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WO2007036131A1 - Dérivés de carzole sulfamide et leur procédé de préparation - Google Patents

Dérivés de carzole sulfamide et leur procédé de préparation Download PDF

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Publication number
WO2007036131A1
WO2007036131A1 PCT/CN2006/002298 CN2006002298W WO2007036131A1 WO 2007036131 A1 WO2007036131 A1 WO 2007036131A1 CN 2006002298 W CN2006002298 W CN 2006002298W WO 2007036131 A1 WO2007036131 A1 WO 2007036131A1
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WIPO (PCT)
Prior art keywords
sulfonamide
group
substituted
carbazole
ethylcarbazole
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Ceased
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PCT/CN2006/002298
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English (en)
Chinese (zh)
Inventor
Laixing Hu
David W. Boykin
Zhuorong Li
Jiandong Jiang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Medicinal Biotechnology of CAMS and PUMC
Georgia State University Research Foundation Inc
Original Assignee
Institute of Medicinal Biotechnology of CAMS and PUMC
Georgia State University Research Foundation Inc
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Filing date
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Publication of WO2007036131A1 publication Critical patent/WO2007036131A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a novel carbazole sulfonamide derivative and a process for the preparation thereof, and to a pharmaceutical composition containing the carbazole sulfonamide derivative as an active ingredient.
  • Anti-mitotic agents are a class of potent anti-tumor drugs that block tumor cells in mitosis (M) and induce apoptosis, causing tumor atrophy or necrosis.
  • Traditional anti-mitotic agents mainly tubulin inhibitors, such as paclitaxel and vinblastine antitumor drugs, can inhibit the polymerization or depolymerization of microtubules and mitosis of tumor cells by combining with specific sites of tubulin. In the process, the spindle is difficult to form, the cell cycle is blocked in the M phase, and the apoptosis of the tumor cells is further induced (Li Jianong, Jiang Jiandong, Journal of Pharmaceutical Sciences, (2003), 38 (4), 311-315).
  • the main object of the present invention is to screen and synthesize a new class of small molecule anti-mitotic agents by studying the structure-activity of heterocyclic sulfonamide derivatives: carbazole sulfonamide derivatives and pharmaceutically acceptable salts, which can not only tumors
  • the cell is blocked in the mitosis (M) phase, and also has significant antitumor activity, and has the advantages of small molecular weight, simple synthesis, and small toxic side effects.
  • the invention also provides a process for the preparation of the oxazole sulfonamide derivative.
  • the present invention also provides a pharmaceutical composition containing such an oxazole sulfonamide derivative as an active ingredient.
  • a further object of the present invention is to provide an anti-tumor application of the carbazole sulfonamide derivative and a pharmaceutically acceptable salt thereof, which can be used as an anti-mitotic agent, especially in the treatment of solid tumors, including with other anti-tumor Chemotherapy drugs Combined with radiotherapy and the like.
  • the present invention first provides an oxazole sulfonamide derivative having the following general formula (I) and a pharmaceutically acceptable salt -
  • R 2 represents: hydrogen, lower sulfhydryl
  • X represents: S0 2 NR 3 or NR 3 S0 2 , or a salt thereof, wherein R 3 represents:
  • R 1 represents a lower sulfhydryl group, or a different amine-substituted lower alkyl group represented by the formula (III) or a salt thereof;
  • n in the above formula (III) is 1-6;
  • R 2 and R 3 respectively represent the same or different groups: hydrogen, lower fluorenyl, hydroxyalkyl, aminoalkyl; or R 2 , R 3 Linked together by nitrogen to form a 5-7 membered cyclic amine group, such as pyrrolyl, piperidinyl, piperazinyl, morpholinyl, etc., or a salt thereof;
  • the substituent may be one or more lower alkyl, lower cyclodecyl, lower decyloxy, lower sulfonylthio, hydroxy, decyl, amino, substituted amino (eg, mono- or di-substituted) a substituent such as an amide group, an ester group, a nitro group, a cyano group, a halogen or a halogenated alkyl group;
  • Pyridyl or substituted pyridyl the substituent of which may be one or more lower alkyl, lower cyclodecyl, lower decyloxy, lower sulfonylthio, hydroxy, decyl, amino, substituted amino (eg, monosubstituted or Disubstituted), amide group, ester group, nitro group, cyano group, halogen, etc.;
  • a pyrimidinyl or substituted pyrimidinyl group the substituent of which may be one or more lower alkyl, lower cycloalkyl, lower alkoxy, lower alkylthio, hydroxy, decyl, amino, substituted amino (eg, monosubstituted or Disubstituted), amide Base, ester group, nitro group, cyano group, halogen, etc.; or,
  • “Lower sulfhydryl” especially refers to a straight or branched fluorenyl or cycloalkyl group having from 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, allyl, ring Propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, n-pentyl, isopentyl, cyclopentyl, n-hexyl, isohexyl, cyclohexyl and the like.
