ATE405561T1 - Ethylenediaminderivate und ihre verwendung als orexinrezeptorantagonisten - Google Patents
Ethylenediaminderivate und ihre verwendung als orexinrezeptorantagonistenInfo
- Publication number
- ATE405561T1 ATE405561T1 AT02785673T AT02785673T ATE405561T1 AT E405561 T1 ATE405561 T1 AT E405561T1 AT 02785673 T AT02785673 T AT 02785673T AT 02785673 T AT02785673 T AT 02785673T AT E405561 T1 ATE405561 T1 AT E405561T1
- Authority
- AT
- Austria
- Prior art keywords
- receptor antagonists
- orexin receptor
- ethylenediamine derivatives
- derivatives
- ethylenediamine
- Prior art date
Links
- 239000003814 drug Substances 0.000 abstract 1
- 125000003916 ethylene diamine group Chemical class 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/22—Anxiolytics
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- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Addiction (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0130341.1A GB0130341D0 (en) | 2001-12-19 | 2001-12-19 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE405561T1 true ATE405561T1 (de) | 2008-09-15 |
Family
ID=9927922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT02785673T ATE405561T1 (de) | 2001-12-19 | 2002-12-13 | Ethylenediaminderivate und ihre verwendung als orexinrezeptorantagonisten |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7468367B2 (de) |
| EP (1) | EP1456203B1 (de) |
| JP (1) | JP2005519038A (de) |
| AT (1) | ATE405561T1 (de) |
| AU (1) | AU2002350961A1 (de) |
| DE (1) | DE60228487D1 (de) |
| ES (1) | ES2312641T3 (de) |
| GB (1) | GB0130341D0 (de) |
| WO (1) | WO2003051872A1 (de) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0315115A (pt) | 2002-10-11 | 2005-08-16 | Actelion Pharmaceuticals Ltd | Compostos, composições farmacêuticas, método para tratar ou prevenir doenças ou distúrbios em que se requer um antagonista de receptores de orexina humana, processo para a fabricação de composições farmacêuticas, e, uso de um ou mais compostos em combinação com outros compostos farmacologicamente ativos |
| ES2297413T3 (es) | 2003-04-28 | 2008-05-01 | Actelion Pharmaceuticals Ltd. | Derivados de quinoxalinona-3-ona utilizados como antagonistas del receptor de orexina. |
| HUP0400405A3 (en) * | 2004-02-10 | 2009-03-30 | Sanofi Synthelabo | Pyrimidine derivatives, process for producing them, their use, pharmaceutical compositions containing them and their intermediates |
| JP4094050B2 (ja) | 2004-03-01 | 2008-06-04 | アクテリオン ファーマシューティカルズ リミテッド | 置換1,2,3,4−テトラヒドロイソキノリン誘導体 |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
| JP2010527924A (ja) | 2007-05-18 | 2010-08-19 | メルク・シャープ・エンド・ドーム・コーポレイション | オキソ架橋ジアゼパンオレキシン受容体アンタゴニスト |
| US8030495B2 (en) | 2007-05-23 | 2011-10-04 | Coleman Paul J | Cyclopropyl pyrrolidine orexin receptor antagonists |
| WO2008147518A1 (en) | 2007-05-23 | 2008-12-04 | Merck & Co., Inc. | Pyridyl piperidine orexin receptor antagonists |
| WO2009011775A1 (en) * | 2007-07-13 | 2009-01-22 | Merck & Co., Inc. | Amidoethyl alkylamino orexin receptor antagonists |
| CA2695621A1 (en) * | 2007-08-09 | 2009-02-12 | Merck Sharp & Dohme Corp. | Pyridine carboxamide orexin receptor antagonists |
