SK6052002A3 - Nonpeptide substituted benzothiazepines as vasopressin antagonists - Google Patents

Nonpeptide substituted benzothiazepines as vasopressin antagonists Download PDF

Info

Publication number: SK6052002A3
Authority: SK; Slovakia
Prior art keywords: compound; substituted; group; formula; aryl
Prior art date: 1999-11-04

Application number

SK605-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Maud J Urbanski

Robert H K Chen

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.)

1999-11-04

Filing date

2000-11-02

Publication date

2003-09-11

2000-11-02 Application filed by Ortho Mcneil Pharm Inc filed Critical Ortho Mcneil Pharm Inc

2003-09-11 Publication of SK6052002A3 publication Critical patent/SK6052002A3/sk

Links

150000007657 benzothiazepines Chemical class 0.000 title description 4
229940116211 Vasopressin antagonist Drugs 0.000 title description 2
239000003038 vasopressin antagonist Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 156
238000000034 method Methods 0.000 claims abstract description 34
206010019280 Heart failures Diseases 0.000 claims abstract description 24
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
230000002792 vascular Effects 0.000 claims abstract description 16
206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 15
206010020772 Hypertension Diseases 0.000 claims abstract description 10
208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 9
201000006370 kidney failure Diseases 0.000 claims abstract description 9
206010016807 Fluid retention Diseases 0.000 claims abstract description 7
208000019425 cirrhosis of liver Diseases 0.000 claims abstract description 7
206010003225 Arteriospasm coronary Diseases 0.000 claims abstract description 6
208000003890 Coronary Vasospasm Diseases 0.000 claims abstract description 6
201000011634 coronary artery vasospasm Diseases 0.000 claims abstract description 6
208000031225 myocardial ischemia Diseases 0.000 claims abstract description 6
201000006474 Brain Ischemia Diseases 0.000 claims abstract description 4
206010048962 Brain oedema Diseases 0.000 claims abstract description 4
208000006011 Stroke Diseases 0.000 claims abstract description 4
208000007536 Thrombosis Diseases 0.000 claims abstract description 4
208000006752 brain edema Diseases 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 93
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 40
-1 N-morpholino Chemical group 0.000 claims description 35
125000000217 alkyl group Chemical group 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
125000003118 aryl group Chemical group 0.000 claims description 24
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
125000001072 heteroaryl group Chemical group 0.000 claims description 20
201000010099 disease Diseases 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 16
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000003107 substituted aryl group Chemical group 0.000 claims description 13
125000005157 alkyl carboxy group Chemical group 0.000 claims description 12
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 11
239000003937 drug carrier Substances 0.000 claims description 11
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
125000000547 substituted alkyl group Chemical group 0.000 claims description 9
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
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238000006243 chemical reaction Methods 0.000 claims description 7
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125000004093 cyano group Chemical group *C#N 0.000 claims description 6
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ZCBODFKVJVUZQS-UHFFFAOYSA-N 3-[5-[4-[(2-phenylbenzoyl)amino]benzoyl]-2h-1,5-benzothiazepin-2-yl]propanoic acid Chemical compound C1=CC(CCC(=O)O)SC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 ZCBODFKVJVUZQS-UHFFFAOYSA-N 0.000 claims description 2
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239000008174 sterile solution Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
NUMQCACRALPSHD-UHFFFAOYSA-N tert-Butyl ethyl ether Natural products CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- 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
- A61P9/10—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)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Hematology (AREA)
Diabetes (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

SK605-2002A 1999-11-04 2000-11-02 Nonpeptide substituted benzothiazepines as vasopressin antagonists SK6052002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US16354499P	1999-11-04	1999-11-04
PCT/US2000/030114 WO2001032639A1 (en)	1999-11-04	2000-11-02	Nonpeptide substituted benzothiazepines as vasopressin antagonists

Publications (1)

Publication Number	Publication Date
SK6052002A3 true SK6052002A3 (en)	2003-09-11

Family

ID=22590503

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK605-2002A SK6052002A3 (en)	1999-11-04	2000-11-02	Nonpeptide substituted benzothiazepines as vasopressin antagonists

Country Status (17)