  • a methyl group, an ethyl group, a n-propyl group, an isopropyl group or the like is preferable.
  • “Lower decyloxy” means a methoxy group having from 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec. Butoxy, tert-butoxy, n-pentyloxy, isopentyloxy, n-hexyloxy, isohexyloxy and the like.
  • Aryloxy means phenyloxy, tolyloxy, xylyloxy and the like.
  • “Lower alkylthio” refers to an alkylthio group having from 1 to 6 carbon atoms, such as methylthio, ethylthio, n-propylthio, isopropylthio, cyclopropylthio, n-butylthio, Isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, isopentylthio, n-hexylthio, isohexylthio, etc.;
  • Arylthio means phenylthio, tolylthio, xylylthio and the like.
  • “Amido” may be methyl amide, ethyl amide, n-propyl amide, isopropyl amide, allyl amide, cyclopropyl amide, n-butyl amide, isobutyl amide A group, a n-pentylamide group, a n-hexylamide group, a phenylamide group, a tolylamide group and the like.
  • Preferred compounds according to the invention are selected from the group consisting of hydrogen, nitro, amino or amide groups, lower fluorenyl groups or lower decyloxy groups.
  • Preferred compounds according to the invention may be lower sulfhydryl groups, especially methyl, ethyl, propyl or isopropyl groups and the like.
  • the carbazole sulfonamide derivative (I) proposed by the present invention comprises an oxazole sulfonamide and a carbazole-substituted aromatic heterocyclic sulfonamide and derivatives thereof, and X in the general structure is preferably 30 2 3 or ⁇ 0 2 Or a hydrochloride salt thereof, wherein R 3 may be hydrogen or a lower alkanoyl group or a lower amino group substituted lower decanoyl group, and specific examples of X may be: S0 2 NH, NHS0 2 , S0 2 NC0CH 2 NMe 2 , S0 2 NCOCH 2 NHMe, S0 2 NC0CH 2 CH 2 NMe 2 , S0 2 NCOCH 2 CH 2 NHMe, S0 2 NC0CH 2 NEt 2 , S0 2 NCOCH 2 NHEt , or a hydrochloride thereof.
  • the substituent may be a lower alkyl group, a lower cycloalkyl group, a lower alkoxy group, a lower alkylthio group, a hydroxyl group, a decyl group, an amino group, a mono- or di- or di- a substituent such as a substituted amino group, an amide group, an ester group, a nitro group, a cyano group, a halogen or a trifluoroalkyl group; wherein Ar is a pyridyl group or a substituted pyridyl group, It is preferably 3-pyridyl.
  • Ar may also be another aromatic heterocyclic ring such as thiophene, benzothiophene, benzothiazole, naphthalene or carbazole.
  • Ar in the compound may be a substituted phenyl, pyridyl or pyrimidinyl group
  • the substituent is selected from the group consisting of lower alkyl, lower cyclodecyl, lower alkoxy, hydroxy, amino, monosubstituted or disubstituted amino , amide group, ester group, nitro group, cyano group, halogen or trifluoromethyl group.
  • Ar may be 3-alkyloxyphenyl, 5-alkoxyphenyl, di- or tri-methoxyphenyl, chloro-alkoxyphenyl, cyanophenyl or alkoxypyridyl Wait.
  • Ar may be a phenylthio group, a tolylthio group, a chlorophenyl group, a fluorophenyl group, an aminophenyl group, a cyanophenyl group, a carbamoylphenyl group, a dimethoxyphenyl group, Trimethoxyphenyl, monoethoxyphenyl, diethoxyphenyl, triethoxyphenyl, 4-isopropoxyphenyl, 4-butoxyphenyl, 4-phenoxybenzene , 3, 4-methylenedioxyphenyl, trifluoromethylphenyl, aminomethoxyphenyl, methoxychlorophenyl, naphthyl, 2-pyridyl, 3-pyridyl, 4 -pyridyl, 2-methoxy-3-pyridyl, 4-methoxy-3-pyridyl, 2,4-dimethoxy-3-pyridyl, 4-chloro-2-pyridyl
  • Ar is a dimethoxyphenyl group, a trimethoxyphenyl group, a methoxychlorophenyl group, a methoxypyridyl group, a halogenated pyridyl group or the like.
