JP2006508970A - イミダゾ［１，５ａ］ピリジン誘導体およびアルデステロンにより仲介される疾患の処置方法 - Google Patents
イミダゾ［１，５ａ］ピリジン誘導体およびアルデステロンにより仲介される疾患の処置方法 Download PDFInfo
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- JP2006508970A JP2006508970A JP2004552632A JP2004552632A JP2006508970A JP 2006508970 A JP2006508970 A JP 2006508970A JP 2004552632 A JP2004552632 A JP 2004552632A JP 2004552632 A JP2004552632 A JP 2004552632A JP 2006508970 A JP2006508970 A JP 2006508970A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42732502P | 2002-11-18 | 2002-11-18 | |
| PCT/EP2003/012851 WO2004046145A1 (en) | 2002-11-18 | 2003-11-17 | Imidazo[1, 5a]pyridine derivatives and methods for treating aldosterone mediated diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006508970A true JP2006508970A (ja) | 2006-03-16 |
| JP2006508970A5 JP2006508970A5 (https=) | 2006-12-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2004552632A Pending JP2006508970A (ja) | 2002-11-18 | 2003-11-17 | イミダゾ［１，５ａ］ピリジン誘導体およびアルデステロンにより仲介される疾患の処置方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7223866B2 (https=) |
| EP (1) | EP1565463B1 (https=) |
| JP (1) | JP2006508970A (https=) |
| CN (1) | CN100447142C (https=) |
| AT (1) | ATE398124T1 (https=) |
| AU (1) | AU2003292039A1 (https=) |
| BR (1) | BR0316306A (https=) |
| CA (1) | CA2505752A1 (https=) |
| DE (1) | DE60321593D1 (https=) |
| ES (1) | ES2305520T3 (https=) |
| PT (1) | PT1565463E (https=) |
| WO (1) | WO2004046145A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010520869A (ja) * | 2007-03-09 | 2010-06-17 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのイミダゾ［１，５−ａ］ピリジン誘導体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DK1569896T3 (da) * | 2002-12-06 | 2007-12-10 | Xention Ltd | Tetrahydronaphthalenderivater |
| AU2003288200A1 (en) | 2002-12-09 | 2004-06-30 | Bayer Healthcare Ag | Tetrahydro-naphthalene derivatives as vanilloid receptor antagonists |
| WO2006092430A1 (de) * | 2005-03-03 | 2006-09-08 | Universität des Saarlandes | Selektive hemmstoffe humaner corticoidsynthasen |
| TW200716636A (en) | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| TW200716634A (en) * | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| TW200716105A (en) * | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Imidazole compounds |
| GT200600381A (es) * | 2005-08-25 | 2007-03-28 | Compuestos organicos | |
| EP1842543A1 (en) | 2006-04-05 | 2007-10-10 | Speedel Pharma AG | Pharmaceutical composition coprising an aldosterone synthase inhibitor and a mineralcorticoid receptor antagonist |
| WO2009058944A2 (en) | 2007-11-01 | 2009-05-07 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and /or nf- kappa b activity and use thereof |
| EP2095819A1 (en) | 2008-02-28 | 2009-09-02 | Maastricht University | N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors |
| JP5466759B2 (ja) | 2009-05-28 | 2014-04-09 | ノバルティス アーゲー | ネプリライシン阻害剤としての置換アミノ酪酸誘導体 |
| SG176009A1 (en) | 2009-05-28 | 2011-12-29 | Novartis Ag | Substituted aminopropionic derivatives as neprilysin inhibitors |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| ES2472446T3 (es) * | 2009-11-30 | 2014-07-01 | Novartis Ag | Derivados de imidazol como inhibidores de aldosterona sintasa |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58979A (ja) * | 1981-06-22 | 1983-01-06 | チバ−ガイギ−・アクチエンゲゼルシヤフト | イミダゾ［１，５―ａ］ピリジン誘導体、その製法及びそれを含む医薬組成物 |
| JPS59118785A (ja) * | 1982-12-21 | 1984-07-09 | チバ−ガイギ−・アクチエンゲゼルシヤフト | イミダゾ〔１，５−ａ〕ピリジン誘導体及びその製造方法，並びに該誘導体を含有する医薬 |
| JPS59118784A (ja) * | 1982-12-21 | 1984-07-09 | チバ−ガイギ−・アクチエンゲゼルシヤフト | 置換イミダゾ〔１，５−ａ〕ピリジン及びその製造方法，並びに該化合物を含有する医薬 |
| JPS615076A (ja) * | 1984-06-19 | 1986-01-10 | Toyama Chem Co Ltd | 新規な１，４−ジヒドロピリジン誘導体およびその塩 |
| JPS6112688A (ja) * | 1984-06-20 | 1986-01-21 | チバ・ガイギー・アクチエンゲゼルシヤフト | 置換双環化合物、その製造方法およびその用途ならびにそれを含む医薬製剤 |
| GB2174094A (en) * | 1985-04-25 | 1986-10-29 | Wyeth John & Brother Ltd | Imidazo [1,5-a] pyridine derivatives |
