NO320809B1 - 4-heterocyklysulfonamidyl-6-metoksy-5-(2-metoksy-fenoksy)-2-pyridyl-pyrimidinderivater, farmasoytisk preparat og mellomprodukter, anvendelse og fremgangsmate for fremstilling av medikamenter - Google Patents

4-heterocyklysulfonamidyl-6-metoksy-5-(2-metoksy-fenoksy)-2-pyridyl-pyrimidinderivater, farmasoytisk preparat og mellomprodukter, anvendelse og fremgangsmate for fremstilling av medikamenter Download PDF

Info

Publication number: NO320809B1
Authority: NO; Norway
Prior art keywords: methoxy; pyridin; phenoxy; pyrimidin; amide
Prior art date: 1999-03-03

Application number

NO20014224A

Other languages

English (en)

Norwegian (no)

Other versions

NO20014224D0 (no

NO20014224L (no

Inventor

Volker Breu

Philippe Coassolo

Werner Neidhart

Sebastien Roux

Peter Weiss

Original Assignee

Hoffmann La Roche

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.)

1999-03-03

Filing date

2001-08-31

Publication date

2006-01-30

2001-08-31 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2001-08-31 Publication of NO20014224D0 publication Critical patent/NO20014224D0/no

2001-08-31 Publication of NO20014224L publication Critical patent/NO20014224L/no

2006-01-30 Publication of NO320809B1 publication Critical patent/NO320809B1/no

Links

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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
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Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
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Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Diabetes (AREA)
Hematology (AREA)
Pulmonology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Obesity (AREA)
Ophthalmology & Optometry (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Gynecology & Obstetrics (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Child & Adolescent Psychology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)

NO20014224A 1999-03-03 2001-08-31 4-heterocyklysulfonamidyl-6-metoksy-5-(2-metoksy-fenoksy)-2-pyridyl-pyrimidinderivater, farmasoytisk preparat og mellomprodukter, anvendelse og fremgangsmate for fremstilling av medikamenter NO320809B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP99104306		1999-03-03
PCT/EP2000/001660 WO2000052007A1 (fr)	1999-03-03	2000-02-28	Derives 4-heterocyclysulfonamidyl-6-methoxy-5-(2-methoxy-phenoxy)-2-pyridyl-pyrimidine, preparations et utilisations comme antagonistes du recepteur d'endotheline

Publications (3)

Publication Number	Publication Date
NO20014224D0 NO20014224D0 (no)	2001-08-31
NO20014224L NO20014224L (no)	2001-08-31
NO320809B1 true NO320809B1 (no)	2006-01-30

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NO20014224A NO320809B1 (no)	1999-03-03	2001-08-31	4-heterocyklysulfonamidyl-6-metoksy-5-(2-metoksy-fenoksy)-2-pyridyl-pyrimidinderivater, farmasoytisk preparat og mellomprodukter, anvendelse og fremgangsmate for fremstilling av medikamenter

Country Status (30)

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US (2)	US6417360B1 (fr)
EP (1)	EP1185525B1 (fr)
JP (1)	JP3488203B2 (fr)
KR (1)	KR100478798B1 (fr)
CN (1)	CN1342158B (fr)
AR (1)	AR044720A1 (fr)
AT (1)	ATE353325T1 (fr)
AU (1)	AU756738B2 (fr)
BR (1)	BR0008717A (fr)
CA (1)	CA2364906C (fr)
CY (1)	CY1108002T1 (fr)
CZ (1)	CZ300324B6 (fr)
DE (1)	DE60033280T2 (fr)
DK (1)	DK1185525T3 (fr)
ES (1)	ES2280198T3 (fr)
HK (1)	HK1044943B (fr)
HR (1)	HRP20010630B1 (fr)
HU (1)	HUP0200080A3 (fr)
ID (1)	ID30484A (fr)
IL (1)	IL145051A0 (fr)
MA (1)	MA26776A1 (fr)
NO (1)	NO320809B1 (fr)
NZ (1)	NZ513671A (fr)
PL (1)	PL198815B1 (fr)
PT (1)	PT1185525E (fr)
RS (1)	RS50109B (fr)
RU (1)	RU2201928C1 (fr)
TR (1)	TR200102562T2 (fr)
WO (1)	WO2000052007A1 (fr)
ZA (1)	ZA200107157B (fr)