  • the carbazole sulfonamide derivative of the formula (I) according to the invention as defined above also includes a product which undergoes a salt-forming reaction with an acid.
  • the salt of the compound (I) with an acid may be inorganic acids such as hydrochloride, hydrobromide and sulfate; and organic acid salts such as acetate, lactate, succinate, and fumarate. , maleate, citrate, benzoate, methanesulfonate and p-benzoate.
  • the present invention is a carbazole sulfonamide derivative as defined in the screening of a large number of candidate compounds, non-limiting examples of which may be -
  • M mitosis
  • pharmacological experiments have shown that these compounds not only block tumor cells in mitosis (M) phase, but also have strong ability to kill various tumor cells;
  • In vivo studies of animal models of breast cancer and liver cancer have been shown to significantly inhibit the growth of malignant tumors without significant toxic side effects.
  • Particularly preferred compounds may include -
  • the present invention further provides the use of the carbazole sulfonamide derivative or a salt thereof as an anti-mitotic agent, and in the preparation of an antitumor drug.
  • an antitumor pharmaceutical composition comprising a therapeutically effective amount of the above-mentioned carbazole sulfonamide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable pharmaceutical excipient, which may be the compound itself or Mixtures with pharmaceutically acceptable excipients, diluents and the like are administered orally in the form of tablets, capsules, granules, powders or syrups or parenterally in the form of injections.
  • compositions can be prepared by conventional pharmaceutical methods.
  • useful pharmaceutical adjuvants include excipients (e.g., saccharide derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, dextrin, and carboxymethyl starch; Cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose; gum arabic; dextran; silicate derivatives such as magnesium metasilicate Aluminum; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate, etc., binders (eg gelatin, polyvinylpyrrolidone and polyethylene glycol), disintegration Agents (such as cellulose derivatives such as sodium carboxymethylcellulose, polyvinylpyrrolidone), lubricants (such as talc, calcium,
  • the carbazole sulfonamide compound of the present invention or a derivative thereof and a pharmaceutically acceptable salt can be obtained by any known method, but it is preferably obtained by reacting a sulfonyl chloride compound of a suitable structure with an amino compound.
  • the starting materials and reactants can be determined according to the structural design of X in the target compound, for example, the carbazole sulfonamide is prepared by sulfonamidation reaction between various substituted carbazole sulfonamides and arylamines.
  • Method 1 or a sulfonamidation reaction between various substituted aminocarbazoles and an aromatic ring sulfonyl chloride to prepare a carbazole-substituted aromatic cyclic sulfonamide (Method 2 below).
  • the specific process can be:
  • the obtained carbazole sulfonamide (IV) can be used as it is, or in a tetrahydrofuran (THF) solvent, and in a basic substance such as dimethylaminopyridine (DMAP), diisopropylethylamine (i-).
  • DMAP dimethylaminopyridine
  • i- diisopropylethylamine
  • the pharmaceutically acceptable salt (V) is further prepared by reacting with a suitable decanoyl chloride (R'COCl) under the catalysis of Pr 2 NEt).
  • reaction process can be illustrated by the following process:
  • the preparation of the carbazole-substituted aromatic heterocyclic sulfonamide (VII) can be carried out by reacting various substituted 9-aminocarbazoles (VI) prepared by various known methods with various suitable aromatic heterocyclic sulfonyl chlorides.
  • the specific preparation conditions were the same as those of the aforementioned carbazole sulfonamide.
  • a pharmaceutically acceptable salt of the sulfonamide (VIII) can be obtained by the same method as the above compound (V).
  • Molt-3 ⁇ cell lymphoma 0. 008 0. 009 0. 008 0. 03 0. 02 0. 02
  • PC-3 prostate cancer 0. 09 0. 25 0. 05 0. 04 0. 06 0. 32
  • mice Ten human nude mice (male, 6-7 weeks old, weighing 16-20 g) were treated with liver cancer BEL-7402, subcutaneous subcutaneous transplantation 4 mm 3 /only, and were randomly divided into control group and treatment group after 7 days. Each of the 5 rats was given a solvent every other day, and the treatment group was administered every other day (ip).
