NO312510B1 - Bifenylsulfonamid matriksmetalloproteinase-inhibitorer, anvendelse derav, samt farmasöytiske formuleringer omfattende dem - Google Patents

Bifenylsulfonamid matriksmetalloproteinase-inhibitorer, anvendelse derav, samt farmasöytiske formuleringer omfattende dem Download PDF

Info

Publication number: NO312510B1
Authority: NO; Norway
Prior art keywords: biphenyl; sulfonylamino; methyl; butyric acid; acid
Prior art date: 1996-05-17

Application number

NO19985326A

Other languages

English (en)

Norwegian (no)

Other versions

NO985326D0 (no

NO985326L (no

Inventor

Patrick Michael O'brien

Drago Robert Sliskovic

Original Assignee

Warner Lambert Co

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.)

1996-05-17

Filing date

1998-11-16

Publication date

2002-05-21

1998-11-16 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1998-11-16 Publication of NO985326D0 publication Critical patent/NO985326D0/no

1999-01-14 Publication of NO985326L publication Critical patent/NO985326L/no

2002-05-21 Publication of NO312510B1 publication Critical patent/NO312510B1/no

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 4
-1 their use Substances 0.000 title abstract description 12
SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 title description 9
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- 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
- A61P9/10—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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/42—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups

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Chemical & Material Sciences (AREA)
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Bioinformatics & Cheminformatics (AREA)
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Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
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Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Immunology (AREA)
Biomedical Technology (AREA)
Epidemiology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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NO19985326A 1996-05-17 1998-11-16 Bifenylsulfonamid matriksmetalloproteinase-inhibitorer, anvendelse derav, samt farmasöytiske formuleringer omfattende dem NO312510B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US1746096P	1996-05-17	1996-05-17
PCT/US1997/006801 WO1997044315A1 (en)	1996-05-17	1997-04-24	Biphenylsulfonamide matrix metalloproteinase inhibitors

Publications (3)

Publication Number	Publication Date
NO985326D0 NO985326D0 (no)	1998-11-16
NO985326L NO985326L (no)	1999-01-14
NO312510B1 true NO312510B1 (no)	2002-05-21

Family

ID=21782716

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19985326A NO312510B1 (no)	1996-05-17	1998-11-16	Bifenylsulfonamid matriksmetalloproteinase-inhibitorer, anvendelse derav, samt farmasöytiske formuleringer omfattende dem

Country Status (22)

