EA022776B1 - Арилсульфонамиды для лечения заболеваний цнс - Google Patents
Арилсульфонамиды для лечения заболеваний цнс Download PDFInfo
- Publication number
- EA022776B1 EA022776B1 EA201390398A EA201390398A EA022776B1 EA 022776 B1 EA022776 B1 EA 022776B1 EA 201390398 A EA201390398 A EA 201390398A EA 201390398 A EA201390398 A EA 201390398A EA 022776 B1 EA022776 B1 EA 022776B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- chloro
- indol
- dihydro
- pyridin
- group
- Prior art date
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| PL39243610A PL392436A1 (pl) | 2010-09-17 | 2010-09-17 | Pochodne arylosulfonamidów do leczenia chorób odśrodkowego układu nerwowego |
| PCT/EP2011/066054 WO2012035123A1 (en) | 2010-09-17 | 2011-09-16 | Arylosulfonamides for the treatment of cns diseases |
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| EA201390398A1 EA201390398A1 (ru) | 2013-07-30 |
| EA022776B1 true EA022776B1 (ru) | 2016-02-29 |
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| WO2015158313A1 (en) | 2014-04-19 | 2015-10-22 | Sunshine Lake Pharma Co., Ltd. | Sulfonamide derivatives and pharmaceutical applications thereof |
| CN106749219A (zh) * | 2015-11-20 | 2017-05-31 | 江苏恩华药业股份有限公司 | 一种内酰胺类衍生物及其应用 |
| CN107602446B (zh) * | 2016-07-12 | 2020-04-07 | 中国科学院上海药物研究所 | 1,4-双取代-1,2,3,6-四氢吡啶类化合物、其制备方法、药物组合物及其应用 |
| PT4082616T (pt) * | 2019-12-24 | 2025-12-02 | Sumitomo Pharma Co Ltd | Derivado de amida ácida alifática |
| CN116157124A (zh) * | 2020-05-29 | 2023-05-23 | 大邱庆北尖端医疗产业振兴财团 | 磺胺衍生物和含其作为活性成分的用于预防或治疗精神疾病的药物组合物 |
| KR102447231B1 (ko) * | 2020-05-29 | 2022-09-27 | 재단법인 대구경북첨단의료산업진흥재단 | 설폰아미드 유도체 및 이를 유효성분으로 함유하는 정신질환의 예방 또는 치료용 약학적 조성물 |
Citations (2)
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| US5670511A (en) * | 1995-01-12 | 1997-09-23 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Indolepiperidine derivatives |
| EP0976732A1 (en) * | 1997-03-31 | 2000-02-02 | Eisai Co., Ltd. | 1,4-substituted cyclic amine derivatives |
Family Cites Families (9)
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| FR2258843B1 (https=) * | 1974-01-30 | 1977-09-09 | Roussel Uclaf | |
| EP0185429A1 (en) | 1984-12-21 | 1986-06-25 | Duphar International Research B.V | New bicyclic heteroaryl piperazines |
| JP2556722B2 (ja) | 1988-02-18 | 1996-11-20 | 興和株式会社 | 新規なスルホンアミド化合物 |
| GB9825413D0 (en) * | 1998-11-19 | 1999-01-13 | Lilly Co Eli | Pharmaceutical compounds |
| GB9906624D0 (en) * | 1999-03-23 | 1999-05-19 | Smithkline Beecham Plc | Novel compounds |
| MXPA05006463A (es) * | 2002-12-27 | 2005-08-26 | Lundbeck & Co As H | Derivados de 1,2,4-triaminobenceno, utiles para tratar transtornos del sistema nervioso central. |
| US7153858B2 (en) | 2003-01-31 | 2006-12-26 | Epix Delaware, Inc. | Arylpiperazinyl compounds |
| US7135575B2 (en) * | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
| CA2637531A1 (en) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-ht6 receptor affinity |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5670511A (en) * | 1995-01-12 | 1997-09-23 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Indolepiperidine derivatives |
