BG62520B1 - Аналози на аргинина, притежаващи инхибираща активност върхуno-синтетазата - Google Patents

Аналози на аргинина, притежаващи инхибираща активност върхуno-синтетазата Download PDF

Info

Publication number: BG62520B1
Authority: BG; Bulgaria
Prior art keywords: general formula; compound; nitro group; hydrogen atom; atom
Prior art date: 1995-03-04

Application number

BG101942A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG101942A (bg

Inventor

Colette Broquet

Pierre-Etienne Chabrier De Lassauniere

Original Assignee

Societe De Conseils De Recherches Ltd

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.)

1995-03-04

Filing date

1997-10-03

Publication date

2000-01-31

1997-10-03 Application filed by Societe De Conseils De Recherches Ltd filed Critical Societe De Conseils De Recherches Ltd

1999-01-29 Publication of BG101942A publication Critical patent/BG101942A/xx

2000-01-31 Publication of BG62520B1 publication Critical patent/BG62520B1/bg

Links

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- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

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BG101942A 1995-03-04 1997-10-03 Аналози на аргинина, притежаващи инхибираща активност върхуno-синтетазата BG62520B1 (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9504350.1A GB9504350D0 (en)	1995-03-04	1995-03-04	Arginine derivatives
PCT/FR1996/000337 WO1996027593A1 (fr)	1995-03-04	1996-03-04	Analogues de l'arginine ayant une activite en tant qu'inhibiteurs de la no synthase

Publications (2)

Publication Number	Publication Date
BG101942A BG101942A (bg)	1999-01-29
BG62520B1 true BG62520B1 (bg)	2000-01-31

Family

ID=10770627

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG101942A BG62520B1 (bg)	1995-03-04	1997-10-03	Аналози на аргинина, притежаващи инхибираща активност върхуno-синтетазата

Country Status (19)

Country	Link
US (1)	US5972940A (de)
EP (1)	EP0813529B1 (de)
JP (1)	JP3496061B2 (de)
KR (1)	KR19980702738A (de)
CN (1)	CN1071328C (de)
AT (1)	ATE223907T1 (de)
AU (1)	AU700871B2 (de)
BG (1)	BG62520B1 (de)
CA (1)	CA2215476C (de)
CZ (1)	CZ290747B6 (de)
DE (1)	DE69623602T2 (de)
ES (1)	ES2182964T3 (de)
GB (1)	GB9504350D0 (de)
HU (1)	HUP9801200A3 (de)
NZ (1)	NZ303235A (de)
PL (1)	PL188916B1 (de)
RU (1)	RU2168493C2 (de)
SK (1)	SK282664B6 (de)
WO (1)	WO1996027593A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9504350D0 (en) *	1995-03-04	1995-04-26	Sod Conseils Rech Applic	Arginine derivatives
FR2808525A1 (fr) *	2000-05-05	2001-11-09	Sod Conseils Rech Applic	Nouveaux derives d'aminoacides et leur application a titre de medicaments
EP1296943A1 (de) *	2000-05-05	2003-04-02	Societe De Conseils De Recherches Et D'applications Scientifiques S.A. (S.C.R.A.S.)	Aminsäure-derivate und ihre verwendung als arzneimittel
FR2824825B1 (fr) *	2001-05-15	2005-05-06	Servier Lab	Nouveaux derives d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2006051314A2 (en) *	2004-11-12	2006-05-18	Ucl Business Plc	Guanidine derivatives as inhibitors of ddah
HU0800031D0 (en) *	2008-01-16	2008-03-28	Biotech Hungary Kutato Es Fejl	Method for stabilization of s-nitrosoglutathione and composition prepared by the same

