NO327896B1 - Tricykliske benzodiazepiner, farmasoytisk sammensetning, anvendelse av forbindelsene samt mellomprodukter som er nyttige ved syntese av forbindelsene - Google Patents

Tricykliske benzodiazepiner, farmasoytisk sammensetning, anvendelse av forbindelsene samt mellomprodukter som er nyttige ved syntese av forbindelsene Download PDF

Info

Publication number: NO327896B1
Authority: NO; Norway
Prior art keywords: phenyl; benzodiazepine; benzamide; tetrahydro; ylcarbonyl
Prior art date: 1999-01-19

Application number

NO20013515A

Other languages

English (en)

Norwegian (no)

Other versions

NO20013515L (no

NO20013515D0 (no

Inventor

William J Hoekstra

Alexey B Dyatkin

Jay M Matthews

Bruce E Maryanoff

Original Assignee

Ortho Mcneil Pharm Inc

Priority date (The priority date 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 date listed.)

1999-01-19

Filing date

2001-07-16

Publication date

2009-10-12

2001-07-16 Application filed by Ortho Mcneil Pharm Inc filed Critical Ortho Mcneil Pharm Inc

2001-07-16 Publication of NO20013515D0 publication Critical patent/NO20013515D0/no

2001-09-17 Publication of NO20013515L publication Critical patent/NO20013515L/no

2009-10-12 Publication of NO327896B1 publication Critical patent/NO327896B1/no

Links

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Classifications

- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)

NO20013515A 1999-01-19 2001-07-16 Tricykliske benzodiazepiner, farmasoytisk sammensetning, anvendelse av forbindelsene samt mellomprodukter som er nyttige ved syntese av forbindelsene NO327896B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US11635899P	1999-01-19	1999-01-19
US46865099A	1999-12-21	1999-12-21
PCT/US1999/030423 WO2000043398A2 (en)	1999-01-19	1999-12-21	Tricyclic benzodiazepines as vasopressin receptor antagonists

Publications (3)

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NO20013515D0 NO20013515D0 (no)	2001-07-16
NO20013515L NO20013515L (no)	2001-09-17
NO327896B1 true NO327896B1 (no)	2009-10-12

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NO20013515A NO327896B1 (no)	1999-01-19	2001-07-16	Tricykliske benzodiazepiner, farmasoytisk sammensetning, anvendelse av forbindelsene samt mellomprodukter som er nyttige ved syntese av forbindelsene

Country Status (27)

