SK281908B6 - Heteroarylsubstituované deriváty 1,3-dioxolan-4-ylmetoxyfenyl-1- piperazinylfenyl-2,4-dihydro-2-alkyl-3h-1,2,4-triazol-3-ónu, spôsob a medziprodukty na ich výrobu a farmaceutické prostriedky - Google Patents

Heteroarylsubstituované deriváty 1,3-dioxolan-4-ylmetoxyfenyl-1- piperazinylfenyl-2,4-dihydro-2-alkyl-3h-1,2,4-triazol-3-ónu, spôsob a medziprodukty na ich výrobu a farmaceutické prostriedky Download PDF

Info

Publication number: SK281908B6
Authority: SK; Slovakia
Prior art keywords: alkyl; triazol; substituted; formula; dioxolan
Prior art date: 1994-10-27

Application number

SK507-97A

Other languages

English (en)

Slovak (sk)

Other versions

SK50797A3 (en

Inventor

Jan Heeres

Leo Jacobus Jozef Backx

Robert Jozef Maria Hendrickx

Der Eycken Luc Alfons Leo Van

Chaffoy De Courcelles Didier Robert Guy Gabriel De

Original Assignee

Janssen Pharmaceutica N. V.

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.)

1994-10-27

Filing date

1995-10-19

Publication date

2001-09-11

1995-05-31 Priority claimed from US08/455,304 external-priority patent/US5521186A/en

1995-10-19 Application filed by Janssen Pharmaceutica N. V. filed Critical Janssen Pharmaceutica N. V.

1998-04-08 Publication of SK50797A3 publication Critical patent/SK50797A3/sk

2001-09-11 Publication of SK281908B6 publication Critical patent/SK281908B6/sk

Links

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- C07D417/14—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 containing three or more hetero rings
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Steroid Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK507-97A 1994-10-27 1995-10-19 Heteroarylsubstituované deriváty 1,3-dioxolan-4-ylmetoxyfenyl-1- piperazinylfenyl-2,4-dihydro-2-alkyl-3h-1,2,4-triazol-3-ónu, spôsob a medziprodukty na ich výrobu a farmaceutické prostriedky SK281908B6 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP94203120		1994-10-27
US08/455,304 US5521186A (en)	1994-10-27	1995-05-31	Apolipoprotein-β synthesis inhibitors
PCT/EP1995/004111 WO1996013499A1 (en)	1994-10-27	1995-10-19	Apolipoprotein-b synthesis inhibitors

Publications (2)

Publication Number	Publication Date
SK50797A3 SK50797A3 (en)	1998-04-08
SK281908B6 true SK281908B6 (sk)	2001-09-11

Family

ID=26136684

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK507-97A SK281908B6 (sk)	1994-10-27	1995-10-19	Heteroarylsubstituované deriváty 1,3-dioxolan-4-ylmetoxyfenyl-1- piperazinylfenyl-2,4-dihydro-2-alkyl-3h-1,2,4-triazol-3-ónu, spôsob a medziprodukty na ich výrobu a farmaceutické prostriedky

Country Status (30)

