NO323605B1 - Nye tioksotetrahydropyrimidinon- og tiohydantoinderivater, preparater av disse, fremstillingsmetode og anvendelse derav for fremstilling av medikamenter for behandling av sykdommer - Google Patents

Nye tioksotetrahydropyrimidinon- og tiohydantoinderivater, preparater av disse, fremstillingsmetode og anvendelse derav for fremstilling av medikamenter for behandling av sykdommer Download PDF

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Publication number: NO323605B1
Authority: NO; Norway
Prior art keywords: general formula; syndrome; compound; fibrosis; diseases
Prior art date: 1999-07-30

Application number

NO20020463A

Other languages

English (en)

Norwegian (no)

Other versions

NO20020463L (no

NO20020463D0 (no

Inventor

Christophe Alain Thurieau

Lydie Francine Poitout

Valerie Brault

Original Assignee

Sod Conseils Rech Applic

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.)

1999-07-30

Filing date

2002-01-29

Publication date

2007-06-18

2002-01-29 Application filed by Sod Conseils Rech Applic filed Critical Sod Conseils Rech Applic

2002-01-29 Publication of NO20020463D0 publication Critical patent/NO20020463D0/no

2002-02-13 Publication of NO20020463L publication Critical patent/NO20020463L/no

2007-06-18 Publication of NO323605B1 publication Critical patent/NO323605B1/no

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
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NO20020463A 1999-07-30 2002-01-29 Nye tioksotetrahydropyrimidinon- og tiohydantoinderivater, preparater av disse, fremstillingsmetode og anvendelse derav for fremstilling av medikamenter for behandling av sykdommer NO323605B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR9909886A FR2796945B1 (fr)	1999-07-30	1999-07-30	Nouveaux derives d'hydantoines, de thiohydantoines, de pyrimidinediones et de thioxopyrimidinones, leurs procedes de preparation et leur application a titre de medicaments
PCT/FR2000/002164 WO2001009090A2 (fr)	1999-07-30	2000-07-28	Derives d'hydantoines, de thiohydantoines, de pyrimidinediones et de thioxopyrimidinoneses, leurs procedes de preparation et leur application a titre de medicaments

Publications (3)

Publication Number	Publication Date
NO20020463D0 NO20020463D0 (no)	2002-01-29
NO20020463L NO20020463L (no)	2002-02-13
NO323605B1 true NO323605B1 (no)	2007-06-18

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Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20020463A NO323605B1 (no)	1999-07-30	2002-01-29	Nye tioksotetrahydropyrimidinon- og tiohydantoinderivater, preparater av disse, fremstillingsmetode og anvendelse derav for fremstilling av medikamenter for behandling av sykdommer

Country Status (24)