| BRPI0815079A2 (pt) * | 2007-08-15 | 2015-02-03 | Actelion Pharmaceuticals Ltd | Composto dericado de 1,2-diamido-etileno, composição farmacêutica que contém e uso desse composto |
| CA2705411A1 (en) * | 2007-12-21 | 2009-07-02 | F. Hoffmann-La Roche Ag | Heteroaryl derivatives as orexin receptor antagonists |
| AR072899A1 (es) | 2008-08-07 | 2010-09-29 | Merck Sharp & Dohme | Derivados de terpiridina-carboxamida antagonistas de receptores de orexina, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento del insomnio y la obesidad. |
| EP2350010B1 (de) * | 2008-10-30 | 2014-03-26 | Merck Sharp & Dohme Corp. | Isonikotinamide als orexinrezeptorantagonisten |
| EP2438041A4 (de) * | 2009-06-01 | 2012-11-21 | Merck Sharp & Dohme | Pyrazin-carboxamid-orexin-rezeptorantagonisten |
| ES2585806T3 (es) | 2009-10-23 | 2016-10-10 | Janssen Pharmaceutica N.V. | Octahidropirrolo [3,4-c] pirroles disustituidos como moduladores de receptores de orexina |
| WO2011050202A1 (en) | 2009-10-23 | 2011-04-28 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| EP2491034B1 (de) | 2009-10-23 | 2013-12-18 | Janssen Pharmaceutica, N.V. | Kondensierte heterocyclische verbindungen als orexinrezeptormodulatoren |
| WO2012145581A1 (en) | 2011-04-20 | 2012-10-26 | Janssen Pharmaceutica Nv | Disubstituted octahy-dropyrrolo [3,4-c] pyrroles as orexin receptor modulators |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| WO2013119639A1 (en) | 2012-02-07 | 2013-08-15 | Eolas Therapeutics, Inc. | Substituted prolines / piperidines as orexin receptor antagonists |
| TW201613864A (en) * | 2014-02-20 | 2016-04-16 | Takeda Pharmaceutical | Novel compounds |
| TW201613902A (en) | 2014-08-13 | 2016-04-16 | Eolas Therapeutics Inc | Difluoropyrrolidines as orexin receptor modulators |
| GB201415569D0 (en) * | 2014-09-03 | 2014-10-15 | C4X Discovery Ltd | Therapeutic Compounds |
| GB201601703D0 (en) * | 2016-01-29 | 2016-03-16 | C4X Discovery Ltd | Therapeutic compounds |
| LT3414241T (lt) | 2016-02-12 | 2022-08-25 | Astrazeneca Ab | Halogenu pakeisti piperidinai kaip oreksino receptoriaus moduliatoriai |
| HRP20220642T1 (hr) | 2016-03-10 | 2022-06-24 | Janssen Pharmaceutica Nv | Postupci za liječenje depresije uporabom antagonista receptora oreksina 2 |
| US10738031B2 (en) | 2016-04-15 | 2020-08-11 | Boehringer Ingelheim International Gmbh | N-[(heteroaryloxy)propanyl]heteroaryl carboxamides as antagonists of orexin subtype 1 receptor activity |
| EP3442963B1 (de) | 2016-04-15 | 2020-05-06 | Boehringer Ingelheim International GmbH | N-[(pyrazinyloxy)propanyl]benzamide |
| EP3442967B1 (de) | 2016-04-15 | 2020-05-13 | Boehringer Ingelheim International GmbH | Neuartige n-[(pyrimidinyloxy)propanyl]benzamide |
| JP6918827B2 (ja) * | 2016-04-15 | 2021-08-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なn−[(ピリジルオキシ)プロパニル]ベンズアミド |
| US10710984B2 (en) * | 2016-04-15 | 2020-07-14 | Boehringer Ingelheim International Gmbh | N-[(Pyrimidinylamino)propanyl]-and N-[(Pyridinylamino)-propanyl]arylcarboxamides |
| JP6591698B2 (ja) * | 2016-04-15 | 2019-10-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なn−[(ピリミジニルアミノ)プロパニル]−およびn−[(ピラジニルアミノ)プロパニル]アリールカルボキサミド |
