JP2010504352A - バソプレッシン拮抗薬としてのスピロベンズアゼピン類 - Google Patents
バソプレッシン拮抗薬としてのスピロベンズアゼピン類 Download PDFInfo
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- JP2010504352A JP2010504352A JP2009529371A JP2009529371A JP2010504352A JP 2010504352 A JP2010504352 A JP 2010504352A JP 2009529371 A JP2009529371 A JP 2009529371A JP 2009529371 A JP2009529371 A JP 2009529371A JP 2010504352 A JP2010504352 A JP 2010504352A
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- Prior art keywords
- benzazepine
- phenyl
- carbonyl
- dihydro
- oxospiro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
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- Emergency Medicine (AREA)
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- Pregnancy & Childbirth (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82667106P | 2006-09-22 | 2006-09-22 | |
| PCT/US2007/078926 WO2008036759A1 (en) | 2006-09-22 | 2007-09-19 | Spiro benzazepines as vasopressin antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010504352A true JP2010504352A (ja) | 2010-02-12 |
| JP2010504352A5 JP2010504352A5 (enExample) | 2010-12-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009529371A Pending JP2010504352A (ja) | 2006-09-22 | 2007-09-19 | バソプレッシン拮抗薬としてのスピロベンズアゼピン類 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7825111B2 (enExample) |
| EP (1) | EP2076517A1 (enExample) |
| JP (1) | JP2010504352A (enExample) |
| CN (1) | CN101541807A (enExample) |
| AU (1) | AU2007299822A1 (enExample) |
| CA (1) | CA2665851A1 (enExample) |
| WO (1) | WO2008036759A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014104209A1 (ja) * | 2012-12-26 | 2014-07-03 | 株式会社 三和化学研究所 | 新規ベンゾアゼピン誘導体及びその医薬用途 |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7119083B2 (en) * | 2001-10-12 | 2006-10-10 | Azevan Pharmaceuticals, Inc. | β-Lactamyl vasopressin V1a Antagonists |
| CA2601709C (en) | 2005-03-22 | 2017-02-14 | Azevan Pharmaceuticals, Inc. | Beta-lactamylalkanoic acids |
| AR066834A1 (es) * | 2007-06-06 | 2009-09-16 | Janssen Pharmaceutica Nv | Espirobenzoazepanos como antagonistas de vasopresina, composiciones farmaceuticas que los contienen, proceso de preparacion y usos para el tratamiento de afecciones cardiacas, renales y del sistema nervioso central. |
| RU2623209C9 (ru) | 2010-07-01 | 2018-01-22 | Азеван Фармасьютикалз, Инк. | Способы лечения посттравматического стрессового расстройства |
| TW201600522A (zh) * | 2014-02-20 | 2016-01-01 | 赫孚孟拉羅股份公司 | 螺－唑酮 |
| FI3122743T3 (fi) | 2014-03-28 | 2023-03-02 | Azevan Pharmaceuticals Inc | Koostumuksia ja menetelmiä hermostoa rappeuttavien sairauksien hoitamiseksi |
| WO2019050988A1 (en) * | 2017-09-05 | 2019-03-14 | Blackthorn Therapeutics, Inc. | ANTAGONISTS OF THE VASOPRESSIN RECEPTOR, PRODUCTS AND RELATED METHODS |
| BR112020005107A2 (pt) | 2017-09-15 | 2020-11-03 | Azevan Pharmaceuticals, Inc. | composições e métodos para o tratamento de lesão cerebral |
| WO2019141575A1 (de) | 2018-01-16 | 2019-07-25 | Bayer Aktiengesellschaft | Unterstützung bei der behandlung von herzinsuffizienz |