Country	Link
EP (1)	EP0901466B1 (2)
JP (1)	JP2000511175A (2)
KR (1)	KR20000011095A (2)
CN (1)	CN1077885C (2)
AT (1)	ATE207891T1 (2)
BG (1)	BG63940B1 (2)
BR (1)	BR9710841A (2)
CA (1)	CA2253342A1 (2)
CZ (1)	CZ294063B6 (2)
DE (1)	DE69707865T2 (2)
DK (1)	DK0901466T3 (2)
EA (1)	EA001561B1 (2)
EE (1)	EE03965B1 (2)
ES (1)	ES2167733T3 (2)
IL (1)	IL126832A0 (2)
NO (1)	NO312510B1 (2)
NZ (1)	NZ332711A (2)
PL (1)	PL186416B1 (2)
PT (1)	PT901466E (2)
SK (1)	SK282863B6 (2)
WO (1)	WO1997044315A1 (2)
ZA (1)	ZA974223B (2)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ288299A (en) *	1994-06-22	1998-06-26	British Biotech Pharm	Substituted (hetero)aryl-sulphonylaminomethyl-hydroxamic acid and medicaments
US6124333A (en) *	1995-06-22	2000-09-26	British Biotech Pharmaceuticals Limited	Metalloproteinase inhibitors
EP1028716A1 (en) *	1996-12-09	2000-08-23	Warner-Lambert Company	Method for treating and preventing heart failure and ventricular dilatation
AU737117B2 (en) *	1996-12-17	2001-08-09	Warner-Lambert Company	Use of matrix metalloproteinase inhibitors for treating neurological disorders and promoting wound healing
EP1366765A1 (en) *	1996-12-17	2003-12-03	Warner-Lambert Company Llc	Use of matrix metalloproteinase inhibitors for treating neurological disorders and promoting wound healing
GB9706255D0 (en) *	1997-03-26	1997-05-14	Smithkline Beecham Plc	Novel compounds
DE19719621A1 (de) *	1997-05-09	1998-11-12	Hoechst Ag	Sulfonylaminocarbonsäuren
SK262000A3 (en) *	1997-07-22	2001-01-18	Shionogi & Co	Therapeutic or prophylactic agent for glomerulopathy
KR20010033473A (ko) *	1997-12-23	2001-04-25	로즈 암스트롱, 크리스틴 에이. 트러트웨인	Ａｃｅ 저해제-ｍｍｐ 저해제의 병용 제제
US6410580B1 (en)	1998-02-04	2002-06-25	Novartis Ag	Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases
EP1053226A1 (en) *	1998-02-04	2000-11-22	Novartis AG	Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases
NZ505994A (en) *	1998-03-17	2003-10-31	Warner Lambert Co	Statin-matrix metalloproteinase inhibitor combinations useful fro treating vascular diseases
EP0967201A1 (en) *	1998-05-20	1999-12-29	Roche Diagnostics GmbH	Pharmaceutical agents containing sulfonamids as matrix metalloproteinase inhibitors
CA2337828C (en) *	1998-07-16	2010-08-17	Aventis Pharma Deutschland Gmbh	Phosphinic and phosphonic acid derivatives used as pharmaceuticals
BR9912296A (pt) *	1998-07-21	2001-04-17	Warner Lambert Co	Co-adminiostração de inibidores acat e mmp para o tratamento de lesões ateroscleróticas
DE19851184A1 (de) *	1998-11-06	2000-05-11	Aventis Pharma Gmbh	N-Arylsulfonyl-aminosäure-omega-amide
US6858598B1 (en)	1998-12-23	2005-02-22	G. D. Searle & Co.	Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6495578B1 (en) *	1999-04-19	2002-12-17	Shionogi & Co., Ltd.	Sulfonamide derivatives having oxadiazole rings
GB9918684D0 (en)	1999-08-09	1999-10-13	Novartis Ag	Organic compounds
WO2001037826A1 (en)	1999-11-26	2001-05-31	Shionogi & Co., Ltd.	Npyy5 antagonists
CA2423885A1 (en) *	2000-09-29	2003-03-27	Shionogi & Co., Ltd.	Thiazole and oxazole derivatives
GB0103303D0 (en)	2001-02-09	2001-03-28	Novartis Ag	Organic compounds
MXPA01013326A (es)	2001-02-14	2002-08-26	Warner Lambert Co	Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz.
WO2003035610A1 (en) *	2001-10-26	2003-05-01	Shionogi & Co., Ltd.	Sulfonamide derivative having mmp inhibitory activity
GB0314488D0 (en) *	2003-06-20	2003-07-23	Glaxo Group Ltd	Therapeutically useful compounds
EP1689716A1 (en) *	2003-12-04	2006-08-16	Wyeth	Biaryl sulfonamides and methods for using same
DE602005017879D1 (de) *	2004-03-22	2010-01-07	Southern Res Inst	Nichtpeptidinhibitoren von matrixmetalloproteinasen
CN101279956B (zh) *	2008-04-25	2011-06-15	南昌大学	一种基质金属蛋白酶抑制剂及合成方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5506242A (en) *	1993-01-06	1996-04-09	Ciba-Geigy Corporation	Arylsufonamido-substituted hydroxamic acids
NZ288299A (en) *	1994-06-22	1998-06-26	British Biotech Pharm	Substituted (hetero)aryl-sulphonylaminomethyl-hydroxamic acid and medicaments

1997
- 1997-04-24 AT AT97918788T patent/ATE207891T1/de not_active IP Right Cessation
- 1997-04-24 PL PL97329929A patent/PL186416B1/pl not_active IP Right Cessation
- 1997-04-24 EE EE9800397A patent/EE03965B1/xx not_active IP Right Cessation
- 1997-04-24 SK SK1577-98A patent/SK282863B6/sk unknown
- 1997-04-24 BR BR9710841A patent/BR9710841A/pt not_active IP Right Cessation
- 1997-04-24 WO PCT/US1997/006801 patent/WO1997044315A1/en not_active Ceased
- 1997-04-24 NZ NZ332711A patent/NZ332711A/en unknown
- 1997-04-24 EP EP97918788A patent/EP0901466B1/en not_active Expired - Lifetime
- 1997-04-24 JP JP09542377A patent/JP2000511175A/ja not_active Abandoned
- 1997-04-24 ES ES97918788T patent/ES2167733T3/es not_active Expired - Lifetime
- 1997-04-24 KR KR1019980709253A patent/KR20000011095A/ko not_active Ceased
- 1997-04-24 EA EA199800988A patent/EA001561B1/ru not_active IP Right Cessation
- 1997-04-24 CN CN97194719A patent/CN1077885C/zh not_active Expired - Fee Related
- 1997-04-24 PT PT97918788T patent/PT901466E/pt unknown
- 1997-04-24 IL IL12683297A patent/IL126832A0/xx unknown
- 1997-04-24 DE DE69707865T patent/DE69707865T2/de not_active Expired - Fee Related
- 1997-04-24 CZ CZ19983668A patent/CZ294063B6/cs not_active IP Right Cessation
- 1997-04-24 CA CA002253342A patent/CA2253342A1/en not_active Abandoned
- 1997-04-24 DK DK97918788T patent/DK0901466T3/da active
- 1997-05-15 ZA ZA9704223A patent/ZA974223B/xx unknown
1998
- 1998-11-12 BG BG102918A patent/BG63940B1/bg unknown
- 1998-11-16 NO NO19985326A patent/NO312510B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
IL126832A0 (en)	1999-08-17
PL186416B1 (pl)	2004-01-30
AU2680397A (en)	1997-12-09
NO985326D0 (no)	1998-11-16
BR9710841A (pt)	1999-08-17
HK1019585A1 (en)	2000-02-18
NO985326L (no)	1999-01-14
PT901466E (pt)	2002-04-29
AU713286B2 (en)	1999-11-25
EA199800988A1 (ru)	1999-04-29
ATE207891T1 (de)	2001-11-15
PL329929A1 (en)	1999-04-26
NZ332711A (en)	2000-06-23
JP2000511175A (ja)	2000-08-29
KR20000011095A (ko)	2000-02-25
ZA974223B (en)	1997-12-10
EA001561B1 (ru)	2001-04-23
CN1219166A (zh)	1999-06-09
DK0901466T3 (da)	2002-02-18
EP0901466A1 (en)	1999-03-17
EE9800397A (et)	1999-06-15
WO1997044315A1 (en)	1997-11-27
CZ294063B6 (cs)	2004-09-15
CZ366898A3 (cs)	1999-02-17
BG63940B1 (bg)	2003-07-31
SK282863B6 (sk)	2002-12-03
ES2167733T3 (es)	2002-05-16
EE03965B1 (et)	2003-02-17
DE69707865D1 (de)	2001-12-06
CA2253342A1 (en)	1997-11-27
DE69707865T2 (de)	2002-05-02
EP0901466B1 (en)	2001-10-31
SK157798A3 (en)	1999-04-13
CN1077885C (zh)	2002-01-16
BG102918A (en)	1999-09-30

