UA75980C2 - Substituted 4-pheny1-4-[1h-imidazol-2-yl] piperidine derivative for reducing ischaemic damages - Google Patents

Substituted 4-pheny1-4-[1h-imidazol-2-yl] piperidine derivative for reducing ischaemic damages Download PDF

Info

Publication number: UA75980C2
Authority: UA; Ukraine
Prior art keywords: group; compounds; forms; compound; heart
Prior art date: 2001-10-15

Application number

UA20040503666A

Other languages

English (en)

Ukrainian (uk)

Inventor

Paul Adriaan Jan Janssen

Joseph Elisabeth Leenaerts

Francisco Javi Fernandez-Gadea

Paul Joannes Ludovic Herijgers

Theo Frans Meert

Marcel J M Borgers

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.)

2001-10-15

Filing date

2002-10-10

Publication date

2006-06-15

2002-10-10 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2006-06-15 Publication of UA75980C2 publication Critical patent/UA75980C2/uk

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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

UA20040503666A 2001-10-15 2002-10-10 Substituted 4-pheny1-4-[1h-imidazol-2-yl] piperidine derivative for reducing ischaemic damages UA75980C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP01203927		2001-10-15
PCT/EP2002/011371 WO2003039440A2 (en)	2001-10-15	2002-10-10	Substituted 4-phenyl-4-(1h-imidazol-2-yl)-piperidine derivatives for reducing ischaemic damage

Publications (1)

Publication Number	Publication Date
UA75980C2 true UA75980C2 (en)	2006-06-15

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ID=8181081

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Application Number	Title	Priority Date	Filing Date
UA20040503666A UA75980C2 (en)	2001-10-15	2002-10-10	Substituted 4-pheny1-4-[1h-imidazol-2-yl] piperidine derivative for reducing ischaemic damages

Country Status (26)

Country	Link
US (1)	US7390822B2 (de)
EP (1)	EP1438049B1 (de)
JP (1)	JP4418676B2 (de)
KR (1)	KR100967599B1 (de)
CN (1)	CN1283252C (de)
AR (1)	AR036800A1 (de)
AT (1)	ATE345799T1 (de)
AU (1)	AU2002363369B2 (de)
BR (1)	BR0213325A (de)
CA (1)	CA2462374C (de)
CY (1)	CY1106335T1 (de)
DE (1)	DE60216310T2 (de)
EA (1)	EA007657B1 (de)
ES (1)	ES2276980T3 (de)
HR (1)	HRP20040325A2 (de)
HU (1)	HUP0402332A3 (de)
IL (1)	IL161347A0 (de)
MX (1)	MXPA04003480A (de)
MY (1)	MY139586A (de)
NO (1)	NO20041681L (de)
NZ (1)	NZ531733A (de)
PL (1)	PL370371A1 (de)
PT (1)	PT1438049E (de)
UA (1)	UA75980C2 (de)
WO (1)	WO2003039440A2 (de)
ZA (1)	ZA200402816B (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW200403058A (en) *	2002-04-19	2004-03-01	Bristol Myers Squibb Co	Heterocyclo inhibitors of potassium channel function
CL2004000754A1 (es) *	2003-04-11	2005-02-25	Janssen Pharmaceutica Nv	Uso de compuestos derivados de 4-fenil-4-(1h-imidazol-2-il)piperidina, como agonistas delta-opioides no peptidicos, para preparar un medicamento util en prevenir o tratar trastornos del sistema nervioso central.
WO2005005478A2 (en) *	2003-07-02	2005-01-20	Bayer Healthcare Ag	Diagnostics and therapeutics for diseases associated with g protein-coupled opioid receptor; delta 1 (oprd1)
WO2005015242A1 (en) *	2003-08-06	2005-02-17	Bayer Healthcare Ag	Diagnostics and therapeutics for diseases associated with g protein-coupled opioid receptor kappa 1 (opkr1)
TW200633990A (en) *	2004-11-18	2006-10-01	Takeda Pharmaceuticals Co	Amide compound
JP5450435B2 (ja) *	2007-11-30	2014-03-26	バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	ヘテロアリールで置換されたピペリジン類
DE102009014484A1 (de)	2009-03-23	2010-09-30	Bayer Schering Pharma Aktiengesellschaft	Substituierte Piperidine
DE102009022896A1 (de)	2009-05-27	2010-12-02	Bayer Schering Pharma Aktiengesellschaft	Substituierte Piperidine
DE102009022894A1 (de)	2009-05-27	2010-12-02	Bayer Schering Pharma Aktiengesellschaft	Substituierte Piperidine
DE102009056387B9 (de) *	2009-10-30	2020-05-07	Osram Opto Semiconductors Gmbh	Kantenemittierender Halbleiterlaser mit einem Phasenstrukturbereich zur Selektion lateraler Lasermoden
CN111417394B (zh)	2017-10-19	2023-11-07	帝人制药株式会社	苯并咪唑衍生物及其用途
CN113209294B (zh) *	2020-02-05	2023-06-13	复旦大学	Dor激动剂在制备对抗肾脏纤维化药物中的应用

