NO322460B1 - Heteropolysykliske forbindelser og deres anvendelse som metabotropiske glutamatreseptorantagonister - Google Patents

Heteropolysykliske forbindelser og deres anvendelse som metabotropiske glutamatreseptorantagonister Download PDF

Info

Publication number: NO322460B1
Authority: NO; Norway
Prior art keywords: pyridyl; oxazole; oxadiazole; cyanophenyl; chloro
Prior art date: 1999-08-19

Application number

NO20020823A

Other languages

English (en)

Norwegian (no)

Other versions

NO20020823D0 (no

NO20020823L (no

Inventor

Bradford C Van Wagenen

Daryl L Smith

Susan M Sheehan

Donald A Mcleod

Thomas M Stormann

Scott T Moe

Abdelmalik Slassi

Methvin Benjamin Isaac

Original Assignee

Nps Pharma 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.)

1999-08-19

Filing date

2002-02-19

Publication date

2006-10-09

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22530400&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO322460(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2002-02-19 Application filed by Nps Pharma Inc filed Critical Nps Pharma Inc

2002-02-19 Publication of NO20020823D0 publication Critical patent/NO20020823D0/no

2002-04-17 Publication of NO20020823L publication Critical patent/NO20020823L/no

2006-10-09 Publication of NO322460B1 publication Critical patent/NO322460B1/no

Links

102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims abstract description 56
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Classifications

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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Health & Medical Sciences (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Hematology (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Thiazole And Isothizaole Compounds (AREA)

NO20020823A 1999-08-19 2002-02-19 Heteropolysykliske forbindelser og deres anvendelse som metabotropiske glutamatreseptorantagonister NO322460B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US14946499P	1999-08-19	1999-08-19
PCT/US2000/022618 WO2001012627A1 (en)	1999-08-19	2000-08-18	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists

Publications (3)

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NO20020823D0 NO20020823D0 (no)	2002-02-19
NO20020823L NO20020823L (no)	2002-04-17
NO322460B1 true NO322460B1 (no)	2006-10-09

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EP (1)	EP1210344B1 (de)
JP (2)	JP3790472B2 (de)
KR (1)	KR100875222B1 (de)
CN (1)	CN1313465C (de)
AT (1)	ATE307129T1 (de)
AU (1)	AU780191B2 (de)
BG (1)	BG65586B1 (de)
BR (1)	BR0013427A (de)
CA (1)	CA2381975A1 (de)
CY (1)	CY1105253T1 (de)
CZ (1)	CZ2002599A3 (de)
DE (1)	DE60023318T2 (de)
DK (1)	DK1210344T3 (de)
EE (1)	EE200200079A (de)
ES (1)	ES2250177T3 (de)
HU (1)	HUP0202757A3 (de)
IL (2)	IL148157A0 (de)
IS (1)	IS6275A (de)
MX (1)	MXPA02001764A (de)
NO (1)	NO322460B1 (de)
NZ (1)	NZ517221A (de)
PL (1)	PL353825A1 (de)
RU (1)	RU2296127C9 (de)
SK (1)	SK2512002A3 (de)
UA (1)	UA75871C2 (de)
WO (1)	WO2001012627A1 (de)
ZA (1)	ZA200201358B (de)