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US (2)	US6713475B2 (sr)
EP (1)	EP1147115B3 (sr)
KR (1)	KR100771184B1 (sr)
CN (1)	CN1174986C (sr)
AR (1)	AR035837A1 (sr)
AT (1)	ATE249465T1 (sr)
AU (1)	AU772397B2 (sr)
BR (1)	BRPI9917086B8 (sr)
CA (1)	CA2360767C (sr)
CZ (1)	CZ302647B6 (sr)
DE (2)	DE69911259D1 (sr)
DK (1)	DK1147115T5 (sr)
ES (1)	ES2207333T7 (sr)
HK (1)	HK1038361B (sr)
HU (1)	HU229074B1 (sr)
IL (2)	IL144270A0 (sr)
ME (1)	ME00129B (sr)
MY (1)	MY128065A (sr)
NO (1)	NO327896B1 (sr)
NZ (1)	NZ512960A (sr)
PL (1)	PL205704B1 (sr)
PT (1)	PT1147115E (sr)
RS (1)	RS50820B (sr)
TR (1)	TR200102069T2 (sr)
TW (1)	TWI289564B (sr)
UA (1)	UA70984C2 (sr)
WO (1)	WO2000043398A2 (sr)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU772397B2 (en) *	1999-01-19	2004-04-29	Ortho-Mcneil Pharmaceutical, Inc.	Tricyclic benzodiazepines as vasopressin receptor antagonists
ES2288899T3 (es) *	2000-10-04	2008-02-01	Astellas Pharma Inc.	Uso de un antagonista de vasopresina tal como conivaptan en la fabricacion de un medicamento para el tratamiento de la hipertension pulmonar.
US7053083B2 (en)	2001-04-12	2006-05-30	Wyeth	Cyclohexylphenyl vasopressin agonists
JP2004530668A (ja)	2001-04-12	2004-10-07	ワイス	バソプレッシンアゴニストとしてのｎ−ビフェニルカルボニル−およびｎ−フェニルピリジルカルボニル置換二および三環アゼピンおよびジアゼピン
HUP0401722A3 (en)	2001-10-29	2008-07-28	Ortho Mcneil Pharm Inc	Benzo[e][1,4]diazepine derivatives condensed with bridged bicycle, their preparation and their use as vasopressin receptor antagonists
EP1364968A1 (en) *	2002-05-23	2003-11-26	Bayer Aktiengesellschaft	Diagnostics and therapeutics for diseases associated with arginine vasopressin receptor 1 (AVPR1)
GB0303852D0 (en) *	2003-02-19	2003-03-26	Pfizer Ltd	Triazole compounds useful in therapy
AP2005003376A0 (en) *	2003-02-19	2005-09-30	Pfizer	Triazole compounds useful in therapy.
US7119088B2 (en)	2003-02-19	2006-10-10	Pfizer Inc.	Triazole compounds useful in therapy
JP2008518915A (ja)	2004-10-28	2008-06-05	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	バソプレシンｖ２受容体アンタゴニストとしての新規な［１，４］ベンゾジアゼピン
DE102005003632A1 (de)	2005-01-20	2006-08-17	Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.	Katheter für die transvaskuläre Implantation von Herzklappenprothesen
US20070213813A1 (en)	2005-12-22	2007-09-13	Symetis Sa	Stent-valves for valve replacement and associated methods and systems for surgery
US20090318412A1 (en) *	2006-07-11	2009-12-24	Takahiro Matsumoto	Tricyclic heterocyclic compound and use thereof
US7896915B2 (en)	2007-04-13	2011-03-01	Jenavalve Technology, Inc.	Medical device for treating a heart valve insufficiency
WO2011104269A1 (en)	2008-02-26	2011-09-01	Jenavalve Technology Inc.	Stent for the positioning and anchoring of a valvular prosthesis in an implantation site in the heart of a patient
US9044318B2 (en)	2008-02-26	2015-06-02	Jenavalve Technology Gmbh	Stent for the positioning and anchoring of a valvular prosthesis
SI2356123T1 (sl) *	2008-11-13	2013-01-31	F. Hoffmann-La Roche Ag	Piro-5,6-dihidro-4h-2,3,5,10b-tetraaza-benzo(e)azuleni
KR101385433B1 (ko) *	2008-11-18	2014-04-14	에프. 호프만-라 로슈 아게	다이하이드로테트라아자벤조아줄렌의 알킬사이클로헥실에터
HRP20131067T1 (hr) *	2008-11-28	2013-12-06	F. Hoffmann - La Roche Ag	Arilcikloheksileteri od dihidrotetraazabenzoazulena za primjenu kao antagonista receptora vazopresina v1a
DE102009033392A1 (de) *	2009-07-16	2011-01-20	Merck Patent Gmbh	Heterocyclische Verbindungen als Autotaxin-Inhibitoren II
JP2013505914A (ja) *	2009-09-24	2013-02-21	シャイア−モベティスエヌ．ブイ．	バソプレシンｖ２受容体アンタゴニストとしての［１，４］−ベンゾジアゼピン
US8420633B2 (en)	2010-03-31	2013-04-16	Hoffmann-La Roche Inc.	Aryl-cyclohexyl-tetraazabenzo[e]azulenes
US8461151B2 (en)	2010-04-13	2013-06-11	Hoffmann-La Roche Inc.	Aryl-/heteroaryl-cyclohexenyl-tetraazabenzo[e]azulenes
US8492376B2 (en)	2010-04-21	2013-07-23	Hoffmann-La Roche Inc.	Heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes
US8481528B2 (en)	2010-04-26	2013-07-09	Hoffmann-La Roche Inc.	Heterobiaryl-cyclohexyl-tetraazabenzo[e]azulenes
US8513238B2 (en)	2010-05-10	2013-08-20	Hoffmann-La Roche Inc.	Heteroaryl-cyclohexyl-tetraazabenzo[E]azulenes
US10856978B2 (en)	2010-05-20	2020-12-08	Jenavalve Technology, Inc.	Catheter system
CN103002833B (zh)	2010-05-25	2016-05-11	耶拿阀门科技公司	人工心脏瓣及包括人工心脏瓣和支架的经导管输送的内假体
US8828989B2 (en)	2011-09-26	2014-09-09	Hoffmann-La Roche Inc.	Oxy-cyclohexyl-4H,6H-5-oxa-2,3,10b-triaza-benzo[E]azulenes as V1A antagonists
WO2015028209A1 (en)	2013-08-30	2015-03-05	Jenavalve Technology Gmbh	Radially collapsible frame for a prosthetic valve and method for manufacturing such a frame
EP3226690B1 (en)	2014-12-05	2020-05-20	Merck Sharp & Dohme Corp.	Novel tricyclic compounds as inhibitors of mutant idh enzymes
WO2016089830A1 (en) *	2014-12-05	2016-06-09	Merck Sharp & Dohme Corp.	Novel tricyclic compounds as inhibitors of mutant idh enzymes
US10442819B2 (en)	2014-12-05	2019-10-15	Merck Sharp & Dohme Corp.	Tricyclic compounds as inhibitors of mutant IDH enzymes
WO2016150806A1 (en)	2015-03-20	2016-09-29	Jenavalve Technology, Inc.	Heart valve prosthesis delivery system and method for delivery of heart valve prosthesis with introducer sheath
CN107530168B (zh)	2015-05-01	2020-06-09	耶拿阀门科技股份有限公司	在心脏瓣膜替换中具有降低的起搏器比例的装置和方法
CN109475419B (zh)	2016-05-13	2021-11-09	耶拿阀门科技股份有限公司	用于通过引导鞘和装载系统来递送心脏瓣膜假体的心脏瓣膜假体递送系统和方法
CN110392557A (zh)	2017-01-27	2019-10-29	耶拿阀门科技股份有限公司	心脏瓣膜模拟
EP3875078A1 (en) *	2020-03-06	2021-09-08	Dompe' Farmaceutici S.P.A.	Compounds for the treatment of covid-19
CN120152682A (zh)	2022-11-09	2025-06-13	耶拿阀门科技公司	用于顺序地部署可扩张植入物的导管系统

