NO311133B1 - 1,5-benzodiazepinderivater med CCK-antagonistisk eller agonistisk aktivitet, anvendelse derav, farmasöytisk preparat samtfremgangsmåte for fremstilling derav - Google Patents

1,5-benzodiazepinderivater med CCK-antagonistisk eller agonistisk aktivitet, anvendelse derav, farmasöytisk preparat samtfremgangsmåte for fremstilling derav Download PDF

Info

Publication number: NO311133B1
Authority: NO; Norway
Prior art keywords: group; phenyl; formula; compound; methyl
Prior art date: 1993-04-15

Application number

NO19954090A

Other languages

English (en)

Norwegian (no)

Other versions

NO954090D0 (no

NO954090L (no

Inventor

Elisabeth Ellen Sugg

Christopher Joseph Aquino

Jerzy Ryszard Szewczyk

Harry Finch

Robin Arthur Ellis Carr

Original Assignee

Glaxo Wellcome 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.)

1993-04-15

Filing date

1995-10-13

Publication date

2001-10-15

1995-10-13 Application filed by Glaxo Wellcome Inc filed Critical Glaxo Wellcome Inc

1995-10-13 Publication of NO954090D0 publication Critical patent/NO954090D0/no

1995-12-13 Publication of NO954090L publication Critical patent/NO954090L/no

2001-10-15 Publication of NO311133B1 publication Critical patent/NO311133B1/no

Links

238000000034 method Methods 0.000 title claims description 23
238000002360 preparation method Methods 0.000 title claims description 21
239000000825 pharmaceutical preparation Substances 0.000 title claims description 5
230000008569 process Effects 0.000 title claims description 3
ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical class N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 title 1
230000001270 agonistic effect Effects 0.000 title 1
230000003042 antagnostic effect Effects 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 145
-1 hydroxy, carboxy Chemical group 0.000 claims description 41
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
150000001412 amines Chemical class 0.000 claims description 28
239000000203 mixture Substances 0.000 claims description 28
239000000460 chlorine Substances 0.000 claims description 22
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
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239000001257 hydrogen Substances 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 15
230000000694 effects Effects 0.000 claims description 14
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SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
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AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims description 9
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical group C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
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JBMKRAJRQFJXSG-UHFFFAOYSA-N 3-[[5-(1-amino-3-methyl-1-oxo-2-phenylbutan-2-yl)-2,4-dioxo-1-phenyl-1,5-benzodiazepin-3-yl]carbamoylamino]benzoic acid Chemical group C=1C=CC=CC=1C(C(C)C)(C(N)=O)N(C(C(NC(=O)NC=1C=C(C=CC=1)C(O)=O)C1=O)=O)C2=CC=CC=C2N1C1=CC=CC=C1 JBMKRAJRQFJXSG-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
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229910052736 halogen Inorganic materials 0.000 claims description 3
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125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
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SXEIOMJBLIDGON-UHFFFAOYSA-N [dimethylamino(hydroxy)methyl] hypofluorite Chemical compound CN(C)C(O)OF SXEIOMJBLIDGON-UHFFFAOYSA-N 0.000 claims description 2
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RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
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125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
102100021022 Gastrin Human genes 0.000 claims 1
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239000002023 wood Substances 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Crystallography & Structural Chemistry (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Endocrinology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

NO19954090A 1993-04-15 1995-10-13 1,5-benzodiazepinderivater med CCK-antagonistisk eller agonistisk aktivitet, anvendelse derav, farmasöytisk preparat samtfremgangsmåte for fremstilling derav NO311133B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939307833A GB9307833D0 (en)	1993-04-15	1993-04-15	Modulators of cholecystokinin and gastrin
PCT/EP1994/001131 WO1994024149A1 (en)	1993-04-15	1994-04-14	1,5-benzodiazepine derivatives having cck antagonistic or agonistic activity

Publications (3)

Publication Number	Publication Date
NO954090D0 NO954090D0 (no)	1995-10-13
NO954090L NO954090L (no)	1995-12-13
NO311133B1 true NO311133B1 (no)	2001-10-15

Family

ID=10733915

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19954090A NO311133B1 (no)	1993-04-15	1995-10-13	1,5-benzodiazepinderivater med CCK-antagonistisk eller agonistisk aktivitet, anvendelse derav, farmasöytisk preparat samtfremgangsmåte for fremstilling derav