  • the tumor volume was measured weekly until it exceeded 2000 mm 3 and the experiment was terminated.
  • Tumor volume length and width 2 X 0. 52.
  • the tumor growth inhibition rate of the drug-administered group and the control group was calculated according to the following formula:
  • T mean tumor volume in the drug-administered group - mean tumor volume before administration
  • Example 1 N-(3,4-Dimethoxyphenyl)-9-ethylcarbazole-3-sulfonamide (42)
  • the product was obtained as a light brown solid. Yield: 74%; mp 182 - 184.
  • l 3 C should be ⁇ SO- c 6 ) ; ⁇ 152.9, 141.3, 140.3, 134.2, 133, 8, 129.3, 127.0, 124.2, 121.7, 121.5, 120.8, 120.5, 120.0, 109.8, 109.6, 97.4, 60.0, 55.7, 37.3, 13.6.
  • This compound was obtained in the same manner as in Example 1 from 3,4,5-trimethoxyaniline and previously synthesized 9-methylcarbazole-3-sulfonyl chloride.
  • the synthesis of 9-methylcarbazole-3-sulfonyl chloride is described in Mitsumori, Susumu; Tsuri, Tatsuo; Honma, Tsunetoshi; et al, Journal of Medicinal Chemistry (2003), 46(12), 2436-2445.
  • the product was a white solid, yield: 65%; mp 206 - 208.
  • the compound of interest is prepared from 3,4,5-trimethoxyaniline and previously prepared 9-oxazole-3-sulfonyl chloride.
  • the synthesis of 9 ⁇ -carbazole-3-sulfonyl chloride is referred to Mitsumori, Susumu; Tsuri, Tatsuo; Honma, Tsunetoshi; et al, Journal of Medicinal Chemistry (2003), 46(12), 2436-2445.
  • the product was a brown solid, yield: 75%; mp 185-187.
  • the product was a brown solid, yield: 72%; mp 222 - 224.
  • the product was a white solid, yield: 45%.
  • the product was a brown solid, yield: 56%; mp 188 - 190.
  • the product was a pale white solid, yield: 67%; mp 218 - 220.
  • the product was a white solid, yield: 70%; mp 209 - 21 ⁇ .
  • Example 1 The 3,4-dimethoxyaniline of Example 1 was replaced with 4-fluoroaniline as a light brown solid. Yield: 95%; mp 158 - 160.
  • Example 20 N-(2,4-dimethoxypyridin-3-substituted)-9-methylcarbazole-3-sulfonamide (105) The procedure was the same as Example 18 : 80%; rap 170- 172 °C.
  • the product was a white solid, yield: 65%; mp 201 - 203.
  • the product was obtained as a white solid. Yield: 82%; mp 230-232.
  • This compound was prepared from 4-methoxy-3-nitroaniline (see Rubenstein, Steven M.; Baichwal,
  • the product was a yellow solid, yield: 71%; mp 218 - 220.
  • the product was a brown solid, yield: 76%; mp 255-257.
  • the product was a white solid, yield: 80%; mp 216 - 218.
  • the product was obtained as a white solid. Yield: 67%; mp 223 - 225.
  • Example 35 ⁇ -(9-Methylcarbazole-3-substituted)-4-methoxybenzenesulfonamide (84)
  • the product was a brown solid, yield: 64%; mp 154 - 156.
  • the product was a yellow solid, yield: 78%; mp 131 - 133.
  • the product was a brown foamy solid, yield: 70%.
  • the product was obtained as a light brown solid. Yield: 77%; mp 168 169.
  • the product was obtained as a white solid. Yield: 71%; mp 198-200 s.
  • 13 C wake up R (DMS0- o0; ⁇ 159.7, 147.2, 139.9, 137.0, 135.9' 129.1, 126.0, 123, 4, 122.1, 121.6, 121.0, 120.3, 118.7, 113.9, 109.4, 109.2, 105.9, 65.7, 44.3, 36.9, 13.7.
  • the product was a brown solid, yield: 87%; mp 186 188.
