HUP0203521A2 - Kristályos 4-karboxi-amino-2-etil-1,2,3,4-tetrahidro-kinolin CEPT inhibitor, eljárás az előállítására, ezt tartalmazó gyógyszerkészítmény és alkalmazása - Google Patents

Kristályos 4-karboxi-amino-2-etil-1,2,3,4-tetrahidro-kinolin CEPT inhibitor, eljárás az előállítására, ezt tartalmazó gyógyszerkészítmény és alkalmazása Download PDF

Info

Publication number: HUP0203521A2
Authority: HU; Hungary
Prior art keywords: crystal; formula; trifluoromethyl; dihydro; carboxylic acid
Prior art date: 1999-11-30

Application number

HU0203521A

Other languages

English (en)

Hungarian (hu)

Inventor

Douglas John Meldrum Allen

Troy Anthony Appleton

Lyle Robinson Brostrom

Derek Lawrence Tickner

Original Assignee

Pfizer Products 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.)

1999-11-30

Filing date

2000-11-14

Publication date

2003-02-28

2000-11-14 Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.

2003-02-28 Publication of HUP0203521A2 publication Critical patent/HUP0203521A2/hu

Links

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- 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
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- 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
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Cardiology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Obesity (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Quinoline Compounds (AREA)
Cephalosporin Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

HU0203521A 1999-11-30 2000-11-14 Kristályos 4-karboxi-amino-2-etil-1,2,3,4-tetrahidro-kinolin CEPT inhibitor, eljárás az előállítására, ezt tartalmazó gyógyszerkészítmény és alkalmazása HUP0203521A2 (hu)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US16805199P	1999-11-30	1999-11-30
PCT/IB2000/001650 WO2001040190A1 (en)	1999-11-30	2000-11-14	4-carboxyamino-2-ethyl-1,2,3,4-tetrahydroquinoline crystal as cetp inhibitor

Publications (1)

Publication Number	Publication Date
HUP0203521A2 true HUP0203521A2 (hu)	2003-02-28

Family

ID=22609901

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU0203521A HUP0203521A2 (hu)	1999-11-30	2000-11-14	Kristályos 4-karboxi-amino-2-etil-1,2,3,4-tetrahidro-kinolin CEPT inhibitor, eljárás az előállítására, ezt tartalmazó gyógyszerkészítmény és alkalmazása

Country Status (28)

Country	Link
EP (1)	EP1246804A1 (et)
JP (1)	JP2003515592A (et)
KR (1)	KR20020058057A (et)
CN (1)	CN1402711A (et)
AP (1)	AP2002002531A0 (et)
AU (1)	AU1048801A (et)
BG (1)	BG106854A (et)
BR (1)	BR0015836A (et)
CA (1)	CA2392979A1 (et)
CO (1)	CO5271716A1 (et)
EA (1)	EA200200510A1 (et)
EC (1)	ECSP003792A (et)
EE (1)	EE200200277A (et)
GT (1)	GT200000199A (et)
HU (1)	HUP0203521A2 (et)
IL (1)	IL149097A0 (et)
IS (1)	IS6338A (et)
MA (1)	MA26845A1 (et)
MX (1)	MXPA02005354A (et)
NO (1)	NO20022558L (et)
OA (1)	OA12099A (et)
PA (1)	PA8506301A1 (et)
PE (1)	PE20010904A1 (et)
PL (1)	PL355892A1 (et)
TN (1)	TNSN00231A1 (et)
TR (1)	TR200201446T2 (et)
UY (1)	UY26454A1 (et)
WO (1)	WO2001040190A1 (et)

Families Citing this family (27)