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3732212A (en)	1970-04-20	1973-05-08	Sterling Drug Inc	1,2,3,10,11,11a-hexahydro-5h-pyrrolo(2,1-c)(1,4)benzodiazepine-5,11-diones
US3860600A (en)	1972-07-10	1975-01-14	Sterling Drug Inc	Octahydropyrrido{8 2,1-c{9 {8 1,4{9 benzodiazepines
US3763183A (en) *	1972-07-10	1973-10-02	Sterling Drug Inc	1,2,3,10,11,11a-hexahydro-5h-pyrrolo (2,1-c)(1,4)benzodiazepines
US5516774A (en) *	1993-07-29	1996-05-14	American Cyanamid Company	Tricyclic diazepine vasopressin antagonists and oxytocin antagonists
US5521173A (en) *	1995-01-17	1996-05-28	American Home Products Corporation	Tricyclic benzazepine vasopressin antagonists
CA2285343A1 (en) *	1997-03-31	1998-10-08	Wakamoto Pharmaceutical Co., Ltd.	Biphenyl derivatives and medicinal compositions
DE69826487T2 (de) *	1997-07-30	2005-12-01	Wyeth	Trizyclische vasopressin-agonisten
AU772397B2 (en) *	1999-01-19	2004-04-29	Ortho-Mcneil Pharmaceutical, Inc.	Tricyclic benzodiazepines as vasopressin receptor antagonists