  • the product was a brown solid, yield: 58%; mp 186 - 188.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Indole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des dérivés de carzole sulfamide ainsi que leurs sels pharmaceutiquement acceptables de formule (I). Ces composés peuvent être utilisés comme agents anti-mitotiques de faible poids moléculaire. Ces composés peuvent non seulement inhiber les cellules tumorales lors de la première mitose, mais possèdent également une remarquable activité antitumorale. Ils ont pour avantage de présenter un faible poids moléculaire et une synthèse simple, et ne sont pas associés à des problèmes de pharmacorésistance. Cette invention concerne aussi une composition pharmaceutique contenant comme principe actif les dérivés de carzole sulfamide.
PCT/CN2006/002298 2005-09-28 2006-09-06 Dérivés de carzole sulfamide et leur procédé de préparation Ceased WO2007036131A1 (fr)

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CN200510105255A CN1807413B (zh) 2005-09-28 2005-09-28 咔唑磺酰胺衍生物及其制备方法
CN200510105255.5 2005-09-28

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2484666A1 (fr) * 2008-08-15 2012-08-08 Georgetown University Régulateurs fluorescents d'expression de RASSF1A et prolifération des cellules cancéreuses humaines
US11053255B2 (en) 2015-06-22 2021-07-06 Georgetown University Synthesis of mahanine and related compounds

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CN100586932C (zh) * 2007-01-26 2010-02-03 中国医学科学院医药生物技术研究所 抗肿瘤化合物及其制备方法
CN101234112B (zh) * 2008-03-03 2010-10-13 中国科学院化学研究所 阳离子咔唑类化合物的制药用途
CN102068415B (zh) * 2010-12-28 2012-02-22 山西普德药业股份有限公司 一种咔唑磺酰胺类抗肿瘤药物分散片及其制备方法
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CN105906665B (zh) * 2016-05-16 2017-11-28 中国医学科学院医药生物技术研究所 咔唑磺酰胺衍生物前药或其可药用盐及其制备方法和应用
CN105949174B (zh) * 2016-05-16 2018-12-21 中国医学科学院医药生物技术研究所 咔唑磺酰胺衍生物或其药用盐及其制备方法和应用
CN107382967B (zh) * 2016-05-16 2021-02-19 中国医学科学院医药生物技术研究所 咔唑磺酰胺衍生物或其可药用盐及其制备方法和应用
CN110467598B (zh) * 2018-05-11 2021-04-13 中国医学科学院医药生物技术研究所 一种咔唑磺酰胺衍生物前药或其可药用盐及其制备方法和应用
CN109851550A (zh) * 2019-04-02 2019-06-07 中国医学科学院医药生物技术研究所 7-氨基咔唑磺酰胺衍生物及其制备方法和应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11106337A (ja) * 1997-09-30 1999-04-20 Bayer Yakuhin Ltd 乾癬の処置剤
CN1333698A (zh) * 1998-12-22 2002-01-30 沃尼尔·朗伯公司 联合化学疗法
US6399631B1 (en) * 1999-07-23 2002-06-04 Pfizer Inc. Carbazole neuropeptide Y5 antagonists
US6713473B1 (en) * 1999-04-20 2004-03-30 Meiji Seika Kaisha, Ltd. Tricyclic compounds
US6800655B2 (en) * 2002-08-20 2004-10-05 Sri International Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11106337A (ja) * 1997-09-30 1999-04-20 Bayer Yakuhin Ltd 乾癬の処置剤
CN1333698A (zh) * 1998-12-22 2002-01-30 沃尼尔·朗伯公司 联合化学疗法
US6713473B1 (en) * 1999-04-20 2004-03-30 Meiji Seika Kaisha, Ltd. Tricyclic compounds
US6399631B1 (en) * 1999-07-23 2002-06-04 Pfizer Inc. Carbazole neuropeptide Y5 antagonists
US6800655B2 (en) * 2002-08-20 2004-10-05 Sri International Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2484666A1 (fr) * 2008-08-15 2012-08-08 Georgetown University Régulateurs fluorescents d'expression de RASSF1A et prolifération des cellules cancéreuses humaines
US10457639B2 (en) 2008-08-15 2019-10-29 Georgetown University Fluorescent regulators of RASSF1A expression and human cancer cell proliferation
US11053255B2 (en) 2015-06-22 2021-07-06 Georgetown University Synthesis of mahanine and related compounds

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CN1807413B (zh) 2010-05-05

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