NO315687B1 - Anvendelse av nebivolol for fremstilling av et anti-aterogent middel - Google Patents

Anvendelse av nebivolol for fremstilling av et anti-aterogent middel Download PDF

Info

Publication number: NO315687B1
Authority: NO; Norway
Prior art keywords: nebivolol; compound; vascular; formula; acid
Prior art date: 1994-12-28

Application number

NO19972980A

Other languages

English (en)

Norwegian (no)

Other versions

NO972980D0 (no

NO972980L (no

Inventor

Didier Robert Guy G Courcelles

Anne Simone Josephine Lesage

Josepha Eduarda Maria F Leysen

Original Assignee

Janssen Pharmaceutica Nv

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.)

1994-12-28

Filing date

1997-06-26

Publication date

2003-10-13

1997-06-26 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1997-06-26 Publication of NO972980D0 publication Critical patent/NO972980D0/no

1997-06-26 Publication of NO972980L publication Critical patent/NO972980L/no

2003-10-13 Publication of NO315687B1 publication Critical patent/NO315687B1/no

Links

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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- 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

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Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Epidemiology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Psychiatry (AREA)
Toxicology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicinal Preparation (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Pyrane Compounds (AREA)

NO19972980A 1994-12-28 1997-06-26 Anvendelse av nebivolol for fremstilling av et anti-aterogent middel NO315687B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP94203775		1994-12-28
PCT/EP1995/005174 WO1996019987A1 (fr)	1994-12-28	1995-12-21	Utilisation de nebivolol comme agent anti-atherogene

Publications (3)

Publication Number	Publication Date
NO972980D0 NO972980D0 (no)	1997-06-26
NO972980L NO972980L (no)	1997-06-26
NO315687B1 true NO315687B1 (no)	2003-10-13

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ID=8217503

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Application Number	Title	Priority Date	Filing Date
NO19972980A NO315687B1 (no)	1994-12-28	1997-06-26	Anvendelse av nebivolol for fremstilling av et anti-aterogent middel

Country Status (20)