Country Status (34)

Country	Link
US (2)	US5646140A (es)
EP (1)	EP0694039B1 (es)
JP (1)	JP3406317B2 (es)
KR (1)	KR100364948B1 (es)
CN (1)	CN1058487C (es)
AP (2)	AP512A (es)
AT (1)	ATE198894T1 (es)
AU (1)	AU681139B2 (es)
CA (1)	CA2158973C (es)
CZ (1)	CZ286695B6 (es)
DE (1)	DE69426624T2 (es)
DK (1)	DK0694039T3 (es)
EC (1)	ECSP941066A (es)
ES (1)	ES2154674T3 (es)
FI (1)	FI954853A0 (es)
GB (1)	GB9307833D0 (es)
GR (1)	GR3035641T3 (es)
HK (1)	HK1003943A1 (es)
HU (1)	HU223467B1 (es)
IL (2)	IL109316A (es)
IS (2)	IS4147A (es)
MY (2)	MY131569A (es)
NO (1)	NO311133B1 (es)
NZ (1)	NZ265272A (es)
OA (1)	OA10355A (es)
PE (2)	PE50594A1 (es)
PH (1)	PH30897A (es)
PL (1)	PL178790B1 (es)
PT (1)	PT694039E (es)
RU (1)	RU2135486C1 (es)
SK (1)	SK281211B6 (es)
TW (1)	TW487703B (es)
WO (1)	WO1994024149A1 (es)
ZA (2)	ZA942570B (es)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU684871B2 (en) *	1993-12-28	1998-01-08	Shionogi & Co., Ltd.	Novel benzodiazepine derivative
US5739129A (en) *	1994-04-14	1998-04-14	Glaxo Wellcome Inc.	CCK or gastrin modulating 5-heterocyclic-1, 5 benzodiazepines
NZ283929A (en) *	1994-04-14	1998-02-26	Glaxo Wellcome Inc	5-heterocyclic-1,5-benzodiazepine peptide analogs used to modulate effects of cck or gastrin
WO1995028399A1 (en) *	1994-04-15	1995-10-26	Glaxo Wellcome Inc.	A method of inducing cholecystokinin agonist activity using 1,4-benzodiazepine compounds
PE27497A1 (es) *	1994-04-15	1997-08-07	Glaxo Inc	Derivados de 1,5 benzodiazepina
US5780464A (en) *	1994-10-14	1998-07-14	Glaxo Wellcome Inc.	Enteric coated compositions of 1,5-benzodiazepine derivatives having CCK antagonistic or agonistic activity
US5910495A (en) *	1994-10-14	1999-06-08	Glaxo Wellcome Inc.	Use of 1,5-benzo b!1,4-diazepines to control gastric emptying
GB9420748D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	1,5 benzodiazepine derivatives
GB9420763D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	Acetamide derivatives
GB9420747D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	1,5 benzodiazepine derivatives
WO1997021731A1 (en)	1995-12-11	1997-06-19	New England Medical Center Hospitals, Inc.	Assay for and uses of peptide hormone receptor ligands
US5750353A (en) *	1995-12-11	1998-05-12	New England Medical Center Hospitals, Inc.	Assay for non-peptide agonists to peptide hormone receptors
JP3999819B2 (ja) *	1996-12-10	2007-10-31	ゼリア新薬工業株式会社	１，５―ベンゾジアセピン誘導体
SK141899A3 (en)	1997-04-15	2000-09-12	Csir Corporate Building	Pharmaceutical compositions having appetite suppressant activity
AR022044A1 (es) *	1999-05-06	2002-09-04	Glaxo Group Ltd	Derivados de 1,5-benzodiazepina
GB2396815B (en)	1999-10-27	2004-09-08	Phytopharm Plc	A composition comprising a pregnenone derivative and an NSAID
GB2363985B (en)	2000-06-30	2004-09-29	Phytopharm Plc	Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use
US6768024B1 (en)	2000-08-04	2004-07-27	Lion Bioscience Ag	Triamine derivative melanocortin receptor ligands and methods of using same
US20020180095A1 (en) *	2001-05-29	2002-12-05	Berard Steven O.	Thermally conductive carbon fiber extrusion compounder and method of using same
US7074805B2 (en) *	2002-02-20	2006-07-11	Abbott Laboratories	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