Country	Link
US (1)	US5929075A (de)
EP (1)	EP0788496B1 (de)
JP (1)	JP3025907B2 (de)
KR (1)	KR100227231B1 (de)
CN (1)	CN1068000C (de)
AP (1)	AP779A (de)
AT (1)	ATE198889T1 (de)
AU (1)	AU697744C (de)
BG (1)	BG63694B1 (de)
BR (1)	BR9509436A (de)
CA (1)	CA2203274C (de)
CY (1)	CY2256B1 (de)
CZ (1)	CZ286476B6 (de)
DE (3)	DE122007000005I2 (de)
DK (1)	DK0788496T3 (de)
ES (1)	ES2155535T3 (de)
FI (1)	FI119548B (de)
GR (1)	GR3035519T3 (de)
HR (1)	HRP950532B1 (de)
HU (1)	HU219862B (de)
IL (1)	IL115771A (de)
LU (1)	LU91306I2 (de)
NO (1)	NO311937B1 (de)
NZ (1)	NZ295353A (de)
OA (1)	OA10479A (de)
PT (1)	PT788496E (de)
RO (1)	RO118715B1 (de)
SK (1)	SK281908B6 (de)
TR (1)	TR199501295A2 (de)
WO (1)	WO1996013499A1 (de)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69804994D1 (de) *	1997-11-03	2002-05-23	Janssen Pharmaceutica Nv	Arzneimittel enthaltend lipidsenkende verbindungen
HUP0102052A3 (en) *	1998-04-27	2002-10-28	Janssen Pharmaceutica Nv	Pellets having a core coated with a lipid lowering agent and a polymer and process for their preparation
WO2000037463A1 (en) *	1998-12-22	2000-06-29	Janssen Pharmaceutica N.V.	S-oxide lipid lowering compounds
DE19945982A1 (de)	1999-09-24	2001-03-29	Knoll Ag	Geschwindigkeitsbestimmte Partikel
US20050132022A1 (en) *	2003-12-12	2005-06-16	International Business Machines Corporation	Computer system with LAN-based I/O
JP4994043B2 (ja) *	2004-01-21	2012-08-08	エランコ・アニマル・ヘルス・アイルランド・リミテッド	ミトラタピデ経口用溶液
US7649002B2 (en)	2004-02-04	2010-01-19	Pfizer Inc	(3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
US7262318B2 (en) *	2004-03-10	2007-08-28	Pfizer, Inc.	Substituted heteroaryl- and phenylsulfamoyl compounds
EP1737460A2 (de) *	2004-04-09	2007-01-03	Janssen Pharmaceutica N.V.	Intermittierendes dosierschema zur behandlung von übergewicht mit mtp-hemmern
US20050288340A1 (en) *	2004-06-29	2005-12-29	Pfizer Inc	Substituted heteroaryl- and phenylsulfamoyl compounds
PA8660701A1 (es)	2005-02-04	2006-09-22	Pfizer Prod Inc	Agonistas de pyy y sus usos
WO2006129193A2 (en) *	2005-05-27	2006-12-07	Pfizer Products Inc.	Combination of a cannabinoid-1- receptor-antagonist and a microsomal triglyceride transfer protein inhibitor for treating obesity or mainataining weight loss
CA2617654A1 (en) *	2005-08-04	2007-02-08	Pfizer Limited	Piperidinoyl-pyrrolidine and piperidinoyl-piperidine compounds
US7741317B2 (en)	2005-10-21	2010-06-22	Bristol-Myers Squibb Company	LXR modulators
US7888376B2 (en)	2005-11-23	2011-02-15	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
AU2007219236B2 (en) *	2006-02-23	2012-06-21	Pfizer Limited	Melanocortin type 4 receptor agonist piperidinoylpyrrolidines
US8383660B2 (en)	2006-03-10	2013-02-26	Pfizer Inc.	Dibenzyl amine compounds and derivatives
CN101583593A (zh)	2006-11-13	2009-11-18	辉瑞产品公司	二芳基、二吡啶基和芳基-吡啶基衍生物及其用途
ATE547394T1 (de)	2006-12-01	2012-03-15	Bristol Myers Squibb Co	N-((3-benzyl)-2,2-(bis-phenyl)-propan-1- aminderivate als cetp-hemmer für die behandlung von atherosklerose und herz-kreislauf- erkrankungen
MX2009012739A (es)	2007-05-25	2009-12-10	Janssen Pharmaceutica Nv	Sintesis mejorada del metansulfonato(ester) de (2s-cis)-2-(bromometil)-2-(4-clorofenil)-1,3-dioxolan-4-metanol.
JP5530438B2 (ja) *	2008-08-06	2014-06-25	ファイザー・リミテッド	Ｍｃ４作動薬としてのジアゼピンおよびジアゾカン化合物
AU2011254654B2 (en) *	2010-05-19	2016-01-07	Sandoz Ag	Process for the preparation of chiral triazolones
CR20200464A (es)	2018-03-08	2021-04-14	Incyte Corp	Compuestos diólicos de aminopirazina como inhibidores de pi3k-y
WO2020010003A1 (en)	2018-07-02	2020-01-09	Incyte Corporation	AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4218458A (en) *	1978-06-23	1980-08-19	Janssen Pharmaceutica, N.V.	Heterocyclic derivatives of (4-aryloxy-methyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles
US4313953A (en) *	1978-06-23	1982-02-02	Janssen Pharmaceutica, N.V.	Heterocyclic derivatives of (4-aryloxymethyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles
US4766125A (en) *	1981-06-23	1988-08-23	Janssen Pharmaceutica N.V.	N-aryl-piperazinealkanamides useful for protecting hearts from myocardial injury caused by ischaemia, anoxia or hypoxia
US4619931A (en) *	1983-02-28	1986-10-28	Janssen Pharmaceutica, N.V.	[[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]methyl]-1H-imidazoles and 1H-1,2,4-triazoles
CA1292472C (en) *	1985-12-03	1991-11-26	Alfonsus Guilielmus Knaeps	Derivatives of ¬¬4-¬4-(4-phenyl-1-piperazinyl)- phenoxymethyl\|-1,3-dioxolan-2-yl\|methyl\|-1h-imidazoles and 1h-1,2,4-triazoles
NZ223799A (en) *	1987-03-25	1989-12-21	Janssen Pharmaceutica Nv	Azolylmethyl-dioxolanylmethoxyphenyl-piperazinyl-phenyl-triazolones and antimicrobial compositions
CA1331757C (en) *	1988-02-29	1994-08-30	Janssen Pharmaceutica Naamloze Vennootschap	5-lipoxygenase inhibiting 4-(4-phenyl-1-piperazinyl)phenols
AU6359594A (en) *	1993-03-04	1994-09-26	Cytoven International N.V.	Pharmaceutical tryptophan containing dipeptide compositions and methods of use thereof
US5521186A (en) *	1994-10-27	1996-05-28	Janssen Pharmaceutica N.V.	Apolipoprotein-β synthesis inhibitors