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6660753B2 (en)	1999-08-19	2003-12-09	Nps Pharmaceuticals, Inc.	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
CA2438991C (en) *	2001-02-21	2010-08-17	Nps Pharmaceuticals, Inc.	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
US6916821B2 (en)	2001-04-02	2005-07-12	Brown University	Methods of treating disorders with Group I mGluR antagonists
WO2002078745A2 (en) *	2001-04-02	2002-10-10	Brown University Research Foundation	Use of mglur5 antagonists in the manufacture of a medicament in the treatment of autism, mental retardation, schizophrenia
ES2295441T3 (es) *	2001-12-18	2008-04-16	MERCK & CO., INC.	Moduladores de pirazol heteroaril sustituido de receptor 5 metabotropico de glutamato.
EP1458708B1 (de) *	2001-12-18	2007-09-26	Merck & Co., Inc.	Heteroarylsubstituierte triazolmodulatoren des metabotropen glutamatarezeptors 5
EP1458385A4 (de) *	2001-12-19	2005-12-21	Merck & Co Inc	Heteroaryl-substituierte imidazol-modulatoren des metabotropen glutamat-rezeptors-5
ATE486600T1 (de) *	2002-03-12	2010-11-15	Merck Sharp & Dohme	Di-aryl-substituierte tetrazol-modulatoren des metabotropen glutamat-rezeptors-5
US7964609B2 (en)	2002-06-20	2011-06-21	Astrazeneca Ab	Use of mGluR5 antagonists for the treatment of gerd
SE0201943D0 (sv) *	2002-06-20	2002-06-20	Astrazeneca Ab	New use
AR040847A1 (es)	2002-08-09	2005-04-20	Astrazeneca Ab	1,2,4-oxadiazoles como moduladores de receptores de glutamato metabotropicos, para el tratamiento de desordenes neurologicos y psiquiatricos
WO2004014902A2 (en) *	2002-08-09	2004-02-19	Astrazeneca Ab	Compounds having an activity at metabotropic glutamate receptors
TW200424183A (en) *	2002-08-09	2004-11-16	Nps Pharma Inc	New compounds
GB0303503D0 (en) *	2003-02-14	2003-03-19	Novartis Ag	Organic compounds
AU2004227833B2 (en) *	2003-04-04	2009-10-01	Merck & Co., Inc.	Di-aryl substituted triazole modulators of metabotropic glutamate receptor-5
CA2524867A1 (en) *	2003-05-15	2004-12-02	Merck & Co., Inc.	3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as s1p receptor agonists
WO2005060961A2 (en) *	2003-12-18	2005-07-07	Astrazeneca Ab	Treatment of transient lower esophageal sphincter relaxations (tlesrs) and gastro-esophageal reflux disease (gerd)
BRPI0418149A (pt)	2003-12-24	2007-04-17	Prosidion Ltd	derivados heterocìclicos como agonistas do receptor de gprc
AU2005214378A1 (en) *	2004-02-18	2005-09-01	Astrazeneca Ab	Polyheterocyclic compounds and their use as metabotropic glutamate receptor antagonists
US20070185095A1 (en) *	2004-02-18	2007-08-09	Astrazeneca Ab	Fused heterocyclic compounds and their use as metabotropic glutamate receptor antagonists
US7585881B2 (en) *	2004-02-18	2009-09-08	Astrazeneca Ab	Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
TW200538108A (en)	2004-02-19	2005-12-01	Astrazeneca Ab	Fused heterocyclic compounds and their use as metabotropic glutamate receptor antagonists
WO2006004142A1 (ja) *	2004-06-30	2006-01-12	Banyu Pharmaceutical Co., Ltd.	ビアリール誘導体
KR100621192B1 (ko) *	2004-10-13	2006-09-19	한국화학연구원	무스카린 수용체 작용물질로서 작용하는1,2,3,4-테트라하이드로피리미디닐-1,2,4-옥사다이아졸유도체와 이의 제조방법
JP4557685B2 (ja)	2004-11-15	2010-10-06	独立行政法人理化学研究所	蛍光蛋白質
CA2593439C (en)	2005-01-14	2014-02-25	F. Hoffmann-La Roche Ag	Thiazole-4-carboxamide derivatives as mglur5 antagonists
GB0510142D0 (en) *	2005-05-18	2005-06-22	Addex Pharmaceuticals Sa	Novel compounds A1
EP1896011A1 (de) *	2005-06-28	2008-03-12	AstraZeneca AB	Neue verwendung
AU2006272978B2 (en)	2005-07-26	2012-06-07	Bial - Portela & Ca, S.A.	Nitrocatechol derivatives as COMT inhibitors
AR058807A1 (es)	2005-09-29	2008-02-27	Astrazeneca Ab	5-(fenilisoxazoletoxi)-triazol-3-il piridinas sustituidas, para el tratamiento de trastornos mediados por el receptor mglur5
JP5015166B2 (ja)	2005-11-08	2012-08-29	エフ．ホフマン−ラロシュアーゲー	ｍＧｌｕ５受容体アンタゴニストとしてのチアゾロ［４，５−ｃ］ピリジン誘導体
US7951824B2 (en)	2006-02-17	2011-05-31	Hoffman-La Roche Inc.	4-aryl-pyridine-2-carboxyamide derivatives
MX2008012738A (es) *	2006-04-03	2009-02-06	Astellas Pharma Inc	Heterocompuesto.
EP1845097A1 (de)	2006-04-10	2007-10-17	Portela & Ca., S.A.	Oxadiazolderivate als COMT Inihibitoren
US20100234349A1 (en) *	2006-09-04	2010-09-16	Olsen Gunnar M	Pharmaceutical combinations of a nicotine receptor modulator and a cognitive enhancer
CL2007002593A1 (es)	2006-09-07	2008-06-13	Actelion Pharmaceuticals Ltd	Compuestos derivados de 4-heteroaril-piridina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como rechazo de organos transplantados, sindromes autoinmunes y cancer.
SI2069335T1 (sl)	2006-09-08	2013-04-30	Actelion Pharmaceuticals Ltd.	Derivati piridin-3-ila kot imunomodulacijska sredstva