1999
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Also Published As

Publication number	Publication date
AU772397C (en)	2000-08-07
DE69911259D1 (de)	2003-10-16
BR9917086B1 (pt)	2013-12-03
CZ302647B6 (cs)	2011-08-17
UA70984C2 (uk)	2004-11-15
US20040242866A1 (en)	2004-12-02
HUP0105034A3 (en)	2004-11-29
ES2207333T3 (es)	2004-05-16
AU772397B2 (en)	2004-04-29
KR20010101577A (ko)	2001-11-14
PL205704B1 (pl)	2010-05-31
TWI289564B (en)	2007-11-11
BRPI9917086B8 (pt)	2016-05-24
US20020103373A1 (en)	2002-08-01
EP1147115A2 (en)	2001-10-24
DE69911259T4 (de)	2009-07-09
HK1038361B (en)	2004-05-07
NO20013515L (no)	2001-09-17
TR200102069T2 (tr)	2001-11-21
US7317005B2 (en)	2008-01-08
ES2207333T7 (es)	2009-06-18
AR035837A1 (es)	2004-07-21
PT1147115E (pt)	2004-02-27
US6713475B2 (en)	2004-03-30
AU2201400A (en)	2000-08-07
CZ20012598A3 (cs)	2002-08-14
HU229074B1 (en)	2013-07-29
KR100771184B1 (ko)	2007-10-29
RS50820B (sr)	2010-08-31
PL349778A1 (en)	2002-09-09
DK1147115T3 (da)	2004-01-12
IL144270A0 (en)	2002-05-23
NZ512960A (en)	2004-01-30
WO2000043398A3 (en)	2001-01-11
NO20013515D0 (no)	2001-07-16
HUP0105034A2 (hu)	2002-04-29
ATE249465T1 (de)	2003-09-15
WO2000043398A2 (en)	2000-07-27
HK1038361A1 (en)	2002-03-15
IL144270A (en)	2010-04-29
ME00129B (me)	2010-10-10
CA2360767A1 (en)	2000-07-27
CA2360767C (en)	2009-11-03
CN1174986C (zh)	2004-11-10
YU51901A (sh)	2004-03-12
MEP17808A (en)	2010-06-10
DK1147115T5 (da)	2008-12-08
MY128065A (en)	2007-01-31
CN1339038A (zh)	2002-03-06
BR9917086A (pt)	2001-10-30
EP1147115B3 (en)	2008-12-24
EP1147115B1 (en)	2003-09-10
DE69911259T2 (de)	2004-12-02

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2019-07-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO327896B1 (no)	2009-10-12	Tricykliske benzodiazepiner, farmasoytisk sammensetning, anvendelse av forbindelsene samt mellomprodukter som er nyttige ved syntese av forbindelsene
CA1321996C (en)	1993-09-07	Condensed diazepinones, processes for preparing them and pharmaceutical compositions containing these compounds
EP1370560B1 (en)	2004-11-10	Aminomethyl-pyrroloquinazoline compounds as thrombin receptor antagonists
NZ540768A (en)	2008-05-30	Benzamide derivatives as oxytocin agonists and vasopressin antagonists
RU2250899C2 (ru)	2005-04-27	Трициклические бензодиазепины, фармацевтическая композиция на их основе и способы лечения гипертензии
HU201759B (en)	1990-12-28	Process for producing new condensed diazepinones and pharmaceutical compositions comprising same
US7763605B2 (en)	2010-07-27	[1,4]benzodiazepines as vasopressin V2 receptor antagonists
MXPA01007304A (en)	2002-06-05	Tricyclic benzodiazepines as vasopressin receptor antagonists
JPH0920779A (ja)	1997-01-21	縮合ヘテロ５員環アゼピン化合物類及びその医薬用途
US6936604B2 (en)	2005-08-30	Bridged bicyclic amino acid-derived [1,4]benzodiazepine vasopressin receptor antagonists
NZ227758A (en)	1991-09-25	Tricyclic diazepinone derivatives, preparatory processes and pharmaceutical compositions