| WO2017194548A1 (en) | 2016-05-10 | 2017-11-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| GB201702174D0 (en) | 2017-02-09 | 2017-03-29 | Benevolentai Bio Ltd | Orexin receptor antagonists |
| GB201707504D0 (en) | 2017-05-10 | 2017-06-21 | Benevolentai Bio Ltd | Orexin receptor antagonists |
| GB201707499D0 (en) | 2017-05-10 | 2017-06-21 | Benevolentai Bio Ltd | Orexin receptor antagonists |
| EP3661928B1 (de) | 2017-07-31 | 2021-06-16 | Boehringer Ingelheim International GmbH | N-[(pyrimidinylamino)propanyl]-, n-[(pyridylamino)propanyl]- und n-[(pyrazinylamino)propanyl]arylcarboxamide |
| JP6874217B2 (ja) * | 2017-09-28 | 2021-05-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なn−(2,2−ジフルオロエチル)−n−[(ピリミジニルアミノ)プロパニル]アリールカルボキサミド |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05507702A (ja) | 1990-05-30 | 1993-11-04 | アメリカン・ホーム・プロダクツ・コーポレイション | 置換アリールスルホンアミド類およびベンズアミド類 |
| US5149700A (en) * | 1990-05-30 | 1992-09-22 | American Home Products Corporation | Substituted arylsulfonamides and benzamides |
| DK0556310T3 (da) * | 1990-11-06 | 1995-08-21 | Pfizer | Quinazolinderivater til forhøjelse af antitumoraktivitet |
| EP0876345B1 (de) * | 1995-10-16 | 2004-08-18 | Fujisawa Pharmaceutical Co., Ltd. | Heterocyclische verbindungen als h+-atpasen |
| KR19990076877A (ko) * | 1995-12-29 | 1999-10-25 | 스티븐 베네티아너 | 비트로넥틴 수용체 길항제 |
| WO2000047576A1 (en) * | 1999-02-12 | 2000-08-17 | Smithkline Beecham Plc | Cinnamide derivatives as orexin-1 receptors antagonists |
| US6699879B1 (en) * | 1999-02-12 | 2004-03-02 | Smithkline Beecham P.L.C. | Phenyl urea and phenyl thiourea derivatives as orexin receptor antagonists |
| US6514964B1 (en) * | 1999-09-27 | 2003-02-04 | Amgen Inc. | Fused cycloheptane and fused azacycloheptane compounds and their methods of use |
| MXPA03011002A (es) | 2001-06-06 | 2004-10-28 | Agouron Pharma | Agentes gnrh no peptidicos, composiciones farmaceuticas y procedimientos para su uso y procesos para prepararlos a ellos y a sus intermedios. |
-
2001
- 2001-12-19 GB GBGB0130341.1A patent/GB0130341D0/en not_active Ceased
-
2002
- 2002-12-13 AU AU2002350961A patent/AU2002350961A1/en not_active Abandoned
- 2002-12-13 DE DE60228487T patent/DE60228487D1/de not_active Expired - Lifetime
- 2002-12-13 JP JP2003552756A patent/JP2005519038A/ja active Pending
- 2002-12-13 EP EP02785673A patent/EP1456203B1/de not_active Expired - Lifetime
- 2002-12-13 WO PCT/GB2002/005665 patent/WO2003051872A1/en not_active Ceased
- 2002-12-13 AT AT02785673T patent/ATE405561T1/de not_active IP Right Cessation
- 2002-12-13 ES ES02785673T patent/ES2312641T3/es not_active Expired - Lifetime
- 2002-12-13 US US10/498,884 patent/US7468367B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2312641T3 (es) | 2009-03-01 |
| JP2005519038A (ja) | 2005-06-30 |
| AU2002350961A1 (en) | 2003-06-30 |
| EP1456203B1 (de) | 2008-08-20 |
| DE60228487D1 (de) | 2008-10-02 |
| EP1456203A1 (de) | 2004-09-15 |
| WO2003051872A1 (en) | 2003-06-26 |
| US7468367B2 (en) | 2008-12-23 |
| US20050159421A1 (en) | 2005-07-21 |
| GB0130341D0 (en) | 2002-02-06 |
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