1995
- 1995-10-19 AU AU38680/95A patent/AU697744C/en not_active Ceased
- 1995-10-19 CA CA002203274A patent/CA2203274C/en not_active Expired - Fee Related
- 1995-10-19 DE DE122007000005C patent/DE122007000005I2/de active Active
- 1995-10-19 DE DE1995619995 patent/DE122007000005I1/de active Pending
- 1995-10-19 JP JP8514288A patent/JP3025907B2/ja not_active Expired - Fee Related
- 1995-10-19 RO RO97-00812A patent/RO118715B1/ro unknown
- 1995-10-19 PT PT95937804T patent/PT788496E/pt unknown
- 1995-10-19 NZ NZ295353A patent/NZ295353A/en not_active IP Right Cessation
- 1995-10-19 AT AT95937804T patent/ATE198889T1/de active
- 1995-10-19 US US08/817,247 patent/US5929075A/en not_active Expired - Lifetime
- 1995-10-19 SK SK507-97A patent/SK281908B6/sk not_active IP Right Cessation
- 1995-10-19 DK DK95937804T patent/DK0788496T3/da active
- 1995-10-19 CZ CZ19971198A patent/CZ286476B6/cs not_active IP Right Cessation
- 1995-10-19 AP APAP/P/1997/000968A patent/AP779A/en active
- 1995-10-19 WO PCT/EP1995/004111 patent/WO1996013499A1/en not_active Ceased
- 1995-10-19 BR BR9509436A patent/BR9509436A/pt not_active IP Right Cessation
- 1995-10-19 ES ES95937804T patent/ES2155535T3/es not_active Expired - Lifetime
- 1995-10-19 DE DE69519995T patent/DE69519995T2/de not_active Expired - Lifetime
- 1995-10-19 KR KR1019970702662A patent/KR100227231B1/ko not_active Expired - Fee Related
- 1995-10-19 EP EP95937804A patent/EP0788496B1/de not_active Expired - Lifetime
- 1995-10-19 HU HU9701956A patent/HU219862B/hu not_active IP Right Cessation
- 1995-10-19 CN CN95195885A patent/CN1068000C/zh not_active Expired - Fee Related
- 1995-10-20 TR TR95/01295A patent/TR199501295A2/xx unknown
- 1995-10-26 IL IL11577195A patent/IL115771A/xx not_active IP Right Cessation
- 1995-10-27 HR HR950532A patent/HRP950532B1/xx not_active IP Right Cessation
1997
- 1997-04-10 BG BG101402A patent/BG63694B1/bg unknown
- 1997-04-24 NO NO19971895A patent/NO311937B1/no not_active IP Right Cessation
- 1997-04-25 FI FI971784A patent/FI119548B/fi not_active IP Right Cessation
- 1997-04-25 OA OA60997A patent/OA10479A/en unknown
2001
- 2001-03-05 GR GR20010400359T patent/GR3035519T3/el unknown
2002
- 2002-01-04 CY CY0200004A patent/CY2256B1/xx unknown
2007
- 2007-01-17 LU LU91306C patent/LU91306I2/fr unknown

