyrimidine inhibitors of PKTK2
WO2011018517A1 (en) 2009-08-14 2011-02-17 Boehringer Ingelheim International Gmbh Regioselective preparation of 2-amino-5-trifluoromethylpyrimidine derivatives
US8933227B2 (en) 2009-08-14 2015-01-13 Boehringer Ingelheim International Gmbh Selective synthesis of functionalized pyrimidines
US20120244141A1 (en) 2010-09-28 2012-09-27 Boehringer Ingelheim International Gmbh Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors
WO2014174745A1 (en) * 2013-04-26 2014-10-30 国立大学法人京都大学 Eg5 INHIBITOR
CN109608444B (en) * 2018-11-27 2022-02-11 中国药科大学 ERK inhibitor containing isoindolinone and preparation method and use thereof
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WO2024140671A1 (en) * 2022-12-29 2024-07-04 南京昕瑞再生医药科技有限公司 Fused tricyclic derivative, pharmaceutical composition comprising same, and use thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9721437D0 (en) * 1997-10-10 1997-12-10 Glaxo Group Ltd Heteroaromatic compounds and their use in medicine
AR042586A1 (en) 2001-02-15 2005-06-29 Sugen Inc 3- (4-AMIDOPIRROL-2-ILMETILIDEN) -2-INDOLINONE AS INHIBITORS OF PROTEIN KINASE; YOUR PHARMACEUTICAL COMPOSITIONS; A METHOD FOR THE MODULATION OF THE CATALYTIC ACTIVITY OF PROTEINQUINASE; A METHOD TO TREAT OR PREVENT AN AFFECTION RELATED TO PROTEINQUINASE
WO2003030909A1 (en) * 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
UA80767C2 (en) * 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
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