Country	Link
US (1)	US6489321B1 (cs)
EP (1)	EP1226132A1 (cs)
JP (1)	JP2003513082A (cs)
KR (1)	KR20020047321A (cs)
CN (1)	CN1414958A (cs)
AR (1)	AR026360A1 (cs)
AU (1)	AU778810B2 (cs)
BR (1)	BR0015299A (cs)
CA (1)	CA2389439A1 (cs)
CZ (1)	CZ20021492A3 (cs)
HU (1)	HUP0204278A2 (cs)
MX (1)	MXPA02004513A (cs)
PL (1)	PL354759A1 (cs)
RU (1)	RU2002111660A (cs)
SK (1)	SK6052002A3 (cs)
WO (1)	WO2001032639A1 (cs)
YU (1)	YU32702A (cs)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE0102764D0 (sv)	2001-08-17	2001-08-17	Astrazeneca Ab	Compounds
AR051780A1 (es) *	2004-11-29	2007-02-07	Japan Tobacco Inc	Compuestos en anillo fusionados que contienen nitrogeno y utilizacion de los mismos
JP3988832B2 (ja) *	2004-11-29	2007-10-10	日本たばこ産業株式会社	窒素含有縮合環化合物及びその用途
KR20110084339A (ko)	2005-07-09	2011-07-21	아스트라제네카 아베	당뇨병 치료에 있어 ｇｌｋ 활성화제로서 사용하기 위한 헤테로아릴 벤즈아미드 유도체
JO3109B1 (ar) *	2012-05-10	2017-09-20	Ferring Bv	منبهات لمستقبلات v1a

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2751287B2 (ja) *	1989-01-09	1998-05-18	吉富製薬株式会社	１，５‐ベンゾチアゼピン‐２‐カルボン酸アミド化合物
KR0167349B1 (ko) *	1989-10-20	1999-02-18	오스카 아끼히꼬	벤조헤테로 고리 화합물
TW199153B (cs)	1990-08-07	1993-02-01	Dtsuka Seiyaku Kk
JPH05320135A (ja)	1992-05-19	1993-12-03	Yamanouchi Pharmaceut Co Ltd	テトラヒドロベンズアゼピン誘導体
JPH0680641A (ja)	1992-09-01	1994-03-22	Otsuka Pharmaceut Co Ltd	光学活性な５−ヒドロキシベンゾアゼピン誘導体の製造法
SK94393A3 (en)	1992-09-11	1994-08-10	Thomae Gmbh Dr K	Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those
CN1052224C (zh)	1993-04-07	2000-05-10	大塚制药株式会社	哌啶衍生物、含有它的外周血管舒张剂及其应用
US6297269B1 (en)	1995-06-06	2001-10-02	Pfizer Inc.	Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors
MX9709875A (es)	1995-06-06	1998-03-31	Pfizer	N-(indol-2-carbonil)-glicinamidas substituidas y derivados como inhibidores de glicogeno fosforilasa, composiciones que las contienen y uso de las mismas.
US6204260B1 (en)	1996-02-23	2001-03-20	Eli Lilly And Company	Non-peptidyl vasopressin V1a antagonists
DE59711622D1 (de)	1996-09-10	2004-06-17	Boehringer Ingelheim Pharma	Abgewandelte aminosäuren, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
US5952322A (en)	1996-12-05	1999-09-14	Pfizer Inc.	Method of reducing tissue damage associated with non-cardiac ischemia using glycogen phosphorylase inhibitors
US6063796A (en)	1997-04-04	2000-05-16	Merck & Co., Inc.	Somatostatin agonists
US6025372A (en)	1997-04-04	2000-02-15	Merck & Co., Inc.	Somatostatin agonists
US6057338A (en)	1997-04-04	2000-05-02	Merck & Co., Inc.	Somatostatin agonists
DE19748763A1 (de)	1997-11-05	1999-05-06	Hans Peter Zenner	Verwendung von Vasopressin-Antagonisten
AUPP150098A0 (en)	1998-01-27	1998-02-19	Fujisawa Pharmaceutical Co., Ltd.	Benzamide derivatives
HUP0202648A3 (en)	1998-06-12	2003-02-28	Sod Conseils Rech Applic	Imidazolyl derivatives, pharmaceutical compositions containing them and their use
JP2002525371A (ja)	1998-09-30	2002-08-13	メルクシャープエンドドームリミテッド	Ｃｇｒｐリガンドとしてのベンゾイミダゾリニルピペリジン
GB9823873D0 (en)	1998-10-30	1998-12-30	Pharmacia & Upjohn Spa	2-ureido-thiazole derivatives,process for their preparation,and their use as antitumour agents
US6297234B1 (en)	1999-02-04	2001-10-02	American Home Products Corporation	Arylthiophene vasopressin agonists