EP2069318B1 (de)	2006-09-21	2012-09-12	Actelion Pharmaceuticals Ltd.	Phenylderivate und ihre verwendung als immunmodulatoren
CN101631548B (zh)	2007-01-31	2014-08-27	比艾尔-坡特拉有限公司	Comt抑制剂的单次药物剂量单元和药物组合物
JP2010521450A (ja)	2007-03-16	2010-06-24	アクテリオンファーマシューティカルズリミテッド	Ｓ１ｐ１／ｅｄｇ１受容体アゴニストとしてのアミノ−ピリジン誘導体
PL2195311T3 (pl)	2007-08-17	2011-08-31	Actelion Pharmaceuticals Ltd	Pochodne pirydynowe jako modulatory receptora S1P1/EDG1
JP2011502148A (ja)	2007-10-31	2011-01-20	メルク・シャープ・エンド・ドーム・コーポレイション	疼痛の治療用としてのｐ２ｘ３受容体アンタゴニスト
CN101970430B (zh)	2007-11-01	2013-05-08	埃科特莱茵药品有限公司	嘧啶衍生物
RS52270B (sr) *	2007-12-20	2012-10-31	Bayer Pharma Aktiengesellschaft	4-(4-cijano-2-tioaril)-dihidropirimidinon i njegova primena
CN101990433B (zh)	2008-02-07	2014-11-05	马萨诸塞眼科耳科诊所	提高Atoh1表达的化合物
BRPI0910288A2 (pt)	2008-03-07	2019-09-24	Actelion Pharmaceuticals Ltd	composto de derivados de aminometil benzeno, composição farmacêutica que compreende esse composto e uso do mesmo.
AU2009226221A1 (en)	2008-03-17	2009-09-24	Bial - Portela & Ca., S.A.	Crystal forms of 5- [3- (2, 5-dichloro-4, 6-dimethyl-1-oxy-pyridine-3-yl) [1,2,3] oxadiazol-5-yl] -3-nit robenzene-1, 2-diol
US8598209B2 (en)	2008-10-31	2013-12-03	Merck Sharp & Dohme Corp.	P2X3, receptor antagonists for treatment of pain
DE102009041242A1 (de)	2009-09-11	2011-12-15	Bayer Schering Pharma Aktiengesellschaft	Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung
DE102008057344A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Aminoalkyl-substituierte Aryl-Verbindungen und ihre Verwendung
DE102008057343A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Heterocyclisch substituierte Aryl-Verbindungen und ihre Verwendung
DE102009041241A1 (de)	2009-09-11	2011-08-04	Bayer Schering Pharma Aktiengesellschaft, 13353	Substituierte Aryl-Verbindungen und ihre Verwendung
DE102008057364A1 (de)	2008-11-14	2010-05-20	Bayer Schering Pharma Aktiengesellschaft	Substituierte Aryl-Verbindungen und ihre Verwendung
AU2010229142A1 (en)	2009-03-23	2011-10-13	Merck Sharp & Dohme Corp.	P2X3, receptor antagonists for treatment of pain
US8946231B2 (en)	2009-03-23	2015-02-03	Merck Sharp & Dohme Corp.	P2X3, receptor antagonists for treatment of pain
ES2660892T3 (es)	2009-03-23	2018-03-26	Merck Sharp & Dohme Corp.	Antagonistas del receptor P2X3 para el tratamiento del dolor
KR102023255B1 (ko)	2009-04-01	2019-09-19	바이알 - 포르텔라 앤드 씨에이 에스에이	니트로카테콜 유도체를 포함하는 제약 제제 및 그의 제조 방법
CA2758587A1 (en) *	2009-04-13	2010-10-21	Irm Llc	Compositions and methods for modulating retinol binding to retinol binding protein 4 (rbp4)
KR101409131B1 (ko)	2009-07-16	2014-06-17	액테리온 파마슈티칼 리미티드	피리딘-4-일 유도체
US20130058915A1 (en)	2010-03-02	2013-03-07	Children's Medica Center Corporation	Methods and compositions for treatment of angelman syndrome and autism spectrum disorders
SG191742A1 (en)	2011-01-19	2013-08-30	Actelion Pharmaceuticals Ltd	2-methoxy-pyridin-4-yl derivatives
US20140045900A1 (en)	2011-02-11	2014-02-13	Bial-Portela & Ca, S.A.	Administration regime for nitrocatechols
BR112014014341A2 (pt)	2011-12-13	2017-08-22	Bial Portela & Ca Sa	Intermediário metilado, seu método de preparação e seus usos, e composição farmacêutica
JP5946288B2 (ja) *	2012-02-24	2016-07-06	公立大学法人名古屋市立大学	新規ヒドロキサム酸誘導体及びその用途
UY35327A (es)	2013-02-15	2014-09-30	Monsanto Technology Llc	?4,5-dihidro-1,2,4-oxadiazoles disustituidos en 3,5 y composiciones y métodos para controlar plagas de nematodos?.
EP2853532B1 (de) *	2013-09-28	2020-12-09	Instytut Farmakologii Polskiej Akademii Nauk	1,2,4-Oxadiazoldrivate als allosterische Modulatoren von metabotropen Glutamatrezeptoren, die zur Gruppe-III gehören
WO2016083863A1 (en)	2014-11-28	2016-06-02	Bial - Portela & Ca, S.A.	Medicaments for slowing parkinson's disease
MY192358A (en)	2015-05-20	2022-08-17	Idorsia Pharmaceuticals Ltd	Crystalline form of the compound (s)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol
AU2016281346B2 (en)	2015-06-23	2020-01-02	Kissei Pharmaceutical Co., Ltd.	Pyrazole derivative, or pharmaceutically acceptable salt thereof
MX2018011765A (es) *	2016-03-30	2019-05-20	Sinntaxis AB	Moduladores alostéricos negativos del receptor 5 metabotrópico de glutamato (mglur5) para su uso en el tratamiento de daños cerebrales maduros.
ES2965174T3 (es) *	2018-04-12	2024-04-11	Bayer Ag	Derivados de N-(ciclopropilmetil)-5-(metilsulfonil)-n-{1-[1-(pirimidin-2-il)-1H-1,2,4-triazol-5-il]etil}heterociclilamida y compuestos similares como plaguicidas
KR102276327B1 (ko) *	2019-06-25	2021-07-12	연세대학교 산학협력단	신규 옥사다이아졸 화합물 및 이를 포함하는 당뇨 예방 또는 치료용 조성물
WO2021046183A1 (en) *	2019-09-05	2021-03-11	Trevena, Inc.	Methods of treating epilepsy using the same