| CN109608411A (zh) * | 2018-12-17 | 2019-04-12 | 上海合全药物研发有限公司 | 一种叔丁基-1-氧亚基-6-氧杂-9-氮杂螺[4.5]癸烷-9-甲酸基酯的制法 |
| TW202220958A (zh) * | 2020-08-07 | 2022-06-01 | 美商卡司馬療法公司 | Ｔｒｐｍｌ調節劑 |
| CN112939864B (zh) * | 2021-01-29 | 2022-05-06 | 中国医科大学 | 螺[苯并[c]氮杂-1,1’-环己基]-3-酮类化合物 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04154765A (ja) * | 1989-10-20 | 1992-05-27 | Otsuka Pharmaceut Co Ltd | ベンゾヘテロ環化合物 |
| JPH04321669A (ja) * | 1991-04-19 | 1992-11-11 | Otsuka Pharmaceut Co Ltd | バソプレシン拮抗剤 |
| JPH06507182A (ja) * | 1992-01-30 | 1994-08-11 | エルフ・サノフィ | Ｎ−スルホニル−２−オキソインドール誘導体、それらの製造、及びそれらが存在する薬学的組成物 |
| JPH07224034A (ja) * | 1993-07-30 | 1995-08-22 | Sanofi Sa | １−ベンジル−１，３−ジヒドロインドール−２−オン誘導体、その製造方法、およびそれを含む薬理組成物 |
| JPH07247269A (ja) * | 1993-07-30 | 1995-09-26 | Sanofi Sa | １−ベンゼンスルホニル−１，３−ジヒドロ−インドール−２−オン誘導体、それらの調製およびそれらが含まれる医薬組成物 |
| US20020128208A1 (en) * | 2000-12-15 | 2002-09-12 | Snyder James P. | Nonpeptide agonists and antagonists of vasopressin receptors |
| JP2004502677A (ja) * | 2000-07-05 | 2004-01-29 | オーソーマクニール ファーマシューティカル， インコーポレイテッド | バソプレシン拮抗質としての非ペプチド系置換スピロベンゾアゼピン |
| WO2005000819A1 (en) * | 2003-06-17 | 2005-01-06 | Janssen Pharmaceutica N.V. | Process for the preparation of nonpeptide substituted spirobenzoazepine derivatives |
| WO2005037795A2 (en) * | 2003-06-17 | 2005-04-28 | Janssen Pharmaceutica N.V. | Substituted spirobenzazepines |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4617302A (en) | 1984-10-15 | 1986-10-14 | Eli Lilly And Company | Inotropic agents |
| US5985869A (en) | 1989-10-20 | 1999-11-16 | Otsuka Pharmaceutical Company, Limited | Benzoheterocyclic compounds |
| US5258510A (en) | 1989-10-20 | 1993-11-02 | Otsuka Pharma Co Ltd | Benzoheterocyclic compounds |
| US5849780A (en) | 1992-01-30 | 1998-12-15 | Sanofi | 1-benzenesulfonyl-1-1,3-dihydroindol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| US5663431A (en) | 1992-01-30 | 1997-09-02 | Sanofi | 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| US5686624A (en) | 1992-01-30 | 1997-11-11 | Sanofi | 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
| AU5292393A (en) | 1992-10-07 | 1994-04-26 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
| US5512563A (en) | 1993-07-29 | 1996-04-30 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5464788A (en) | 1994-03-24 | 1995-11-07 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
| US5753648A (en) | 1995-01-17 | 1998-05-19 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| AUPP150098A0 (en) | 1998-01-27 | 1998-02-19 | Fujisawa Pharmaceutical Co., Ltd. | Benzamide derivatives |
| US7011898B2 (en) * | 2003-03-21 | 2006-03-14 | Air Products And Chemicals, Inc. | Method of joining ITM materials using a partially or fully-transient liquid phase |
| EP1984342A2 (en) | 2006-01-20 | 2008-10-29 | Janssen Pharmaceutica, N.V. | Novel solid forms of (4r)-1-[4-(2-chloro-5-fluorobenzoyl)amino-3-methoxybenzoyl]-1,2,3,5-tetrahydro-spiro[4h-1-benzazepine-4,1'-[2]cyclopentene]-3'-carboxylic acid |
-
2007