Also Published As

Publication number	Publication date
MX9703074A (es)	1997-07-31
IL115771A0 (en)	1996-01-19
OA10479A (en)	2002-04-09
DE122007000005I1 (de)	2007-04-26
CA2203274A1 (en)	1996-05-09
NO311937B1 (no)	2002-02-18
AU3868095A (en)	1996-05-23
CN1161695A (zh)	1997-10-08
FI971784L (fi)	1997-04-25
US5929075A (en)	1999-07-27
TR199501295A2 (tr)	1996-06-21
CN1068000C (zh)	2001-07-04
HUT77360A (hu)	1998-03-30
HRP950532B1 (en)	2001-06-30
AU697744B2 (en)	1998-10-15
BR9509436A (pt)	1998-01-06
FI971784A0 (fi)	1997-04-25
AU697744C (en)	2002-08-22
ES2155535T3 (es)	2001-05-16
CA2203274C (en)	2002-02-19
SK50797A3 (en)	1998-04-08
PT788496E (pt)	2001-07-31
NZ295353A (en)	1998-08-26
GR3035519T3 (en)	2001-06-29
NO971895L (no)	1997-04-24
NO971895D0 (no)	1997-04-24
JPH09511759A (ja)	1997-11-25
EP0788496A1 (de)	1997-08-13
RO118715B1 (ro)	2003-09-30
KR100227231B1 (ko)	1999-11-01
AP9700968A0 (en)	1997-04-30
BG63694B1 (bg)	2002-09-30
DE69519995D1 (en)	2001-03-01
FI119548B (fi)	2008-12-31
EP0788496B1 (de)	2001-01-24
CZ286476B6 (en)	2000-04-12
AP779A (en)	1999-11-03
HU219862B (hu)	2001-08-28
CZ119897A3 (cs)	1998-03-18
HRP950532A2 (en)	1997-08-31
BG101402A (en)	1997-10-31
LU91306I2 (fr)	2007-03-19
CY2256B1 (en)	2003-07-04
ATE198889T1 (de)	2001-02-15
JP3025907B2 (ja)	2000-03-27
WO1996013499A1 (en)	1996-05-09
DK0788496T3 (da)	2001-06-18
DE122007000005I2 (de)	2008-04-24
IL115771A (en)	2000-02-29
DE69519995T2 (de)	2001-08-23

Legal Events

Date

Code

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Description

2012-08-06

PC4A

Assignment and transfer of rights

Owner name: ELANCO ANIMAL HEALTH IRELAND LIMITED, DUBLIN, IE

Free format text: FORMER OWNER: JANSSEN PHARMACEUTICA N. V., BEERSE, BE

Effective date: 20110707

2012-08-06

SPCT

Transfer of rights of an spc

Owner name: ELANCO ANIMAL HEALTH IRELAND LIMITED, IE

Free format text: PRODUCT NAME: MITRATAPID; REGISTRATION NO/DATE: EU/2/06/063/001-003 20061124; FORMER OWNER: JANSSENPHARMACEUTICA N.V., BE

Spc suppl protection certif: 5994-2007 60

Filing date: 20070504

Extension date: 20201020

2013-07-02

MM4A

Patent lapsed due to non-payment of maintenance fees

Effective date: 20121019

Publication	Publication Date	Title
EP0788496B1 (de)	2001-01-24	Apolipoprotein-b syntheseinhibitoren
US5521186A (en)	1996-05-28	Apolipoprotein-β synthesis inhibitors
BG60865B1 (bg)	1996-05-31	Триазолови фунгицидни съединения и метод за получаването им
EP0871626B1 (de)	2001-11-07	Triazolone als apolipoprotein-b synthese ihibitoren
TW318848B (de)	1997-11-01
MXPA97003074A (en)	1997-12-01	Synthesis of apoliprotein synthesis
HK1012186B (en)	2002-02-22	Triazolones as apolipoprotein-b synthesis inhibitors