| EP0976732A1 (en) * | 1997-03-31 | 2000-02-02 | Eisai Co., Ltd. | 1,4-substituted cyclic amine derivatives |
Non-Patent Citations (6)
| Title |
|---|
| FORBES I.T. ET AL.: "CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 10, no. 16, 21 August 2000 (2000-08-21), pages 1803-1806, XP004216003, ISSN: 0960-894X, DOI: 10.1016/S0960-894X(00)00347-4 compound 10 * |
| ISHIZUMI K. ET AL.: "SUCCINIMIDE DERIVATIVES. II.1) SYNTHESIS AND ANTIPSYCHOTIC ACTIVITY OF N- not 4- not 4-(1,2-BENZISOTHIAZOL-3-YL)-l-PIPERAZINYL 3/4 BUTYL 3/4 1,2-CIS-CYCLOHEXANEDICARBOXIMIDE (SM-9018) AND RELATED COMPOUNDS2.3)", CHEMICAL & PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOCIETY OF JAPAN, vol. 12, no. 43, 1 December 1995 (1995-12-01), pages 2139-2151, XP001026361, ISSN: 0009-2363 compound 45 * |
| LEOPOLDO M. ET AL.: "Structure-affinity relationship study on N-[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamides as potent and selective dopamine D3 receptor ligands", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 45, no. 26, 22 November 2002 (2002-11-22), pages 5727-5735, XP002256410, ISSN: 0022-2623, DOI: 10.1021/JM020952A the whole document * |
| LEOPOLDO MARCELLO ET AL.: "Design, synthesis, and binding affinities of potential positron emission tomography (PET) ligands for visualization of brain dopamine D-3 receptors", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 49, no. 1, 1 January 2006 (2006-01-01), pages 358-365, XP002465112, ISSN: 0022-2623, DOI: 10.1021/JM050734S the whole document * |
| NAVAS ET AL.: "Analogues of the potential antipsychotic agent 1192U90: amide modifications", BIOORGANIC AND MEDICINAL CHEMISTRY, vol. 6, 12 January 1998 (1998-01-12), pages 811-823, XP002662901, the whole document * |
| NORMAN ET AL.: "STRUCTURE-ACTIVITY RELATIONSHIPS OF A SERIES OF SUBSTITUTED BENZAMIDES: POTENT D2/5-HT2 ANTAGONISTS AND 5-HT1A AGONISTS AS NEUROLEPTIC AGENTS", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, no. 5, 1 March 1996 (1996-03-01), pages 1172-1178, XP002050407, ISSN: 0022-2623, DOI: 10.1021/JM950551D the whole document * |
Also Published As
| Publication number | Publication date |
|---|---|
| EA201390398A1 (ru) | 2013-07-30 |
| EP2616440A1 (en) | 2013-07-24 |
| CN104529999A (zh) | 2015-04-22 |
| NZ607031A (en) | 2014-06-27 |
| US20130172365A1 (en) | 2013-07-04 |
| KR20130143569A (ko) | 2013-12-31 |
| JP2013540738A (ja) | 2013-11-07 |
| ZA201302390B (en) | 2013-12-23 |
| JP5899218B2 (ja) | 2016-04-06 |
| US8822517B2 (en) | 2014-09-02 |
| ZA201305970B (en) | 2014-04-30 |
| AU2011303807A1 (en) | 2013-02-28 |
| AU2011303807B2 (en) | 2014-07-17 |
| US9120767B2 (en) | 2015-09-01 |
| PL392436A1 (pl) | 2012-03-26 |
| WO2012035123A1 (en) | 2012-03-22 |
| CA2808246A1 (en) | 2012-03-22 |
| BR112013006313A2 (pt) | 2016-06-07 |
| US20140336200A1 (en) | 2014-11-13 |
| UA109793C2 (uk) | 2015-10-12 |
| CN103108864A (zh) | 2013-05-15 |
| MX2013002956A (es) | 2013-05-09 |
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