- 2007-09-19 CA CA002665851A patent/CA2665851A1/en not_active Abandoned
- 2007-09-19 JP JP2009529371A patent/JP2010504352A/ja active Pending
- 2007-09-19 US US11/857,954 patent/US7825111B2/en not_active Expired - Fee Related
- 2007-09-19 WO PCT/US2007/078926 patent/WO2008036759A1/en not_active Ceased
- 2007-09-19 AU AU2007299822A patent/AU2007299822A1/en not_active Abandoned
- 2007-09-19 CN CNA2007800432304A patent/CN101541807A/zh active Pending
- 2007-09-19 EP EP07842807A patent/EP2076517A1/en not_active Withdrawn
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04154765A (ja) * | 1989-10-20 | 1992-05-27 | Otsuka Pharmaceut Co Ltd | ベンゾヘテロ環化合物 |
| JPH04321669A (ja) * | 1991-04-19 | 1992-11-11 | Otsuka Pharmaceut Co Ltd | バソプレシン拮抗剤 |
| JPH06507182A (ja) * | 1992-01-30 | 1994-08-11 | エルフ・サノフィ | Ｎ−スルホニル−２−オキソインドール誘導体、それらの製造、及びそれらが存在する薬学的組成物 |
| JPH07224034A (ja) * | 1993-07-30 | 1995-08-22 | Sanofi Sa | １−ベンジル−１，３−ジヒドロインドール−２−オン誘導体、その製造方法、およびそれを含む薬理組成物 |
| JPH07247269A (ja) * | 1993-07-30 | 1995-09-26 | Sanofi Sa | １−ベンゼンスルホニル−１，３−ジヒドロ−インドール−２−オン誘導体、それらの調製およびそれらが含まれる医薬組成物 |
| JP2004502677A (ja) * | 2000-07-05 | 2004-01-29 | オーソーマクニール ファーマシューティカル， インコーポレイテッド | バソプレシン拮抗質としての非ペプチド系置換スピロベンゾアゼピン |
| US20020128208A1 (en) * | 2000-12-15 | 2002-09-12 | Snyder James P. | Nonpeptide agonists and antagonists of vasopressin receptors |
| WO2005000819A1 (en) * | 2003-06-17 | 2005-01-06 | Janssen Pharmaceutica N.V. | Process for the preparation of nonpeptide substituted spirobenzoazepine derivatives |
| WO2005037795A2 (en) * | 2003-06-17 | 2005-04-28 | Janssen Pharmaceutica N.V. | Substituted spirobenzazepines |
Non-Patent Citations (2)
| Title |
|---|
| JPN6012068639; ＸＩＡＮＧ，Ｍ．Ａ． ｅｔ ａｌ: 'Ｓｙｎｔｈｅｓｉｓ ａｎｄ ｅｖａｌｕａｔｉｏｎ ｏｆ ｎｏｎｐｅｐｔｉｄｅ ｓｕｂｓｔｉｔｕｔｅｄ ｓｐｉｒｏｂｅｎｚａｚｅｐｉｎｅｓ ａｓ ｐｏｔｅｎｔ ｖａｓｏｐｒｅｓｓｉｎ ａｎｔａｇｏｎｉｓ' Ｂｉｏｏｒｇ Ｍｅｄ Ｃｈｅｍ Ｌｅｔｔ Ｖｏｌ．１４， Ｎｏ．１２, 2004, ｐ．３１４３-６ * |
| JPN6012068640; ＸＩＡＮＧ，Ｍ．Ａ． ｅｔ ａｌ: 'Ｓｙｎｔｈｅｓｉｓ ａｎｄ ｅｖａｌｕａｔｉｏｎ ｏｆ ｓｐｉｒｏｂｅｎｚａｚｅｐｉｎｅｓ ａｓ ｐｏｔｅｎｔ ｖａｓｏｐｒｅｓｓｉｎ ｒｅｃｅｐｔｏｒ ａｎｔａｇｏｎｉｓｔｓ' Ｂｉｏｏｒｇ Ｍｅｄ Ｃｈｅｍ Ｌｅｔｔ Ｖｏｌ．１４， Ｎｏ．１１, 2004, ｐ．２９８７-９ * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014104209A1 (ja) * | 2012-12-26 | 2014-07-03 | 株式会社 三和化学研究所 | 新規ベンゾアゼピン誘導体及びその医薬用途 |
| KR20150098614A (ko) * | 2012-12-26 | 2015-08-28 | 가부시키가이샤산와카가쿠켄큐쇼 | 신규 벤조아제핀 유도체 및 그 의약 용도 |
| JP5968466B2 (ja) * | 2012-12-26 | 2016-08-10 | 株式会社三和化学研究所 | 新規ベンゾアゼピン誘導体及びその医薬用途 |
| JP2016199575A (ja) * | 2012-12-26 | 2016-12-01 | 株式会社三和化学研究所 | 新規ベンゾアゼピン誘導体及びその医薬用途 |
| US9586905B2 (en) | 2012-12-26 | 2017-03-07 | Sanwa Kagaku Kenkyusho Co., Ltd. | Benzoazepine derivative and medical use thereof |
| KR101983880B1 (ko) | 2012-12-26 | 2019-05-29 | 가부시키가이샤산와카가쿠켄큐쇼 | 신규 벤조아제핀 유도체 및 그 의약 용도 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2076517A1 (en) | 2009-07-08 |
| US7825111B2 (en) | 2010-11-02 |
| WO2008036759A1 (en) | 2008-03-27 |
| AU2007299822A1 (en) | 2008-03-27 |
| US20080076754A1 (en) | 2008-03-27 |
| CA2665851A1 (en) | 2008-03-27 |
| CN101541807A (zh) | 2009-09-23 |
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