CN1298709C - 用作抗肿瘤剂的噻吩和噻唑磺酰胺化合物 - Google Patents
用作抗肿瘤剂的噻吩和噻唑磺酰胺化合物 Download PDFInfo
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- CN1298709C CN1298709C CNB028212150A CN02821215A CN1298709C CN 1298709 C CN1298709 C CN 1298709C CN B028212150 A CNB028212150 A CN B028212150A CN 02821215 A CN02821215 A CN 02821215A CN 1298709 C CN1298709 C CN 1298709C
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- Prior art keywords
- sulphonamide
- compound
- alkyl
- halogen
- solution
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35201201P | 2001-10-25 | 2001-10-25 | |
| US60/352,012 | 2001-10-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1575286A CN1575286A (zh) | 2005-02-02 |
| CN1298709C true CN1298709C (zh) | 2007-02-07 |
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| CNB028212150A Expired - Fee Related CN1298709C (zh) | 2001-10-25 | 2002-10-15 | 用作抗肿瘤剂的噻吩和噻唑磺酰胺化合物 |
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Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1401825E (pt) * | 2001-06-11 | 2009-10-23 | Virochem Pharma Inc | Compostos e métodos para o tratamento ou para a prevenção de infecções com flavivírus |
| SE0102616D0 (sv) * | 2001-07-25 | 2001-07-25 | Astrazeneca Ab | Novel compounds |
| US7375131B2 (en) * | 2002-06-06 | 2008-05-20 | Smithklinebeecham Corp. | NF-κB inhibitors |
| CN100413861C (zh) | 2002-12-10 | 2008-08-27 | 维勒凯姆制药股份有限公司 | 用于治疗或预防黄病毒感染的化合物 |
| SE0300092D0 (sv) * | 2003-01-15 | 2003-01-15 | Astrazeneca Ab | Novel compounds |
| SE0300091D0 (sv) * | 2003-01-15 | 2003-01-15 | Astrazeneca Ab | Novel compounds |
| US20050085531A1 (en) * | 2003-10-03 | 2005-04-21 | Hodge Carl N. | Thiophene-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| JP5134247B2 (ja) * | 2004-09-13 | 2013-01-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スルホンアミド含有化合物の血管新生阻害物質との併用 |
| US8772269B2 (en) | 2004-09-13 | 2014-07-08 | Eisai R&D Management Co., Ltd. | Use of sulfonamide-including compounds in combination with angiogenesis inhibitors |
| WO2006030947A1 (ja) * | 2004-09-13 | 2006-03-23 | Eisai R & D Management Co., Ltd. | スルホンアミド含有化合物の血管新生阻害物質との併用 |
| WO2006090921A1 (ja) * | 2005-02-28 | 2006-08-31 | Eisai R & D Management Co., Ltd. | スルホンアミド化合物のリンパ球活性化抑制作用 |
| KR20070114774A (ko) * | 2005-02-28 | 2007-12-04 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 술폰아미드 화합물의 혈관 신생 저해 물질과의 신규 병용 |
| DE602006021401D1 (de) | 2005-02-28 | 2011-06-01 | Eisai R&D Man Co Ltd | Neue kombinierte anwendung einer sulfonamid-verbindung zur behandlung von krebs |
| NZ563909A (en) | 2005-05-13 | 2011-10-28 | Virochem Pharma Inc | Thiophene derivatives and their use for the treatment or prevention of flavivirus infections |
| US7208506B2 (en) | 2005-07-07 | 2007-04-24 | Hoffmann-La Roche Inc. | Heteroarylethenyl derivatives, their manufacture and use as pharmaceutical agents |
| US7625896B2 (en) * | 2005-11-25 | 2009-12-01 | Hoffman-La Roche Inc. | Pyridylsulfonamide derivatives |