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1149011B (de) *	1960-04-05	1963-05-22	Hoechst Ag	Verfahren zur Herstellung von 3, 5-disubstituierten 1, 2, 4-Oxdiazolen
US3647809A (en) *	1968-04-26	1972-03-07	Chinoin Gyogyszer Es Vegyeszet	Certain pyridyl-1 2 4-oxadiazole derivatives
US4003909A (en) *	1974-07-22	1977-01-18	E. R. Squibb & Sons, Inc.	[(1,2,4-Oxadiazol-3-yl)phenyl]carbamic or thiocarbamic acid esters
US4022901A (en) *	1975-03-05	1977-05-10	E. R. Squibb & Sons, Inc.	3-Pyridinyl-5-isothiocyanophenyl oxadiazoles
AU675484B2 (en) *	1993-03-24	1997-02-06	Neurosearch A/S	Benzimidazole compounds, their use and preparation
US5554630A (en) *	1993-03-24	1996-09-10	Neurosearch A/S	Benzimidazole compounds
WO1994022846A1 (en) *	1993-03-30	1994-10-13	Pfizer Inc.	Compounds enhancing antitumor activity of other cytotoxic agents
RU2135493C1 (ru) *	1995-04-21	1999-08-27	Нюросерч А/С	Производное бензимидазола, фармацевтический состав и способ модуляции гамка-рецепторного комплекса
WO1997003967A1 (en) *	1995-07-22	1997-02-06	Rhone-Poulenc Rorer Limited	Substituted aromatic compounds and their pharmaceutical use
DE19643037A1 (de) *	1996-10-18	1998-04-23	Boehringer Ingelheim Kg	Neue Oxadiazole, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel
WO1999026927A2 (en) *	1997-11-21	1999-06-03	Nps Pharmaceuticals, Inc.	Metabotropic glutamate receptor antagonists for treating central nervous system diseases