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL165652C (nl) *	1973-08-13	1981-05-15	Mitsubishi Chem Ind	Werkwijze ter bereiding van een preparaat met anti- trombosewerking en/of diagnosticum voor trombine in bloed op basis van l-argininederivaten, het gevormde preparaat, het gevormde diagnosticum en werkwijze ter bereiding van l-argininederivaten.
US3978045A (en) *	1973-08-13	1976-08-31	Mitsubishi Chemical Industries Ltd.	N2 -dansyl-L-arginine derivatives, and the pharmaceutically acceptable acid addition salts thereof
US4133880A (en) *	1974-11-08	1979-01-09	Mitsubishi Chemical Industries Ltd.	N2 -Substituted-L-arginine derivatives and the pharmaceutically acceptable acid addition salts thereof
CA1106851A (en) *	1975-08-08	1981-08-11	Shosuke Okamoto	N.sup.2-substituted-l-arginine derivatives and the pharmaceutically acceptable acid addition salts thereof
US4585757A (en)	1984-07-27	1986-04-29	Texas Tech University Health Sciences Center	Hypotensive active peptides
US4687840A (en)	1986-02-11	1987-08-18	Texas Tech University Health Sciences Center	Hypotensive active peptides
DE4011505C2 (de) *	1990-04-10	1995-01-12	Sanol Arznei Schwarz Gmbh	Nitratoalkancarbonsäure-Derivate, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
US5028627A (en) *	1989-09-13	1991-07-02	Cornell Research Foundation, Inc.	Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor
GB8929076D0 (en) *	1989-12-22	1990-02-28	Scras	Treatment of shock by blocking agents of edrf effect or formation
GB9200114D0 (en) *	1992-01-04	1992-02-26	Scras	Dual inhibitors of no synthase and cyclooxygenase
US5281627A (en) *	1992-05-28	1994-01-25	Cornell Research Foundation, Inc.	Substituted arginines and substituted homoarginines and use thereof
GB9504350D0 (en) *	1995-03-04	1995-04-26	Sod Conseils Rech Applic	Arginine derivatives

1995
- 1995-03-04 GB GBGB9504350.1A patent/GB9504350D0/en active Pending
1996
- 1996-03-04 WO PCT/FR1996/000337 patent/WO1996027593A1/fr not_active Ceased
- 1996-03-04 CN CN96192885A patent/CN1071328C/zh not_active Expired - Fee Related
- 1996-03-04 AT AT96905907T patent/ATE223907T1/de not_active IP Right Cessation
- 1996-03-04 CA CA002215476A patent/CA2215476C/fr not_active Expired - Fee Related
- 1996-03-04 EP EP96905907A patent/EP0813529B1/de not_active Expired - Lifetime
- 1996-03-04 KR KR1019970706145A patent/KR19980702738A/ko not_active Ceased
- 1996-03-04 AU AU49479/96A patent/AU700871B2/en not_active Ceased
- 1996-03-04 US US08/913,455 patent/US5972940A/en not_active Expired - Fee Related
- 1996-03-04 NZ NZ303235A patent/NZ303235A/xx not_active IP Right Cessation
- 1996-03-04 JP JP52665796A patent/JP3496061B2/ja not_active Expired - Fee Related
- 1996-03-04 SK SK1121-97A patent/SK282664B6/sk not_active IP Right Cessation
- 1996-03-04 HU HU9801200A patent/HUP9801200A3/hu unknown
- 1996-03-04 CZ CZ19972687A patent/CZ290747B6/cs not_active IP Right Cessation
- 1996-03-04 ES ES96905907T patent/ES2182964T3/es not_active Expired - Lifetime
- 1996-03-04 PL PL96322069A patent/PL188916B1/pl not_active IP Right Cessation
- 1996-03-04 DE DE69623602T patent/DE69623602T2/de not_active Expired - Lifetime
- 1996-03-04 RU RU97116496/04A patent/RU2168493C2/ru not_active IP Right Cessation
1997
- 1997-10-03 BG BG101942A patent/BG62520B1/bg unknown