ES2319886T3 (es) *	2002-02-20	2009-05-14	Abbott Laboratories	Compuestos azabiciclicos condensados que inhiben el sutipo 1 del receptor valinoide (vr1).
US6933311B2 (en) *	2003-02-11	2005-08-23	Abbott Laboratories	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US7015233B2 (en) *	2003-06-12	2006-03-21	Abbott Laboratories	Fused compounds that inhibit vanilloid subtype 1 (VR1) receptor
EA010888B1 (ru) *	2004-05-25	2008-12-30	Пфайзер Продактс, Инк.	Тетраазабензо[е]азуленовые производные и их аналоги
CN1333077C (zh) *	2005-04-15	2007-08-22	华南农业大学	缩胆囊素活性片段的串联表达及其应用
TW200824687A (en) *	2006-08-25	2008-06-16	Abbott Lab	Compounds that inhibit TRPV1 and uses thereof
CN101563318A (zh) *	2006-12-20	2009-10-21	艾博特公司	作为trpv1香草素受体拮抗剂用于治疗疼痛的n-(5,6,7,8-四氢萘-1-基)脲衍生物以及相关化合物
CA2719018A1 (en) *	2008-03-20	2009-09-24	Abbott Laboratories	Methods for making central nervous system agents that are trpv1 antagonists
CN103102285B (zh) *	2013-01-30	2015-07-29	淮阴师范学院	对氨基苯乙腈的制备方法
WO2015074064A2 (en)	2013-11-18	2015-05-21	Bair Kenneth W	Tetrahydroquinoline compositions as bet bromodomain inhibitors
US9422281B2 (en)	2013-11-18	2016-08-23	Forma Therapeutics, Inc.	Benzopiperazine compositions as BET bromodomain inhibitors
RS63653B1 (sr)	2015-07-22	2022-11-30	Enanta Pharm Inc	Benzodiazepinski derivati kao inhibitori rsv
SG10201913587WA (en)	2016-02-05	2020-02-27	Denali Therapeutics Inc	Inhibitors of receptor-interacting protein kinase 1
EP3552017B1 (en)	2016-12-09	2022-02-23	Denali Therapeutics Inc.	Compounds useful as ripk1 inhibitors
US10358441B2 (en)	2017-02-16	2019-07-23	Enanta Pharmaceuticals, Inc.	Processes for the preparation of benzodiazepine derivatives
US10752598B2 (en) *	2017-06-07	2020-08-25	Enanta Pharmaceuticals, Inc.	Aryldiazepine derivatives as RSV inhibitors
WO2019006295A1 (en)	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
WO2019006291A1 (en)	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
CA3077309A1 (en)	2017-09-29	2019-04-04	Enanta Pharmaceuticals, Inc.	Combination pharmaceutical agents as rsv inhibitors
WO2019094920A1 (en)	2017-11-13	2019-05-16	Enanta Pharmaceuticals, Inc.	Azepin-2-one derivatives as rsv inhibitors
WO2019199908A1 (en)	2018-04-11	2019-10-17	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as rsv inhibitors
US11254664B2 (en)	2019-03-18	2022-02-22	Enanta Pharmaceuticals, Inc.	Benzodiazepine derivatives as RSV inhibitors
WO2020210246A1 (en)	2019-04-09	2020-10-15	Enanta Pharmaceuticals, Inc,	Heterocyclic compounds as rsv inhibitors
US11505558B1 (en)	2019-10-04	2022-11-22	Enanta Pharmaceuticals, Inc.	Antiviral heterocyclic compounds
UY39032A (es)	2020-01-24	2021-07-30	Enanta Pharm Inc	Compuestos heterocíclicos como agentes antivirales
WO2022010882A1 (en)	2020-07-07	2022-01-13	Enanta Pharmaceuticals, Inc,	Dihydroquinoxaline and dihydropyridopyrazine derivatives as rsv inhibitors
US11945824B2 (en)	2020-10-19	2024-04-02	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as anti-viral agents
AU2023206890A1 (en)	2022-01-12	2024-08-22	Denali Therapeutics Inc.	Crystalline forms of (s)-5-benzyl-n-(5-methyl-4-oxo-2, 3,4,5- tetrahydropyrido [3,2-b] [l,4]oxazepin-3-yl)-4h-l,2,4-triazole-3-carboxamide