Country	Link
US (2)	US5874461A (fr)
EP (1)	EP0801564B1 (fr)
JP (1)	JPH10511655A (fr)
KR (1)	KR100264348B1 (fr)
CN (1)	CN1167418C (fr)
AT (1)	ATE214924T1 (fr)
AU (1)	AU700364B2 (fr)
CA (1)	CA2207333C (fr)
CZ (1)	CZ287513B6 (fr)
DE (1)	DE69526120T2 (fr)
DK (1)	DK0801564T3 (fr)
ES (1)	ES2176354T3 (fr)
FI (1)	FI118884B (fr)
HU (1)	HU226208B1 (fr)
NO (1)	NO315687B1 (fr)
NZ (1)	NZ298074A (fr)
PT (1)	PT801564E (fr)
SI (1)	SI0801564T1 (fr)
SK (1)	SK282144B6 (fr)
WO (1)	WO1996019987A1 (fr)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU700364B2 (en) *	1994-12-28	1999-01-07	Janssen Pharmaceutica N.V.	Use of nebivolol as an anti-atherogenic
DE19716120A1 (de) *	1997-04-17	1998-10-22	Europ Lab Molekularbiolog	Verwendung von cholesterinsenkenden Mitteln
US6713651B1 (en)	1999-06-07	2004-03-30	Theravance, Inc.	β2-adrenergic receptor agonists
US6541669B1 (en)	1998-06-08	2003-04-01	Theravance, Inc.	β2-adrenergic receptor agonists
JP2000207219A (ja) *	1999-01-18	2000-07-28	Fujitsu Ten Ltd	車載端末とセンタ―との間の通信システム、及び、通信システムに使用する車載端末
US6683115B2 (en)	1999-06-02	2004-01-27	Theravance, Inc.	β2-adrenergic receptor agonists
US6593497B1 (en)	1999-06-02	2003-07-15	Theravance, Inc.	β2-adrenergic receptor agonists
UA73965C2 (en)	1999-12-08	2005-10-17	Theravance Inc	b2 ADRENERGIC RECEPTOR ANTAGONISTS
US6982251B2 (en)	2000-12-20	2006-01-03	Schering Corporation	Substituted 2-azetidinones useful as hypocholesterolemic agents
EP1413331B1 (fr)	2001-01-26	2007-10-03	Schering Corporation	Combinaisons de l'activateur du récepteur du peroxisome (PPAR) fenofibrate avec l'inhibiteur d'absorption de stérol ezetimibe pour des indications vasculaires
US7071181B2 (en)	2001-01-26	2006-07-04	Schering Corporation	Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
MY138301A (en)	2001-01-26	2009-05-29	Schering Corp	The use of substituted azetidinone compounds for the treatment of sitosterolemia
ATE437637T1 (de)	2001-05-02	2009-08-15	Nitromed Inc	Nitrosiertes und nitrosyliertes nebivolol und seine metaboliten, zusammensetzungen und anwendungsverfahren
US7056906B2 (en)	2001-09-21	2006-06-06	Schering Corporation	Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women
US7053080B2 (en)	2001-09-21	2006-05-30	Schering Corporation	Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
AU2002336609B2 (en)	2001-09-21	2006-08-24	Merck Sharp & Dohme Corp.	Treatment of xanthoma with azetidinone derivatives as sterol absorption inhibitors
AU2003287250B9 (en) *	2002-10-30	2010-01-28	Ptc Therapeutics, Inc.	Identifying therapeutic compounds based on their physical-chemical properties
JP2006508188A (ja)	2002-11-06	2006-03-09	シェーリング　コーポレイション	脱髄の処置のためのコレステロール吸収インヒビター
WO2004081003A1 (fr)	2003-03-07	2004-09-23	Schering Corporation	Composes d'azetidinone substitues, leurs formulations et leur utilisation pour traiter l'hypercholesterolemie
US7235543B2 (en)	2003-03-07	2007-06-26	Schering Corporation	Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
MXPA05009502A (es)	2003-03-07	2005-10-18	Schering Corp	Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia.
ITTO20030140U1 (it) *	2003-09-16	2005-03-17	Interfila Srl	Matita cosmetica
US7470798B2 (en) *	2003-09-19	2008-12-30	Edison Pharmaceuticals, Inc.	7,8-bicycloalkyl-chroman derivatives
US7838552B2 (en)	2004-06-04	2010-11-23	Forest Laboratories Holdings Limited	Compositions comprising nebivolol
US7803838B2 (en)	2004-06-04	2010-09-28	Forest Laboratories Holdings Limited	Compositions comprising nebivolol
AU2005278782B2 (en)	2004-07-30	2011-04-21	Torrent Pharmaceuticals Limited	Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol
KR20080016527A (ko) *	2005-01-31	2008-02-21	밀란 래보러토리즈, 인크.	하이드록시화된 네비볼롤을 함유하는 약학적 조성물
ES2532912T3 (es)	2005-06-01	2015-04-01	Edison Pharmaceuticals, Inc.	Compuestos terapéuticos redox activos para el tratamiento de enfermedades mitocondriales y otras condiciones y modulación de biomarcadores energéticos
EA019675B1 (ru)	2006-02-22	2014-05-30	Эдисон Фармасьютикалз, Инк.	Редокс-активные терапевтические средства для лечения митохондриальных заболеваний и модуляции биомаркера коэнзима q
DK2220030T3 (en)	2007-11-06	2016-04-11	Edison Pharmaceuticals Inc	4- (P-QUINONYL) -2-HYDROXYBUTANAMIDDERIVATER TO TREAT mitochondrial
WO2009091777A1 (fr) *	2008-01-15	2009-07-23	Forest Laboratories Holdings Limited	Le nébivolol dans le traitement du dysfonctionnement sexuel
EP2262508B1 (fr)	2008-03-05	2018-10-03	BioElectron Technology Corporation	Dérivés de p-quinone 2-substituée pour le traitement de maladies de stress oxydatif
US8314153B2 (en)	2008-09-10	2012-11-20	Edison Pharmaceuticals, Inc.	Treatment of pervasive developmental disorders with redox-active therapeutics
EP2362726B1 (fr)	2008-10-14	2018-08-08	Bioelectron Technology Corporation	Traitement d'affections liées au stress oxydatif, notamment de la néphropathie aux produits de contraste, des radiolésions et des perturbations de la fonction des globules rouges
WO2010071800A1 (fr) *	2008-12-19	2010-06-24	Schering Corporation	Supplément alimentaire pour culture de cellules de mammifère et procédés d'utilisation
JP2012525399A (ja)	2009-04-28	2012-10-22	エジソンファーマシューティカルズ，インコーポレイテッド	トコトリエノールキノンを用いる、レーバー遺伝性視神経症および優性遺伝性視神経萎縮症の治療
US20130065910A1 (en) *	2010-06-04	2013-03-14	Comprehensive Drug Enterprises Ltd.	Oral meclizine aqueous formulations with taste flavoring agent
US9670170B2 (en)	2013-03-15	2017-06-06	Bioelectron Technology Corporation	Resorufin derivatives for treatment of oxidative stress disorders
US9296712B2 (en)	2013-03-15	2016-03-29	Edison Pharmaceuticals, Inc.	Resorufin derivatives for treatment of oxidative stress disorders
US9868711B2 (en)	2013-03-15	2018-01-16	Bioelectron Technology Corporation	Phenazine-3-one and phenothiazine-3-one derivatives for treatment of oxidative stress disorders
DE102014107132A1 (de)	2014-05-20	2015-11-26	Corden Pharma International Gmbh	Verfahren zur Herstellung von Epoxiden die in der Herstellung von Nebivolol und dessen Derivaten einsetzbar sind
CN107106523A (zh) *	2014-10-24	2017-08-29	朗齐生物医学股份有限公司	脱克钙药物在用于制备治疗癌症的医药组合物中的用途
CA2971252A1 (fr)	2014-12-16	2016-06-23	Bioelectron Technology Corporation	Formes polymorphes et amorphes de (r)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyle)butanamide
JP6905527B2 (ja)	2015-12-17	2021-07-21	ピーティーシーセラピューティクス，インコーポレイテッド	酸化ストレス障害を処置するためのフルオロアルキル、フルオロアルコキシ、フェノキシ、ヘテロアリールオキシ、アルコキシ、およびアミノ１，４−ベンゾキノン誘導体