| JPWO2007123274A1 (ja) | 2006-04-20 | 2009-09-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スルホンアミド化合物の新規感受性マーカー |
| US7939532B2 (en) * | 2006-10-26 | 2011-05-10 | Hoffmann-La Roche Inc. | Heterocyclyl pyridyl sulfonamide derivatives, their manufacture and use as pharmaceutical agents |
| CA2670260A1 (en) | 2006-11-15 | 2008-05-22 | Virochem Pharma Inc. | Thiophene analogues for the treatment or prevention of flavivirus infections |
| US7879884B2 (en) | 2007-05-16 | 2011-02-01 | Hoffmann-La Roche Inc. | Aryl pyridyl sulfonamide derivatives, their manufacture and use as pharmaceutical agents |
| CN101899008B (zh) * | 2010-05-20 | 2012-10-17 | 中国人民解放军第二军医大学 | N-取代嘧啶磺酰基-取代苯甲酰胺类化合物及其制备药物的用途 |
| CN103450149B (zh) * | 2012-06-01 | 2015-10-14 | 中国科学院上海有机化学研究所 | 苯基噻吩磺酰胺类化合物及其制备方法和用途 |
| JP6364967B2 (ja) * | 2014-05-30 | 2018-08-01 | 東ソー株式会社 | ジチエノベンゾジチオフェンの製造方法 |
| CN106588868A (zh) * | 2016-11-16 | 2017-04-26 | 武汉理工大学 | 一种2‑溴‑3‑噻吩甲酸中间体的合成方法 |
| CN108558822B (zh) * | 2018-06-01 | 2020-12-18 | 盐城锦明药业有限公司 | N-((5-溴噻吩-2-基)磺酰基)-2,4-二氯苯甲酰胺的合成方法 |
| CN110835345A (zh) * | 2018-08-17 | 2020-02-25 | 中国科学院上海药物研究所 | 一类细胞周期依赖性激酶的降解剂、其制备方法、药物组合物及其用途 |
| CN109265437A (zh) * | 2018-10-19 | 2019-01-25 | 凯莱英医药集团（天津）股份有限公司 | 一种3-羟基噻吩-2-羧酸酯类化合物的制备方法 |
| WO2024251876A1 (en) * | 2023-06-07 | 2024-12-12 | KRæFTENS BEKæMPELSE | PROTACs AND HyT-PD MOLECULES FOR TARGETED PROTEIN DEGRADATION OF DCAF15 AND THEIR USE IN THE TREATMENT OF AMYLOIDOSIS |
| WO2025031360A1 (zh) * | 2023-08-09 | 2025-02-13 | 上海科技大学 | 磺酰胺类化合物及其用途 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1058401A (zh) * | 1990-07-17 | 1992-02-05 | 伊莱利利公司 | 抗肿瘤组合物和治疗方法 |
| EP0513979A1 (en) * | 1991-03-26 | 1992-11-19 | Merck & Co. Inc. | Angiotensin II antagonists incorporating a substituted thiophene or furan |
| CN1076447A (zh) * | 1992-03-13 | 1993-09-22 | 伊莱利利公司 | 抗肿瘤组合物及治疗方法 |
| WO1998001440A2 (en) * | 1996-07-05 | 1998-01-15 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Anti-viral pharmaceutical compositions containing saturated 1,2-dithiaheterocyclic compounds and uses thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA813332B (en) * | 1980-06-21 | 1982-05-26 | Pfizer | Larvicides and isecticides |
| CA2267998A1 (en) * | 1996-10-04 | 1998-04-09 | Eli Lilly And Company | Antitumor compositions and methods of treatment |
| JP4316787B2 (ja) | 2000-01-11 | 2009-08-19 | 壽製薬株式会社 | エーテル又はアミド誘導体、その製法並びにそれを含有する糖尿病治療剤、 |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1058401A (zh) * | 1990-07-17 | 1992-02-05 | 伊莱利利公司 | 抗肿瘤组合物和治疗方法 |
| EP0513979A1 (en) * | 1991-03-26 | 1992-11-19 | Merck & Co. Inc. | Angiotensin II antagonists incorporating a substituted thiophene or furan |
| CN1076447A (zh) * | 1992-03-13 | 1993-09-22 | 伊莱利利公司 | 抗肿瘤组合物及治疗方法 |
| WO1998001440A2 (en) * | 1996-07-05 | 1998-01-15 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Anti-viral pharmaceutical compositions containing saturated 1,2-dithiaheterocyclic compounds and uses thereof |
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