Country	Link
US (3)	US6759415B1 (da)
EP (1)	EP1246807B1 (da)
JP (1)	JP2003518011A (da)
KR (1)	KR100712587B1 (da)
CN (1)	CN1177828C (da)
AR (1)	AR024939A1 (da)
AT (1)	ATE308525T1 (da)
AU (1)	AU779357B2 (da)
BR (1)	BR0012852A (da)
CA (1)	CA2380070C (da)
CZ (1)	CZ2002301A3 (da)
DE (1)	DE60023747T2 (da)
DK (1)	DK1246807T3 (da)
ES (1)	ES2252051T3 (da)
FR (1)	FR2796945B1 (da)
HK (1)	HK1052510B (da)
HU (1)	HUP0202989A3 (da)
IL (1)	IL147744A0 (da)
MX (1)	MXPA02001016A (da)
NO (1)	NO323605B1 (da)
NZ (1)	NZ516718A (da)
PL (1)	PL364726A1 (da)
RU (1)	RU2277093C2 (da)
WO (1)	WO2001009090A2 (da)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0011071D0 (en) *	2000-05-08	2000-06-28	Novartis Ag	Organic compounds
JP4711523B2 (ja) *	2001-02-13	2011-06-29	日本臓器製薬株式会社	低アルブミン血症改善剤
MXPA03012042A (es) *	2001-06-25	2006-05-22	Il Consorzio Ferrara Richerche	Composiciones farmaceuticas que inhiben la proliferacion de adenomas pituitarios y metodos de uso de las mismas.
FR2832710B1 (fr) *	2001-11-28	2004-09-03	Sod Conseils Rech Applic	Derives de 5-sulfanyl-4h-1,2,4-triazoles et leur utilisation en tant que medicaments
NZ533397A (en) *	2001-11-28	2005-12-23	Sod Conseils Rech Applic	5-sulphanyl-4H-1,2,4-triazole derivatives and their use as a medicament
US7189856B2 (en)	2001-12-28	2007-03-13	Gideon Shapiro	Non-peptide somatostatin receptor ligands
HRP20050053A2 (en) *	2002-09-19	2005-04-30	Solvay Pharmaceuticals B.V.	1 h-1,2,4-triazole-3-carboxamide derivatives as cannabinoid-cb1 receptor ligands
FR2850652B1 (fr) *	2003-01-31	2008-05-30	Aventis Pharma Sa	Nouveaux derives d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases
US7354933B2 (en) *	2003-01-31	2008-04-08	Aventis Pharma Sa	Cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
DE10325813B4 (de) *	2003-06-06	2007-12-20	Universitätsklinikum Freiburg	Prophylaxe und/oder Therapie bei der portalen Hypertonie
EP1621539A1 (en) *	2004-07-27	2006-02-01	Aventis Pharma S.A.	Heterocycle -substituted cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
EP1621536A1 (en) *	2004-07-27	2006-02-01	Aventis Pharma S.A.	Amino cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
EP1621535A1 (en) *	2004-07-27	2006-02-01	Aventis Pharma S.A.	Substituted cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
NZ564223A (en) *	2005-05-13	2011-03-31	Univ California	Diarylhydantoin compounds for treating hormone refractory prostate cancer
FR2896504B1 (fr) *	2006-01-23	2012-07-13	Aventis Pharma Sa	Nouveaux derives d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases
FR2896503B1 (fr) *	2006-01-23	2012-07-13	Aventis Pharma Sa	Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases
EP2061767B1 (de)	2006-08-08	2014-12-17	Sanofi	Arylaminoaryl-alkyl-substituierte Imidazolidin-2,4-dione, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittel und ihre Verwendung
US9277737B2 (en)	2006-09-21	2016-03-08	Probiodrug Ag	Mouse models carrying a knock-out mutation of the QPCTL-gene
EA016584B1 (ru)	2006-09-21	2012-06-29	Пробиодруг Аг	Новые гены, родственные гену глутаминилциклазы
US8889709B2 (en)	2006-09-21	2014-11-18	Probiodrug Ag	Use of isoQC inhibitors in the treatment and prevention of inflammatory diseases or conditions
US8710086B2 (en)	2009-04-09	2014-04-29	Medivation Technologies, Inc.	Substituted di-arylhydantoin and di-arylthiohydantoin compounds and methods of use thereof
CN103917529B (zh) *	2011-11-11	2016-08-17	辉瑞大药厂	2-硫代嘧啶酮类
US20170281641A1 (en) *	2014-09-03	2017-10-05	Genzyme Corporation	CYCLIC UREA COMPOUNDS AS TROPOMYOSIN-RELATED KINASE (TRK) iNHIBITORS
WO2022206742A1 (zh) *	2021-03-30	2022-10-06	苏州开拓药业股份有限公司	一种一步法合成乙内酰硫脲衍生物的方法

Family Cites Families (8)

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Publication number	Priority date	Publication date	Assignee	Title
FR2693461B1 (fr) *	1992-07-08	1994-09-02	Roussel Uclaf	Nouvelles phénylimidazolidines substituées, leur procédé de préparation, leur application comme médicaments et les compositions pharmaceutiques les renfermant.
WO1997043278A1 (en) *	1996-05-14	1997-11-20	Novo Nordisk A/S	Somatostatin agonists and antagonists
AU699728B2 (en) *	1996-09-24	1998-12-10	Taiho Pharmaceutical Co., Ltd.	Cancerous metastasis inhibitors containing uracil derivatives
US6025372A (en) *	1997-04-04	2000-02-15	Merck & Co., Inc.	Somatostatin agonists
EP1019050B1 (en)	1997-06-24	2002-03-20	Novo Nordisk A/S	Use of somatostatin agonists and antagonists for treating diseases related to the eye
DK1086086T3 (da) *	1998-06-12	2005-01-24	Sod Conseils Rech Applic	Imidazolylderivater og anvendelse deraf som somatostatinreceptorligander
HUP0302962A2 (hu)	1998-06-12	2003-12-29	Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S.	Béta-karbolinszármazékok, ezeket a vegyületeket tartalmazó gyógyászati készítmények és a vegyületek alkalmazása
PL345037A1 (en)	1998-06-16	2001-11-19	Sod Conseils Rech Applic	Cyclic somatostatin analogs