| JPH0971586A (ja) * | 1995-09-07 | 1997-03-18 | Yamanouchi Pharmaceut Co Ltd | 新規な二環性縮合イミダゾール誘導体 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889861A (en) | 1982-12-21 | 1989-12-26 | Ciba-Geigy Corp. | Substituted imidazo[1,5-a]pyridine derivatives and other substituted bicyclic derivatives and their use as aromatase inhibitors |
| US5428160A (en) * | 1982-12-21 | 1995-06-27 | Ciba-Geigy Corporation | Substituted imidazo[5-a]pyridine derviatives and other substituted bicyclic derivatives |
| US5798364A (en) | 1992-03-26 | 1998-08-25 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Imidazopyridines |
| US6150347A (en) | 1992-04-21 | 2000-11-21 | The Curators Of The University Of Missouri | Use of aldosterone antagonists to inhibit myocardial fibrosis |
| US5529992A (en) | 1992-04-21 | 1996-06-25 | Curators Of The University Of Missouri | Method for inhibiting myocardial fibrosis by administering an aldosterone antagonist which suppresses aldoster one receptors |
| DE19701257A1 (de) * | 1997-01-17 | 1998-07-23 | Hannecke Wolf D Kunststoff | Säulenpräsentationssystem in Modulbauweise zur Schaustellung von Waren oder Prospektmaterial und insbesondere von dünnen Gegenständen |
| US6887870B1 (en) | 1999-10-12 | 2005-05-03 | Bristol-Myers Squibb Company | Heterocyclic sodium/proton exchange inhibitors and method |
-
2003
- 2003-11-17 CN CNB2003801035050A patent/CN100447142C/zh not_active Expired - Fee Related
- 2003-11-17 EP EP03767563A patent/EP1565463B1/en not_active Expired - Lifetime
- 2003-11-17 US US10/534,631 patent/US7223866B2/en not_active Expired - Fee Related
- 2003-11-17 CA CA002505752A patent/CA2505752A1/en not_active Abandoned
- 2003-11-17 AU AU2003292039A patent/AU2003292039A1/en not_active Abandoned
- 2003-11-17 ES ES03767563T patent/ES2305520T3/es not_active Expired - Lifetime
- 2003-11-17 WO PCT/EP2003/012851 patent/WO2004046145A1/en not_active Ceased
- 2003-11-17 DE DE60321593T patent/DE60321593D1/de not_active Expired - Lifetime
- 2003-11-17 JP JP2004552632A patent/JP2006508970A/ja active Pending
- 2003-11-17 PT PT03767563T patent/PT1565463E/pt unknown
- 2003-11-17 BR BR0316306-7A patent/BR0316306A/pt not_active IP Right Cessation
- 2003-11-17 AT AT03767563T patent/ATE398124T1/de not_active IP Right Cessation
-
2007
- 2007-04-24 US US11/739,290 patent/US7713991B2/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58979A (ja) * | 1981-06-22 | 1983-01-06 | チバ−ガイギ−・アクチエンゲゼルシヤフト | イミダゾ［１，５―ａ］ピリジン誘導体、その製法及びそれを含む医薬組成物 |
| JPS59118785A (ja) * | 1982-12-21 | 1984-07-09 | チバ−ガイギ−・アクチエンゲゼルシヤフト | イミダゾ〔１，５−ａ〕ピリジン誘導体及びその製造方法，並びに該誘導体を含有する医薬 |
| JPS59118784A (ja) * | 1982-12-21 | 1984-07-09 | チバ−ガイギ−・アクチエンゲゼルシヤフト | 置換イミダゾ〔１，５−ａ〕ピリジン及びその製造方法，並びに該化合物を含有する医薬 |
| JPS615076A (ja) * | 1984-06-19 | 1986-01-10 | Toyama Chem Co Ltd | 新規な１，４−ジヒドロピリジン誘導体およびその塩 |
| JPS6112688A (ja) * | 1984-06-20 | 1986-01-21 | チバ・ガイギー・アクチエンゲゼルシヤフト | 置換双環化合物、その製造方法およびその用途ならびにそれを含む医薬製剤 |
| GB2174094A (en) * | 1985-04-25 | 1986-10-29 | Wyeth John & Brother Ltd | Imidazo [1,5-a] pyridine derivatives |
| JPH0971586A (ja) * | 1995-09-07 | 1997-03-18 | Yamanouchi Pharmaceut Co Ltd | 新規な二環性縮合イミダゾール誘導体 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010520869A (ja) * | 2007-03-09 | 2010-06-17 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのイミダゾ［１，５−ａ］ピリジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100447142C (zh) | 2008-12-31 |
| EP1565463A1 (en) | 2005-08-24 |
| WO2004046145A1 (en) | 2004-06-03 |
| HK1081540A1 (en) | 2006-05-19 |
| DE60321593D1 (de) | 2008-07-24 |
| AU2003292039A1 (en) | 2004-06-15 |
| US20070197582A1 (en) | 2007-08-23 |
| PT1565463E (pt) | 2008-09-10 |
| EP1565463B1 (en) | 2008-06-11 |
| US20060058342A1 (en) | 2006-03-16 |
| ES2305520T3 (es) | 2008-11-01 |
| US7223866B2 (en) | 2007-05-29 |
| CA2505752A1 (en) | 2004-06-03 |
| US7713991B2 (en) | 2010-05-11 |
| ATE398124T1 (de) | 2008-07-15 |
| CN1711262A (zh) | 2005-12-21 |
| BR0316306A (pt) | 2005-09-27 |
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