Also Published As

Publication number	Publication date
SK282664B6 (sk)	2002-11-06
HUP9801200A2 (hu)	1998-09-28
RU2168493C2 (ru)	2001-06-10
JPH11501043A (ja)	1999-01-26
US5972940A (en)	1999-10-26
DE69623602D1 (de)	2002-10-17
CN1179774A (zh)	1998-04-22
CZ290747B6 (cs)	2002-10-16
ES2182964T3 (es)	2003-03-16
JP3496061B2 (ja)	2004-02-09
PL188916B1 (pl)	2005-05-31
EP0813529B1 (de)	2002-09-11
GB9504350D0 (en)	1995-04-26
WO1996027593A1 (fr)	1996-09-12
CZ268797A3 (cs)	1998-07-15
NZ303235A (en)	1999-08-30
ATE223907T1 (de)	2002-09-15
CN1071328C (zh)	2001-09-19
HUP9801200A3 (en)	1998-12-28
CA2215476A1 (fr)	1996-09-12
DE69623602T2 (de)	2003-07-31
BG101942A (bg)	1999-01-29
HK1013777A1 (en)	1999-09-10
AU4947996A (en)	1996-09-23
AU700871B2 (en)	1999-01-14
KR19980702738A (ko)	1998-08-05
PL322069A1 (en)	1998-01-05
SK112197A3 (en)	1998-01-14
EP0813529A1 (de)	1997-12-29
CA2215476C (fr)	2006-08-15

Publication	Publication Date	Title
US6048899A (en)	2000-04-11	Anticonvulsant enantiomeric amino acid derivatives
Nishizawa et al.	1977	Synthesis and structure-activity relations of bestatin analogs, inhibitors of aminopeptidase B
Greenberg et al.	1984	Structure and dynamics of Troeger's base and simple derivatives in acidic media
FI80674C (fi)	1990-07-10	Foerfarande foer framstaellning av terapeutiskt aktivt (r)-alfa-etyl-2-oxo-1-pyrrolidinacetamid.
JPH06239822A (ja)	1994-08-30	新規なｎ−ベンゾイルアミノ酸誘導体、これらの化合物を含有する医薬組成物およびこれらの化合物を製造する方法
IT9021075A1 (it)	1992-01-26	Derivati acidi benzoici sostituiti ad attivita' cardiovascolare
ES2317496T3 (es)	2009-04-16	Derivados del trifluorometilbenzamida y los usos terapeuticos de los mismos.
SU1272982A3 (ru)	1986-11-23	Способ получени производных пролина или их фармацевтически приемлемых солей
RU2168493C2 (ru)	2001-06-10	Производные l-аргинина, способ их получения, фармацевтическая композиция, обладающая ингибирующей no-синтазу активностью
SU937450A1 (ru)	1982-06-23	N-замещенные лактамы, про вл ющие мнезическую, антигипоксическую и сердечную активность
AU624978B2 (en)	1992-06-25	N,n'-bis(alkoxyalkyl)-pyridine-2,4-dicarboxylic acid diamides, preparation and their use
DE69131835T2 (de)	2000-06-15	Methotrexatderivate mit antirheumatischer aktivität
EP0333000B1 (de)	1993-05-19	Peptide mit inhibitorischer Wirkung auf enzymatische Systeme, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
NO124430B (de)	1972-04-17
US4525476A (en)	1985-06-25	N-[1-oxo-3-(5-oxo-2-pyrrolidinyl)propyl]-alpha-aminoacids and derivatives as cognition activators
US4943561A (en)	1990-07-24	Gastrin releasing peptide antagonist
Ronwin	1953	Direct Acylation of α-Amino Acids and Dipeptides
US3300510A (en)	1967-01-24	Hydantoins
DeBernardis et al.	1988	Evaluation of the side arm of (naphthylvinyl) pyridinium inhibitors of choline acetyltransferase
ES2439322T3 (es)	2014-01-22	Derivados de amino alcohol y sus actividades terapéuticas
JPH0356486A (ja)	1991-03-12	健忘症治療剤
JPH0356462A (ja)	1991-03-12	ピログルタミン酸誘導体
BG62167B1 (bg)	1999-04-30	Производни на аскорбинова киселина,методи за тяхното получаване и приложение
EP1849766A1 (de)	2007-10-31	Beta-benzyloxyaspartamsäurederivat mit zwei substituenten am benzolring
IE41605B1 (en)	1980-02-13	A tetrapeptide amide and acid addition salts thereof