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1337432C (fr) *	1988-03-23	1995-10-24	Raymond M. Xhonneux	Methode de reduction de la tension arterielle
TW355683B (en) *	1994-02-17	1999-04-11	Janssen Pharmaceutica Nv	Composition containing micronized nebivolol
AU700364B2 (en) *	1994-12-28	1999-01-07	Janssen Pharmaceutica N.V.	Use of nebivolol as an anti-atherogenic

1995
- 1995-12-21 AU AU43477/96A patent/AU700364B2/en not_active Expired
- 1995-12-21 JP JP8520223A patent/JPH10511655A/ja active Pending
- 1995-12-21 DE DE69526120T patent/DE69526120T2/de not_active Expired - Lifetime
- 1995-12-21 SI SI9530591T patent/SI0801564T1/xx unknown
- 1995-12-21 KR KR1019970703648A patent/KR100264348B1/ko not_active Expired - Lifetime
- 1995-12-21 DK DK95942209T patent/DK0801564T3/da active
- 1995-12-21 HU HU9800675A patent/HU226208B1/hu unknown
- 1995-12-21 EP EP95942209A patent/EP0801564B1/fr not_active Expired - Lifetime
- 1995-12-21 WO PCT/EP1995/005174 patent/WO1996019987A1/fr active IP Right Grant
- 1995-12-21 PT PT95942209T patent/PT801564E/pt unknown
- 1995-12-21 ES ES95942209T patent/ES2176354T3/es not_active Expired - Lifetime
- 1995-12-21 AT AT95942209T patent/ATE214924T1/de active
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- 1995-12-21 CA CA002207333A patent/CA2207333C/fr not_active Expired - Fee Related
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- 1995-12-21 SK SK856-97A patent/SK282144B6/sk not_active IP Right Cessation
- 1995-12-21 CZ CZ19971919A patent/CZ287513B6/cs not_active IP Right Cessation
- 1995-12-21 CN CNB951971492A patent/CN1167418C/zh not_active Expired - Lifetime
1997
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Also Published As