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Publication number	Priority date	Publication date	Assignee	Title
US7115279B2 (en)	2000-08-03	2006-10-03	Curatolo William J	Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors
EE200400024A (et)	2001-06-21	2004-06-15	Pfizer Products Inc.	Kolesterüülestri ülekandevalgu inhibiitorite iseemulgeeruvad formulatsioonid
GT200200170A (es) *	2001-09-28	2003-05-23		Preparacion de inhibidor de cetp anhidro
RU2278659C9 (ru) *	2002-02-01	2007-02-20	Пфайзер Продактс Инк.	Способ получения гомогенных, высушенных распылением твердых аморфных дисперсий лекарственного средства с использованием модифицированной установки сушки распылением
EP1920766B1 (en) *	2002-02-01	2017-08-23	Bend Research, Inc	Pharmaceutical compositions of amorphous dispersions of drugs and lipophilic microphase-forming materials
EP1469832B2 (en)	2002-02-01	2016-10-26	Bend Research, Inc.	Pharmaceutical compositions of amorphous dispersions of drugs and lipophilic microphase-forming materials
EP1533292B1 (en)	2002-08-30	2007-02-14	Japan Tobacco Inc.	Dibenzylamine compound and medicinal use thereof
US7504508B2 (en)	2002-10-04	2009-03-17	Millennium Pharmaceuticals, Inc.	PGD2 receptor antagonists for the treatment of inflammatory diseases
US7211672B2 (en)	2002-10-04	2007-05-01	Millennium Pharmaceuticals, Inc.	PGD2 receptor antagonists for the treatment of inflammatory diseases
US20040132771A1 (en) *	2002-12-20	2004-07-08	Pfizer Inc	Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors
MXPA05005813A (es)	2002-12-20	2005-12-12	Pfizer Prod Inc	Formas de dosificacion que comprenden un inhibidor de la cetp y un inhibidor de la hmg-coa reductasa.
AU2004222436A1 (en)	2003-03-17	2004-09-30	Japan Tobacco Inc.	Method for increasing the oral bioavailability of S-(2-(((1- (2-ethylbutyl) cyclohexyl)carbonyl) amino) phenyl)-2-methylpropanethioate
HRP20050859A2 (en) *	2003-03-28	2006-02-28	Pfizer Products Inc.	1,2,4-suptituted 1,2,3,4-tetrahydro-and 1,2 dihydro-quinoline and 1,2,3,4-tetrahydro-quinoxaline derivatives as cetp inhibitors for the treatment of atherosclerosis and obesity
MXPA06001417A (es)	2003-08-04	2006-05-15	Pfizer Prod Inc	Composiciones farmaceuticas de adsorbatos de farmacos amorfos y materiales que forman microfases lipofilas.
CN1863778A (zh)	2003-10-08	2006-11-15	伊莱利利公司	用于治疗血脂异常的化合物及方法
AU2005233160B2 (en) *	2004-04-13	2011-06-02	Merck Sharp & Dohme Corp.	CETP inhibitors
EA200700119A1 (ru) *	2004-06-24	2007-10-26	Эли Лилли Энд Компани	Соединения и способы лечения дислипидемии
WO2006033001A1 (en) *	2004-09-23	2006-03-30	Pfizer Products Inc.	Quinoline compounds
US20070149567A1 (en) *	2004-09-23	2007-06-28	Pfizer Inc	Quinoline compounds
WO2006091674A1 (en)	2005-02-24	2006-08-31	Millennium Pharmaceuticals, Inc.	Pgd2 receptor antagonists for the treatment of inflammatory diseases
WO2006098394A1 (ja) *	2005-03-14	2006-09-21	Japan Tobacco Inc.	脂質吸収抑制方法および脂質吸収抑制剤
US7737155B2 (en)	2005-05-17	2010-06-15	Schering Corporation	Nitrogen-containing heterocyclic compounds and methods of use thereof
EP2134169A2 (en)	2007-03-09	2009-12-23	Indigene Pharmaceuticals Inc.	Combination of metformin r-(+) lipoate and antihyperlipidemic agents for the treatment of diabetic hyperglycemia and diabetic complications
US20110245209A1 (en)	2008-12-16	2011-10-06	Schering Corporation	Pyridopyrimidine derivatives and methods of use thereof
EP2379562A1 (en)	2008-12-16	2011-10-26	Schering Corporation	Bicyclic pyranone derivatives as nicotinic acid receptor agonists
TWI450896B (zh)	2009-06-30	2014-09-01	Lilly Co Eli	反式－４－〔〔（５ｓ）－５－〔〔〔３，５－雙（三氟甲基）苯基〕甲基〕（２－甲基－２ｈ－四唑－５－基）胺基〕－２，３，４，５－四氫－７，９－二甲基－１ｈ－１－苯并氮呯－１－基〕甲基〕－環己基羧酸
EP3174995B1 (en)	2014-07-30	2020-08-19	F.Hoffmann-La Roche Ag	Genetic markers for predicting responsiveness to therapy with hdl-raising or hdl mimicking agent

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5231102A (en) *	1989-03-08	1993-07-27	Merck Sharp & Dohme, Ltd.	Tetrahydroquinoline derivatives useful for neurodegenerative disorders
WO1998033775A1 (en) *	1997-02-03	1998-08-06	American Home Products Corporation	2-substituted-1-acyl-1,2-dihydroquinoline derivatives to increase hdl-cholesterol level
US6197786B1 (en) *	1998-09-17	2001-03-06	Pfizer Inc	4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines

2000
- 2000-11-09 CO CO00085285A patent/CO5271716A1/es unknown
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- 2000-11-14 TR TR2002/01446T patent/TR200201446T2/xx unknown
- 2000-11-14 AP APAP/P/2002/002531A patent/AP2002002531A0/en unknown
- 2000-11-14 KR KR1020027006914A patent/KR20020058057A/ko not_active Ceased
- 2000-11-14 EA EA200200510A patent/EA200200510A1/ru unknown
- 2000-11-14 PL PL00355892A patent/PL355892A1/xx not_active Application Discontinuation
- 2000-11-14 OA OA1200200158A patent/OA12099A/en unknown
- 2000-11-14 AU AU10488/01A patent/AU1048801A/en not_active Abandoned
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- 2000-11-14 IL IL14909700A patent/IL149097A0/xx unknown
- 2000-11-14 CA CA002392979A patent/CA2392979A1/en not_active Abandoned
- 2000-11-14 JP JP2001541875A patent/JP2003515592A/ja active Pending
- 2000-11-14 HU HU0203521A patent/HUP0203521A2/hu unknown
- 2000-11-14 EP EP00971662A patent/EP1246804A1/en not_active Withdrawn
- 2000-11-14 CN CN00816463A patent/CN1402711A/zh active Pending
- 2000-11-14 WO PCT/IB2000/001650 patent/WO2001040190A1/en not_active Ceased
- 2000-11-28 PE PE2000001267A patent/PE20010904A1/es not_active Application Discontinuation
- 2000-11-28 UY UY26454A patent/UY26454A1/es not_active Application Discontinuation
- 2000-11-29 GT GT200000199A patent/GT200000199A/es unknown
- 2000-11-29 TN TNTNSN00231A patent/TNSN00231A1/fr unknown
- 2000-11-29 EC EC2000003792A patent/ECSP003792A/es unknown
2002
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- 2002-05-27 MA MA26653A patent/MA26845A1/fr unknown
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Also Published As

Publication number	Publication date
OA12099A (en)	2006-05-04
AU1048801A (en)	2001-06-12
ECSP003792A (es)	2002-04-23
EP1246804A1 (en)	2002-10-09
EA200200510A1 (ru)	2002-10-31
MA26845A1 (fr)	2004-12-20
PA8506301A1 (es)	2002-08-26
CN1402711A (zh)	2003-03-12
UY26454A1 (es)	2001-07-31
IS6338A (is)	2002-04-12
CO5271716A1 (es)	2003-04-30
JP2003515592A (ja)	2003-05-07
EE200200277A (et)	2003-10-15
MXPA02005354A (es)	2002-12-11
CA2392979A1 (en)	2001-06-07
TNSN00231A1 (fr)	2002-05-30
PL355892A1 (en)	2004-05-31
BG106854A (bg)	2002-12-29
WO2001040190A1 (en)	2001-06-07
KR20020058057A (ko)	2002-07-12
TR200201446T2 (tr)	2002-11-21
IL149097A0 (en)	2002-11-10
AP2002002531A0 (en)	2002-06-30
NO20022558D0 (no)	2002-05-29
PE20010904A1 (es)	2001-09-10
NO20022558L (no)	2002-05-29
BR0015836A (pt)	2002-08-06
GT200000199A (es)	2002-05-23

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US4999358A (en)	1991-03-12	(1,2,3,4-tetrahydro-9-acridinimino)cyclohexane carboxylic acid and related compounds
MXPA00011855A (en)	2002-06-05	Method for making (-)-(2r,4s)-4- [(3,5-bis- trifluoromethyl-benzyl)- methoxycarbonylamino]- 2-ethyl-6- trifluoromethyl-3,4-dihydro- 2h-quinoline- 1-carboxylic acid ethyl ester
JP2808629B2 (ja)	1998-10-08	１，５―ベンゾチアゼピン―３―カルボン酸化合物
JP2025539352A (ja)	2025-12-05	オレキシン受容体２の置換大環状アミン調節因子
HK1038007B (en)	2005-04-08	Method for making 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinoline
JPH10503508A (ja)	1998-03-31	Ｉｉ型糖尿病の治療において有用なベンゾオキサゾールおよびピリジン誘導体
FR2463766A1 (fr)	1981-02-27	Nouvelles 1(2h)-isoquinolones, utiles notamment comme analgesiques