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MY140724A (en)	2000-07-21	2010-01-15	Actelion Pharmaceuticals Ltd	Novel arylethene-sulfonamides
US20020184047A1 (en) *	2001-04-03	2002-12-05	Plotnick Michael A.	Universal ad queue
EP1454625A1 (fr) *	2003-03-06	2004-09-08	Speedel Development AG	Pyridylsulfonamidyl-pyrimidines pour le traitement des néphropaties diabétiques
EP1595880A1 (fr) *	2004-05-13	2005-11-16	Speedel Pharma AG	Formes crystallines d'un pyridinylsulphonamide et leur utilisation comme antagonistes du récepteur de l'endothéline
EP1924325A2 (fr) *	2005-09-12	2008-05-28	Speedel Pharma AG	Pyridylsulfonamidyl-pyrimidines utiles dans la prevention d'un rejet de greffe de vaisseau sanguin
WO2007119214A2 (fr) *	2006-04-13	2007-10-25	Actelion Pharmaceuticals Ltd	Traitement précoce de fibrose pulmonaire idiopathique
EP1938812A1 (fr) *	2006-12-22	2008-07-02	Speedel Pharma AG	Composition pharmaceutique utilisant aliskiren et avosentan
US20100093758A1 (en) *	2008-07-23	2010-04-15	Auspex Pharmaceuticals, Inc.	Pyridine sulfonamide modulators of endothelin-a receptor
WO2016123291A1 (fr)	2015-01-29	2016-08-04	Signal Pharmaceuticals, Llc	Isotopologues de 2-(tert-butylamino)-4-((1r,3r,4r) -3-hydroxy-4-méthylcyclohexylamino)-pyrimidine-5-carboxamide
KR101936054B1 (ko)	2017-06-23	2019-01-11	한국과학기술연구원	항염증 활성을 가지는 6-페녹시피리미딘 유도체, 이의 제조방법 및 이를 활성성분으로 하는 약학 조성물
KR20240121242A (ko)	2021-12-17	2024-08-08	넥세라 파마 씨오., 엘티디.	클라조센탄 디소듐 염, 이의 제조 및 이를 포함하는 약학 조성물

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GB8400354D0 (en) *	1984-01-07	1984-02-08	Pfizer Ltd	Therapeutic agents
FR2656610B1 (fr) *	1989-12-29	1992-05-07	Sanofi Sa	Derives d'amino-2 phenyl-4 thiazole, leur procede de preparation et leur application therapeutique.
CN1064965C (zh) *	1994-11-25	2001-04-25	弗·哈夫曼-拉罗切有限公司	新的磺酰胺类化合物及其作为药物的用途
US5837708A (en)	1994-11-25	1998-11-17	Hoffmann-La Roche Inc.	Sulphonamides
CA2162630C (fr)	1994-11-25	2007-05-01	Volker Breu	Sulfonamides
TW313568B (fr)	1994-12-20	1997-08-21	Hoffmann La Roche
ES2221696T3 (es)	1997-08-19	2005-01-01	F. Hoffmann-La Roche Ag	Procedimiento para la preparacion de piridinas 2,5.disustituidas.
TWI284642B (en) *	1999-01-18	2007-08-01	Hoffmann La Roche	Novel heterocyclic sulfonamides

2000
- 2000-02-17 US US09/505,548 patent/US6417360B1/en not_active Expired - Lifetime
- 2000-02-28 HK HK02106318.0A patent/HK1044943B/zh not_active IP Right Cessation
- 2000-02-28 TR TR2001/02562T patent/TR200102562T2/xx unknown
- 2000-02-28 DE DE60033280T patent/DE60033280T2/de not_active Expired - Lifetime
- 2000-02-28 PT PT00909263T patent/PT1185525E/pt unknown
- 2000-02-28 EP EP00909263A patent/EP1185525B1/fr not_active Expired - Lifetime
- 2000-02-28 PL PL351794A patent/PL198815B1/pl unknown
- 2000-02-28 IL IL14505100A patent/IL145051A0/xx not_active IP Right Cessation
- 2000-02-28 KR KR10-2001-7011184A patent/KR100478798B1/ko not_active Expired - Fee Related
- 2000-02-28 CA CA002364906A patent/CA2364906C/fr not_active Expired - Lifetime
- 2000-02-28 WO PCT/EP2000/001660 patent/WO2000052007A1/fr not_active Ceased
- 2000-02-28 JP JP2000602233A patent/JP3488203B2/ja not_active Expired - Lifetime
- 2000-02-28 ID IDW00200101897A patent/ID30484A/id unknown
- 2000-02-28 HR HR20010630A patent/HRP20010630B1/xx not_active IP Right Cessation
- 2000-02-28 CZ CZ20013108A patent/CZ300324B6/cs not_active IP Right Cessation
- 2000-02-28 CN CN008043582A patent/CN1342158B/zh not_active Expired - Lifetime
- 2000-02-28 NZ NZ513671A patent/NZ513671A/xx not_active IP Right Cessation
- 2000-02-28 BR BR0008717-3A patent/BR0008717A/pt not_active IP Right Cessation
- 2000-02-28 AT AT00909263T patent/ATE353325T1/de active
- 2000-02-28 RS YUP-628/01A patent/RS50109B/sr unknown
- 2000-02-28 ES ES00909263T patent/ES2280198T3/es not_active Expired - Lifetime
- 2000-02-28 DK DK00909263T patent/DK1185525T3/da active
- 2000-02-28 RU RU2001126348/04A patent/RU2201928C1/ru not_active IP Right Cessation
- 2000-02-28 HU HU0200080A patent/HUP0200080A3/hu unknown
- 2000-02-28 AU AU31611/00A patent/AU756738B2/en not_active Ceased
- 2000-03-02 AR ARP000100921A patent/AR044720A1/es active IP Right Grant
2001
- 2001-08-29 ZA ZA200107157A patent/ZA200107157B/en unknown
- 2001-08-31 NO NO20014224A patent/NO320809B1/no not_active IP Right Cessation
- 2001-09-03 MA MA26313A patent/MA26776A1/fr unknown
2002
- 2002-03-08 US US10/094,126 patent/US6521631B2/en not_active Expired - Lifetime
2007
- 2007-03-08 CY CY20071100324T patent/CY1108002T1/el unknown