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2641280B1 (fr) *	1988-12-29	1994-01-21	Roussel Uclaf	Nouveaux derives de la 2,4-dioxo 2,3,4,5-tetrahydro 1h-1,5-benzodiazepine, leur procede de preparation et leur application comme medicaments
FR2659653B1 (fr) *	1990-03-13	1992-05-22	Rhone Poulenc Sante	Derives de l'uree, leur preparation et les medicaments les contenant.
US5206234A (en) *	1990-10-22	1993-04-27	Merck & Co., Inc.	Benzolactam analogs as antagonists of cck
JP2904941B2 (ja) *	1991-01-28	1999-06-14	出光興産株式会社	スチレン系重合体の精製方法
GEP20001968B (en) *	1992-01-21	2000-03-05	Glaxo Spa	Arilthio Compounds as Antibacterial and Antiviral Agents
NZ283929A (en) *	1994-04-14	1998-02-26	Glaxo Wellcome Inc	5-heterocyclic-1,5-benzodiazepine peptide analogs used to modulate effects of cck or gastrin

1993
- 1993-04-15 GB GB939307833A patent/GB9307833D0/en active Pending
1994
- 1994-01-04 US US08/525,659 patent/US5646140A/en not_active Expired - Lifetime
- 1994-04-11 IS IS4147A patent/IS4147A/is unknown
- 1994-04-11 IS IS4148A patent/IS4148A/is unknown
- 1994-04-12 MY MYPI94000884A patent/MY131569A/en unknown
- 1994-04-12 EC EC1994001066A patent/ECSP941066A/es unknown
- 1994-04-12 MY MYPI94000880A patent/MY112237A/en unknown
- 1994-04-13 IL IL10931694A patent/IL109316A/en not_active IP Right Cessation
- 1994-04-13 PE PE1994240028A patent/PE50594A1/es not_active Application Discontinuation
- 1994-04-13 PE PE1994240027A patent/PE50994A1/es not_active Application Discontinuation
- 1994-04-13 IL IL10931594A patent/IL109315A0/xx unknown
- 1994-04-13 US US08/522,363 patent/US5585376A/en not_active Expired - Fee Related
- 1994-04-13 AP APAP/P/1994/000635A patent/AP512A/en active
- 1994-04-13 AP APAP/P/1994/000634A patent/AP462A/en active
- 1994-04-14 WO PCT/EP1994/001131 patent/WO1994024149A1/en active IP Right Grant
- 1994-04-14 EP EP94913580A patent/EP0694039B1/en not_active Expired - Lifetime
- 1994-04-14 ES ES94913580T patent/ES2154674T3/es not_active Expired - Lifetime
- 1994-04-14 AU AU65676/94A patent/AU681139B2/en not_active Ceased
- 1994-04-14 PT PT94913580T patent/PT694039E/pt unknown
- 1994-04-14 ZA ZA942570A patent/ZA942570B/xx unknown
- 1994-04-14 SK SK1253-95A patent/SK281211B6/sk unknown
- 1994-04-14 DE DE69426624T patent/DE69426624T2/de not_active Expired - Lifetime
- 1994-04-14 CZ CZ19952675A patent/CZ286695B6/cs not_active IP Right Cessation
- 1994-04-14 PH PH48093A patent/PH30897A/en unknown
- 1994-04-14 DK DK94913580T patent/DK0694039T3/da active
- 1994-04-14 AT AT94913580T patent/ATE198894T1/de not_active IP Right Cessation
- 1994-04-14 ZA ZA942571A patent/ZA942571B/xx unknown
- 1994-04-14 RU RU95117974A patent/RU2135486C1/ru not_active IP Right Cessation
- 1994-04-14 CN CN94191773A patent/CN1058487C/zh not_active Expired - Fee Related
- 1994-04-14 HU HU9502978A patent/HU223467B1/hu not_active IP Right Cessation
- 1994-04-14 CA CA002158973A patent/CA2158973C/en not_active Expired - Fee Related
- 1994-04-14 PL PL94311084A patent/PL178790B1/pl unknown
- 1994-04-14 KR KR1019950704491A patent/KR100364948B1/ko not_active IP Right Cessation