2000
- 2000-11-02 SK SK605-2002A patent/SK6052002A3/sk unknown
- 2000-11-02 CN CN00818031A patent/CN1414958A/zh active Pending
- 2000-11-02 EP EP00980254A patent/EP1226132A1/en not_active Withdrawn
- 2000-11-02 HU HU0204278A patent/HUP0204278A2/hu unknown
- 2000-11-02 BR BR0015299-4A patent/BR0015299A/pt not_active Application Discontinuation
- 2000-11-02 JP JP2001534790A patent/JP2003513082A/ja active Pending
- 2000-11-02 RU RU2002111660/04A patent/RU2002111660A/ru not_active Application Discontinuation
- 2000-11-02 PL PL00354759A patent/PL354759A1/xx not_active Application Discontinuation
- 2000-11-02 WO PCT/US2000/030114 patent/WO2001032639A1/en not_active Ceased
- 2000-11-02 KR KR1020027005650A patent/KR20020047321A/ko not_active Withdrawn
- 2000-11-02 YU YU32702A patent/YU32702A/sh unknown
- 2000-11-02 CA CA002389439A patent/CA2389439A1/en not_active Abandoned
- 2000-11-02 CZ CZ20021492A patent/CZ20021492A3/cs unknown
- 2000-11-02 AU AU17540/01A patent/AU778810B2/en not_active Ceased
- 2000-11-02 MX MXPA02004513A patent/MXPA02004513A/es unknown
- 2000-11-02 US US09/704,314 patent/US6489321B1/en not_active Expired - Fee Related
- 2000-11-03 AR ARP000105813A patent/AR026360A1/es unknown

Also Published As

Publication number	Publication date
AU778810B2 (en)	2004-12-23
KR20020047321A (ko)	2002-06-21
US6489321B1 (en)	2002-12-03
RU2002111660A (ru)	2003-11-27
BR0015299A (pt)	2003-04-15
WO2001032639A1 (en)	2001-05-10
CA2389439A1 (en)	2001-05-10
CN1414958A (zh)	2003-04-30
EP1226132A1 (en)	2002-07-31
YU32702A (sh)	2005-06-10
HUP0204278A2 (hu)	2003-04-28
CZ20021492A3 (cs)	2003-06-18
JP2003513082A (ja)	2003-04-08
AU1754001A (en)	2001-05-14
MXPA02004513A (es)	2004-09-10
AR026360A1 (es)	2003-02-05
PL354759A1 (en)	2004-02-23

Publication	Publication Date	Title
EP2170831B1 (en)	2012-02-15	Benzazepine derivatives useful as vasopressin antagonists
KR100899297B1 (ko)	2009-05-26	플리반세린의 안정한 다형체, 이의 기술적 제조 방법 및 이를 포함하는 약제학적 조성물
CZ267595A3 (en)	1996-04-17	1,5-benzodiazepine derivatives, process of their preparation, their use and pharmaceutical preparations containing thereof
AU5320200A (en)	2001-03-19	Npy antagonists: spiroisoquinolinone derivatives
WO2009066041A2 (fr)	2009-05-28	Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US6495542B1 (en)	2002-12-17	Benzamide derivatives as vasopressin antagonists
CN1449386B (zh)	2012-07-04	作为血管升压素拮抗剂的非肽取代的螺苯并氮杂*
GB2272439A (en)	1994-05-18	Benzo-fused lactams that inhibit the release of growth hormone
AU2001271780A1 (en)	2002-04-11	Nonpeptide substituted spirobenzoazepines as vasopressin antagonists
JP3922024B2 (ja)	2007-05-30	１，５−ベンゾジアゼピン誘導体カルシウム塩及びその製造法並びに該化合物を有効成分とする医薬
US6489321B1 (en)	2002-12-03	Nonpeptide substituted benzothiazepines as vasopressin antagonists
JPWO2001040197A1 (ja)	2003-06-03	１，５−ベンゾジアゼピン誘導体カルシウム塩及びその製造法並びに該化合物を有効成分とする医薬
KR100382998B1 (ko)	2003-08-27	6-메톡시-1h-벤조트리아졸-5-카르복사미드유도체,그제조방법및그것을함유하는의약조성물
US6765004B1 (en)	2004-07-20	Indoloazepines as vasopressin receptor antagonists
CN113784710A (zh)	2021-12-10	用于治疗高血压或心力衰竭的化合物及包含该化合物的组合物
CN113651767B (zh)	2023-06-09	一种苯并异噁唑类杂环化合物及其制备方法和应用
JP3222051B2 (ja)	2001-10-22	６−メトキシ−１ｈ−ベンゾトリアゾール−５−カルボキサミド誘導体
JPH1053528A (ja)	1998-02-24	６−メトキシ−１ｈ−ベンゾトリアゾール−５−カルボキサミド誘導体からなる医薬
HK1141994B (en)	2012-10-05	Benzazepine derivatives useful as vasopressin antagonists
JPH08225571A (ja)	1996-09-03	６−アルコキシ−１ｈ−ベンゾトリアゾール−５−カルボキサミド誘導体及びその中間体並びに該化合物を含有する医薬組成物