1999
- 1999-07-30 FR FR9909886A patent/FR2796945B1/fr not_active Expired - Fee Related
2000
- 2000-07-25 AR ARP000103851A patent/AR024939A1/es active IP Right Grant
- 2000-07-28 WO PCT/FR2000/002164 patent/WO2001009090A2/fr not_active Ceased
- 2000-07-28 HK HK03104848.3A patent/HK1052510B/zh not_active IP Right Cessation
- 2000-07-28 CZ CZ2002301A patent/CZ2002301A3/cs unknown
- 2000-07-28 MX MXPA02001016A patent/MXPA02001016A/es active IP Right Grant
- 2000-07-28 DK DK00958634T patent/DK1246807T3/da active
- 2000-07-28 AU AU70091/00A patent/AU779357B2/en not_active Ceased
- 2000-07-28 JP JP2001514294A patent/JP2003518011A/ja active Pending
- 2000-07-28 AT AT00958634T patent/ATE308525T1/de not_active IP Right Cessation
- 2000-07-28 CA CA2380070A patent/CA2380070C/fr not_active Expired - Fee Related
- 2000-07-28 KR KR1020027001224A patent/KR100712587B1/ko not_active Expired - Fee Related
- 2000-07-28 NZ NZ516718A patent/NZ516718A/xx not_active IP Right Cessation
- 2000-07-28 ES ES00958634T patent/ES2252051T3/es not_active Expired - Lifetime
- 2000-07-28 DE DE60023747T patent/DE60023747T2/de not_active Expired - Lifetime
- 2000-07-28 RU RU2002105024/04A patent/RU2277093C2/ru not_active IP Right Cessation
- 2000-07-28 BR BR0012852-0A patent/BR0012852A/pt not_active Application Discontinuation
- 2000-07-28 HU HU0202989A patent/HUP0202989A3/hu unknown
- 2000-07-28 CN CNB008110654A patent/CN1177828C/zh not_active Expired - Fee Related
- 2000-07-28 IL IL14774400A patent/IL147744A0/xx not_active IP Right Cessation
- 2000-07-28 PL PL00364726A patent/PL364726A1/xx not_active Application Discontinuation
- 2000-07-28 US US10/048,144 patent/US6759415B1/en not_active Expired - Fee Related
- 2000-07-28 EP EP00958634A patent/EP1246807B1/fr not_active Expired - Lifetime
2002
- 2002-01-29 NO NO20020463A patent/NO323605B1/no not_active IP Right Cessation
2004
- 2004-03-30 US US10/813,139 patent/US7199145B2/en not_active Expired - Fee Related
2006
- 2006-06-01 US US11/444,769 patent/US7332517B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HUP0202989A2 (hu)	2002-12-28
US7332517B2 (en)	2008-02-19
NO20020463L (no)	2002-02-13
NZ516718A (en)	2003-04-29
CN1399631A (zh)	2003-02-26
DE60023747D1 (de)	2005-12-08
AR024939A1 (es)	2002-10-30
KR100712587B1 (ko)	2007-05-02
EP1246807A2 (fr)	2002-10-09
BR0012852A (pt)	2002-04-30
FR2796945B1 (fr)	2002-06-28
FR2796945A1 (fr)	2001-02-02
AU779357B2 (en)	2005-01-20
NO20020463D0 (no)	2002-01-29
US20040209908A1 (en)	2004-10-21
CN1177828C (zh)	2004-12-01
US20070021420A1 (en)	2007-01-25
ES2252051T3 (es)	2006-05-16
DE60023747T2 (de)	2006-08-03
PL364726A1 (en)	2004-12-13
AU7009100A (en)	2001-02-19
US6759415B1 (en)	2004-07-06
CZ2002301A3 (cs)	2002-08-14
HK1052510B (zh)	2005-04-29
HK1052510A1 (en)	2003-09-19
JP2003518011A (ja)	2003-06-03
US7199145B2 (en)	2007-04-03
HUP0202989A3 (en)	2003-02-28
WO2001009090A2 (fr)	2001-02-08
KR20020025203A (ko)	2002-04-03
MXPA02001016A (es)	2002-08-12
DK1246807T3 (da)	2006-03-20
EP1246807B1 (fr)	2005-11-02
WO2001009090A3 (fr)	2002-08-08
ATE308525T1 (de)	2005-11-15
IL147744A0 (en)	2002-08-14
CA2380070A1 (fr)	2001-02-08
RU2277093C2 (ru)	2006-05-27
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Publication	Publication Date	Title
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JP2002053577A (ja)	2002-02-19	新規ｎ−トリアゾリルメチル−ピペラジン誘導体、その製造方法および中間生成物、および前記誘導体を含有する医薬品
CA2687303C (en)	2015-05-05	((phenyl)imidazolyl)methylheteroaryl compounds
EP4605398A1 (en)	2025-08-27	Bicyclic ferroportin inhibitors
HK1031873B (en)	2005-03-04	Imidazolyl derivatives and their use as somatostatin receptor ligands