- 1994-04-14 JP JP52273494A patent/JP3406317B2/ja not_active Expired - Fee Related
- 1994-04-14 NZ NZ265272A patent/NZ265272A/en not_active IP Right Cessation
- 1994-05-26 TW TW083104772A patent/TW487703B/zh not_active IP Right Cessation
1995
- 1995-10-12 FI FI954853A patent/FI954853A0/fi unknown
- 1995-10-12 OA OA60722A patent/OA10355A/en unknown
- 1995-10-13 NO NO19954090A patent/NO311133B1/no unknown
1998
- 1998-04-16 HK HK98103188A patent/HK1003943A1/xx not_active IP Right Cessation
2001
- 2001-03-27 GR GR20010400488T patent/GR3035641T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
IS4148A (is)	1994-10-16
IS4147A (is)	1994-10-16
JP3406317B2 (ja)	2003-05-12
NO954090D0 (no)	1995-10-13
IL109316A0 (en)	1994-07-31
GB9307833D0 (en)	1993-06-02
CN1058487C (zh)	2000-11-15
OA10355A (en)	2001-10-19
CA2158973A1 (en)	1994-10-27
HU223467B1 (hu)	2004-07-28
SK125395A3 (en)	1996-06-05
ECSP941066A (es)	1994-11-16
PL178790B1 (pl)	2000-06-30
RU2135486C1 (ru)	1999-08-27
JPH08508744A (ja)	1996-09-17
ZA942571B (en)	1994-11-11
PE50994A1 (es)	1995-01-06
PT694039E (pt)	2001-06-29
ATE198894T1 (de)	2001-02-15
CZ286695B6 (en)	2000-06-14
EP0694039B1 (en)	2001-01-24
AP462A (en)	1996-02-19
DK0694039T3 (da)	2001-05-21
MY131569A (en)	2007-08-30
CZ267595A3 (en)	1996-04-17
EP0694039A1 (en)	1996-01-31
GR3035641T3 (en)	2001-06-29
IL109316A (en)	1999-03-12
MY112237A (en)	2001-05-31
PL311084A1 (en)	1996-02-05
AU681139B2 (en)	1997-08-21
KR100364948B1 (ko)	2003-03-29
AP9400634A0 (en)	1994-04-30
ZA942570B (en)	1994-11-11
PH30897A (en)	1997-12-23
AP512A (en)	1996-07-29
CA2158973C (en)	2006-06-06
DE69426624T2 (de)	2001-06-21
NO954090L (no)	1995-12-13
NZ265272A (en)	1997-07-27
WO1994024149A1 (en)	1994-10-27
AU6567694A (en)	1994-11-08
PE50594A1 (es)	1995-01-06
FI954853A (fi)	1995-10-12
FI954853A0 (fi)	1995-10-12
US5646140A (en)	1997-07-08
DE69426624D1 (de)	2001-03-01
HU9502978D0 (en)	1995-12-28
US5585376A (en)	1996-12-17
SK281211B6 (sk)	2001-01-18
HUT74102A (en)	1996-11-28
AP9400635A0 (en)	1994-04-30
CN1120843A (zh)	1996-04-17
ES2154674T3 (es)	2001-04-16
HK1003943A1 (en)	1998-11-13
IL109315A0 (en)	1994-07-31
TW487703B (en)	2002-05-21

Publication	Publication Date	Title
NO311133B1 (no)	2001-10-15	1,5-benzodiazepinderivater med CCK-antagonistisk eller agonistisk aktivitet, anvendelse derav, farmasöytisk preparat samtfremgangsmåte for fremstilling derav
US5795887A (en)	1998-08-18	Method of inducing cholecystokinin agonist activity using 1,4- Benzodiazepine compounds
AU679085B2 (en)	1997-06-19	Benzodiazepine analogs
JPH05255279A (ja)	1993-10-05	コレシストキニン拮抗薬
US5859007A (en)	1999-01-12	CCK or gastrin modulating benzo b! 1,4! diazepines derivatives
US5739129A (en)	1998-04-14	CCK or gastrin modulating 5-heterocyclic-1, 5 benzodiazepines
RU2152939C1 (ru)	2000-07-20	5-гетероцикло-1,5-бензодиазепины и их фармацевтически приемлемые соли
CA2065715A1 (en)	1992-10-11	Cholecystokinin antagonists
SK125495A3 (en)	1996-06-05	1,5-benzodiazepine derivatives, manufacturing process, their use and pharmaceutical compositions containing them
US5910495A (en)	1999-06-08	Use of 1,5-benzo b!1,4-diazepines to control gastric emptying