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2213000A1 (en)	1995-03-06	1996-09-12	Interneuron Pharmaceuticals, Inc.	Reduction of infarct volume using citicoline
EP0956339B1 (de)	1996-08-23	2005-10-12	Ludwig Institute For Cancer Research	Rekombinanter vaskulärer endothelzellen wachstumsfaktor d (vegf-d)
NZ500530A (en)	1997-04-25	2001-12-21	Collateral Therapeutics	Truncated VEGF-B, VEGF-C, VEGF-3, PlGF, VRF-2, poxvirus ORF-1 and ORF-2 proteins
US6103722A (en)	1997-07-23	2000-08-15	The Medical College Of Wisconsin Research Foundation Inc.	Ischemic preconditioning
GB2332373A (en) *	1997-12-19	1999-06-23	Merck & Co Inc	Treatment of coronary and/or peripheral ischemia using an antithrombotic agent and an angiogenesis promoter
BR9916371A (pt) *	1998-12-19	2001-09-18	Janssen Pharmaceutica Nv	Composto de espiro anti-histamìnico
EP1038872A1 (de) *	1999-02-22	2000-09-27	Pfizer Products Inc.	4-Phenyl-4-heteroarylpiperdine Derivate als Opioid-Rezeptorligande
US6297256B1 (en) *	1999-06-15	2001-10-02	Neurogen Corporation	Aryl and heteroaryl substituted pyridino derivatives GABA brain receptor ligands
JP4417108B2 (ja) *	2001-10-15	2010-02-17	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	新規な置換された４−フェニル−４−［１ｈ−イミダゾール−２−イル］−ピペリジン誘導体および選択的非ペプチドデルタオピオイドアゴニストとしてのそれらの使用
FR2831166B1 (fr)	2001-10-18	2004-02-27	Sanofi Synthelabo	Aralkyl-tetrahydro-pyridines, leur preparation et compositions pharmaceutiques les contenant

2002
- 2002-10-10 CA CA2462374A patent/CA2462374C/en not_active Expired - Lifetime
- 2002-10-10 NZ NZ531733A patent/NZ531733A/en not_active IP Right Cessation
- 2002-10-10 WO PCT/EP2002/011371 patent/WO2003039440A2/en not_active Ceased
- 2002-10-10 EA EA200400547A patent/EA007657B1/ru not_active IP Right Cessation
- 2002-10-10 MX MXPA04003480A patent/MXPA04003480A/es active IP Right Grant
- 2002-10-10 DE DE60216310T patent/DE60216310T2/de not_active Expired - Lifetime
- 2002-10-10 KR KR1020047002380A patent/KR100967599B1/ko not_active Expired - Fee Related
- 2002-10-10 US US10/492,778 patent/US7390822B2/en not_active Expired - Fee Related
- 2002-10-10 AT AT02799040T patent/ATE345799T1/de active
- 2002-10-10 PT PT02799040T patent/PT1438049E/pt unknown
- 2002-10-10 BR BR0213325-3A patent/BR0213325A/pt not_active Application Discontinuation
- 2002-10-10 JP JP2003541732A patent/JP4418676B2/ja not_active Expired - Fee Related
- 2002-10-10 AU AU2002363369A patent/AU2002363369B2/en not_active Ceased
- 2002-10-10 PL PL02370371A patent/PL370371A1/xx not_active Application Discontinuation
- 2002-10-10 IL IL16134702A patent/IL161347A0/xx not_active IP Right Cessation
- 2002-10-10 HR HR20040325A patent/HRP20040325A2/hr not_active Application Discontinuation
- 2002-10-10 UA UA20040503666A patent/UA75980C2/uk unknown
- 2002-10-10 HU HU0402332A patent/HUP0402332A3/hu unknown
- 2002-10-10 CN CNB028202961A patent/CN1283252C/zh not_active Expired - Fee Related
- 2002-10-10 EP EP02799040A patent/EP1438049B1/de not_active Expired - Lifetime
- 2002-10-10 ES ES02799040T patent/ES2276980T3/es not_active Expired - Lifetime
- 2002-10-11 MY MYPI20023801A patent/MY139586A/en unknown
- 2002-10-11 AR ARP020103836A patent/AR036800A1/es unknown
2004
- 2004-04-13 ZA ZA2004/02816A patent/ZA200402816B/en unknown
- 2004-04-23 NO NO20041681A patent/NO20041681L/no not_active Application Discontinuation
2007
- 2007-02-22 CY CY20071100249T patent/CY1106335T1/el unknown

Also Published As

Publication number	Publication date
MXPA04003480A (es)	2004-07-30
HUP0402332A2 (hu)	2005-02-28
CA2462374C (en)	2011-01-18
PT1438049E (pt)	2007-02-28
JP2005507943A (ja)	2005-03-24
CN1568186A (zh)	2005-01-19
ES2276980T3 (es)	2007-07-01
EP1438049B1 (de)	2006-11-22
US7390822B2 (en)	2008-06-24
AU2002363369B2 (en)	2008-08-21
DE60216310D1 (de)	2007-01-04
US20050004170A1 (en)	2005-01-06
KR100967599B1 (ko)	2010-07-05
NO20041681L (no)	2004-04-23
WO2003039440A3 (en)	2003-12-18
HUP0402332A3 (en)	2009-07-28
HRP20040325A2 (en)	2005-04-30
EA200400547A1 (ru)	2004-10-28
DE60216310T2 (de)	2007-06-21
AR036800A1 (es)	2004-10-06
NZ531733A (en)	2006-04-28
KR20050035120A (ko)	2005-04-15
MY139586A (en)	2009-10-30
WO2003039440A2 (en)	2003-05-15
PL370371A1 (en)	2005-05-16
BR0213325A (pt)	2004-10-13
CY1106335T1 (el)	2011-10-12
EA007657B1 (ru)	2006-12-29
IL161347A0 (en)	2004-09-27
ATE345799T1 (de)	2006-12-15
JP4418676B2 (ja)	2010-02-17
CA2462374A1 (en)	2003-05-15
CN1283252C (zh)	2006-11-08
ZA200402816B (en)	2005-06-29
EP1438049A2 (de)	2004-07-21
HK1072562A1 (en)	2005-09-02

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