Legal Events

Date	Code	Title	Description
2005-11-28	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
EP0901466B1 (en)	2001-10-31	Biphenylsulfonamide matrix metalloproteinase inhibitors
EP0934267B1 (en)	2002-01-30	Alpha-amino sulfonyl hydroxamic acids as matrix metalloproteinase inhibitors
AU705439B2 (en)	1999-05-20	Matrix metalloprotease inhibitors
EP0877737B1 (fr)	2001-08-01	Nouveaux derives de n-(arylsulfonyl)aminoacides ayant une affinite pour les recepteurs de la bradykinine
US5756545A (en)	1998-05-26	Biphenysulfonamide matrix metal alloproteinase inhibitors
NO177700B (no)	1995-07-31	Analogifremgangsmåte for fremstilling av terapeutisk aktive, hydroksaminsyrebaserte kollagenaseinhibitorforbindelser, samt mellomprodukter til anvendelse i framgangsmåten
JPH11501910A (ja)	1999-02-16	アリールスルホニルアミノヒドロキサム酸誘導体
WO1997030971A1 (en)	1997-08-28	M-AMIDINO PHENYL ANALOGS AS FACTOR Xa INHIBITORS
KR101493717B1 (ko)	2015-02-16	알킬아민 유도체
NO312893B1 (no)	2002-07-15	<beta>-sulfonylhydroksaminsyrer som matriksmetalloproteinaseinhibitorer, og farmasöytisk preparatinneholdende disse
US20040002493A1 (en)	2004-01-01	Benzoic acid derivatives and pharmaceutical agents comprising the same as active ingredient
JP2003505367A (ja)	2003-02-12	マトリックスメタロプロテイナーゼ阻害剤としての３−アリールスルホニル−２−（置換メチル）プロパン酸誘導体
US6727266B2 (en)	2004-04-27	Substituted tryptophan derivatives
AU713286C (en)	2000-09-28	Biphenylsulfonamide matrix metalloproteinase inhibitors
US5942544A (en)	1999-08-24	α-branched anilines, toluenes, and analogs thereof as factor Xa inhibitors
KR20010089617A (ko)	2001-10-06	아세틸렌계 베타-설폰아미도 및 포스핀산 아미드하이드록삼산 티에이씨이 억제제
MXPA98009083A (en)	1999-04-06	Metaloproteinase inhibitors with bifenilsulfonam matrix
KR0163668B1 (ko)	1999-01-15	비펩티드성 트롬빈억제제 및 그의 제조방법
KR0163669B1 (ko)	1999-01-15	선택적 트롬빈 억제제 및 그의 제조방법
KR20010101731A (ko)	2001-11-14	헤테로아릴 아세틸렌계 설폰아미드 및 포스핀산 아미드하이드록삼산 티에이씨이 억제제
KR20100043311A (ko)	2010-04-29	신규한 4-아릴-4-옥소부탄산 아미드 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 약학적 조성물
NO313325B1 (no)	2002-09-16	Nitrometyltiobenzenderivater, fremgangsmåter for fremstilling derav, farmasöytisk preparat og anvendelse av forbindelsene tilfremstilling av et medisinsk produkt
EP0375557A1 (en)	1990-06-27	Glycine derivative process for preparation thereof, and pharmaceutical composition containing it