Also Published As

Publication number	Publication date
KR100478798B1 (ko)	2005-03-24
WO2000052007A1 (fr)	2000-09-08
KR20010102480A (ko)	2001-11-15
ES2280198T3 (es)	2007-09-16
EP1185525B1 (fr)	2007-02-07
ZA200107157B (en)	2002-11-29
US20020137933A1 (en)	2002-09-26
PT1185525E (pt)	2007-05-31
CZ20013108A3 (cs)	2002-02-13
CY1108002T1 (el)	2013-09-04
HK1044943B (zh)	2013-03-22
EP1185525A1 (fr)	2002-03-13
JP2002538156A (ja)	2002-11-12
BR0008717A (pt)	2001-12-26
MA26776A1 (fr)	2004-12-20
CZ300324B6 (cs)	2009-04-22
RU2201928C1 (ru)	2003-04-10
NZ513671A (en)	2003-04-29
PL198815B1 (pl)	2008-07-31
DE60033280T2 (de)	2007-11-22
TR200102562T2 (tr)	2002-02-21
CN1342158B (zh)	2012-06-06
YU62801A (sh)	2004-07-15
HRP20010630B1 (hr)	2010-08-31
NO20014224D0 (no)	2001-08-31
AU3161100A (en)	2000-09-21
HUP0200080A3 (en)	2003-01-28
IL145051A0 (en)	2002-06-30
CA2364906A1 (fr)	2000-09-08
DK1185525T3 (da)	2007-06-04
US6417360B1 (en)	2002-07-09
HRP20010630A2 (en)	2002-08-31
DE60033280D1 (de)	2007-03-22
HUP0200080A2 (en)	2002-06-29
RS50109B (sr)	2009-03-25
HK1044943A1 (en)	2002-11-08
CN1342158A (zh)	2002-03-27
NO20014224L (no)	2001-08-31
ATE353325T1 (de)	2007-02-15
ID30484A (id)	2001-12-13
PL351794A1 (en)	2003-06-16
AR044720A1 (es)	2005-10-05
CA2364906C (fr)	2006-01-10
US6521631B2 (en)	2003-02-18
AU756738B2 (en)	2003-01-23
JP3488203B2 (ja)	2004-01-19
RU2001126348A (ru)	2004-03-20

Legal Events

Date	Code	Title	Description
2015-09-28	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
EP1149091B1 (fr)	2008-03-19	4-(heterocyclysulfonamido)-5-methoxy-6-(2-methoxyphenoxy)-2-phenyle ou pyridylpyrimidines faisant office d'antagonistes des recepteurs de l'endotheline
NO320809B1 (no)	2006-01-30	4-heterocyklysulfonamidyl-6-metoksy-5-(2-metoksy-fenoksy)-2-pyridyl-pyrimidinderivater, farmasoytisk preparat og mellomprodukter, anvendelse og fremgangsmate for fremstilling av medikamenter
JP2006509775A (ja)	2006-03-23	新規スルファミド類
JP4769418B2 (ja)	2011-09-07	新規なアルカンスルホンアミド類
MXPA01008783A (en)	2002-05-09	4-heterocyclysulfonamidyl -6-methoxy-5 -(2-methoxy-phenoxy) -2-pyridyl -pyrimidine derivatives, their preparation and use as endothelin receptor antagonists
EP1322624B1 (fr)	2009-10-21	Arylalcane-sulfonamides
TWI303245B (en)	2008-11-21	Novel sulfamides
MXPA01007242A (en)	2002-03-05	4-(heterocyclylsulfonamido) -5-methoxy-6- (2-methoxyphenoxy) -2-phenyl- or pyridylpyrimidines as endothelin receptor antagonists