Publication number	Publication date
KR100264348B1 (ko)	2000-08-16
NO972980D0 (no)	1997-06-26
CZ287513B6 (en)	2000-12-13
DE69526120T2 (de)	2002-11-28
EP0801564B1 (fr)	2002-03-27
ES2176354T3 (es)	2002-12-01
NO972980L (no)	1997-06-26
FI118884B (fi)	2008-04-30
SI0801564T1 (en)	2002-08-31
EP0801564A1 (fr)	1997-10-22
AU700364B2 (en)	1999-01-07
JPH10511655A (ja)	1998-11-10
ATE214924T1 (de)	2002-04-15
SK85697A3 (en)	2000-04-10
CA2207333A1 (fr)	1996-07-04
CN1167418C (zh)	2004-09-22
SK282144B6 (sk)	2001-11-06
AU4347796A (en)	1996-07-19
CZ191997A3 (cs)	1999-01-13
MX9704669A (es)	1997-09-30
FI972793L (fi)	1997-06-27
CN1171739A (zh)	1998-01-28
PT801564E (pt)	2002-09-30
WO1996019987A1 (fr)	1996-07-04
US5874461A (en)	1999-02-23
HUT77927A (hu)	1998-11-30
CA2207333C (fr)	2006-10-17
DE69526120D1 (de)	2002-05-02
FI972793A0 (fi)	1997-06-27
DK0801564T3 (da)	2002-07-15
NZ298074A (en)	2001-01-26
HU226208B1 (en)	2008-06-30
US6075046A (en)	2000-06-13

Publication	Publication Date	Title
NO315687B1 (no)	2003-10-13	Anvendelse av nebivolol for fremstilling av et anti-aterogent middel
AU2001264680B2 (en)	2006-09-14	Cannabinoid drugs
EP1589964B1 (fr)	2011-11-23	Composes possedant des proprietes antiproliferatives
US20100234402A1 (en)	2010-09-16	Methods and compositions for treating spinal muscular atrophy
da Silva et al.	2022	Ellagic Acid prevents vascular dysfunction in small mesenteric arteries of ovariectomized hypertensive rats
JPH11501011A (ja)	1999-01-26	神経保護薬としての縮合ベンゾチアゾール類の利用
MXPA97004669A (en)	1998-07-03	Use of nebivolol as an antiaterogen
EP1199076A2 (fr)	2002-04-24	Médicament contenant du tocotriènol comme agent actif
US20060182828A1 (en)	2006-08-17	Methods of reducing lipid peroxidation and achieving related health benefits by the administration of tocopherol and sesame lignans
EP1303264A1 (fr)	2003-04-23	Compositions et procedes servant a traiter des maladies cardio-vasculaires
US20020115728A1 (en)	2002-08-22	Compositions and methods for treating cardiovascular disorders
WO2007116458A1 (fr)	2007-10-18	Agent thérapeutique pour maladie neurodégénérative
MXPA97006454A (en)	1998-07-03	Use of fused benzotiazoles comoneuroprotecto
Schmidt et al.	0	Types of Statins
AU2001272191A1 (en)	2002-01-21	Compositions and methods for treating cardiovascular disorders

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