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RU2296127C2 (ru)	2007-03-27
NZ517221A (en)	2004-01-30
AU6782400A (en)	2001-03-13
CN1379775A (zh)	2002-11-13
BG106493A (en)	2003-01-31
ES2250177T3 (es)	2006-04-16
SK2512002A3 (en)	2002-07-02
NO20020823D0 (no)	2002-02-19
EP1210344A1 (de)	2002-06-05
EE200200079A (et)	2003-06-16
MXPA02001764A (es)	2004-03-19
HK1047929A1 (en)	2003-03-14
BR0013427A (pt)	2002-07-30
RU2296127C9 (ru)	2007-08-27
IS6275A (is)	2002-02-18
DE60023318T2 (de)	2006-07-20
UA75871C2 (en)	2006-06-15
CA2381975A1 (en)	2001-02-22
ZA200201358B (en)	2003-07-30
HUP0202757A3 (en)	2006-03-28
AU780191B2 (en)	2005-03-03
EP1210344B1 (de)	2005-10-19
JP3790472B2 (ja)	2006-06-28
JP2003507378A (ja)	2003-02-25
IL148157A (en)	2007-07-04
IL148157A0 (en)	2002-09-12
CY1105253T1 (el)	2010-03-03
HUP0202757A2 (hu)	2002-12-28
DK1210344T3 (da)	2006-03-06
BG65586B1 (bg)	2009-01-30
KR20020038731A (ko)	2002-05-23
KR100875222B1 (ko)	2008-12-19
NO20020823L (no)	2002-04-17
CZ2002599A3 (cs)	2002-06-12
WO2001012627A1 (en)	2001-02-22
ATE307129T1 (de)	2005-11-15
CN1313465C (zh)	2007-05-02
JP2006143746A (ja)	2006-06-08
DE60023318D1 (de)	2006-03-02
PL353825A1 (en)	2003-12-01

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Publication	Publication Date	Title
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JP2898256B2 (ja)	1999-05-31	特定の４−アリール−５−カルバモイル−１，４−ジヒドロピリジンを含む医薬組成物
US20060189661A1 (en)	2006-08-24	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
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HK1047929B (en)	2006-01-13	Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
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