OA12781A - Thiazole and oxazole derivatives that modulate PPAR activity. - Google Patents

Thiazole and oxazole derivatives that modulate PPAR activity. Download PDF

Info

Publication number: OA12781A
Authority: OA; OAPI
Prior art keywords: methyl; phenyl; yloxy; thiazol; acetic acid
Prior art date: 2002-03-07

Application number

OA1200400233A

Other languages

English (en)

Inventor

Xue-Min Cheng

Noe Ouano Erasga

Gary Frderick Filzen

Andrew George Geyer

Chitase Lee

Bharatu Kalidas Trivedi

Original Assignee

Warner Lambert Co

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.)

2002-03-07

Filing date

2003-03-03

Publication date

2006-07-07

2003-03-03 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2006-07-07 Publication of OA12781A publication Critical patent/OA12781A/en

Links

230000000694 effects Effects 0.000 title abstract description 9
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 title abstract description 5
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 title abstract description 5
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title description 2
150000007978 oxazole derivatives Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 195
238000000034 method Methods 0.000 claims abstract description 22
208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 12
208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 11
241000124008 Mammalia Species 0.000 claims abstract description 9
-1 -(CH2)raNR6R7 Proteins 0.000 claims description 92
125000000217 alkyl group Chemical group 0.000 claims description 78
229910052739 hydrogen Inorganic materials 0.000 claims description 46
239000001257 hydrogen Substances 0.000 claims description 46
125000005842 heteroatom Chemical group 0.000 claims description 41
229910052760 oxygen Inorganic materials 0.000 claims description 40
125000003118 aryl group Chemical group 0.000 claims description 37
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
125000000304 alkynyl group Chemical group 0.000 claims description 32
229910052717 sulfur Inorganic materials 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 29
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
125000003342 alkenyl group Chemical group 0.000 claims description 25
125000004429 atom Chemical group 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 22
125000004432 carbon atom Chemical group C* 0.000 claims description 20
229910052736 halogen Inorganic materials 0.000 claims description 20
150000002367 halogens Chemical class 0.000 claims description 20
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
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125000001424 substituent group Chemical group 0.000 claims description 15
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125000006588 heterocycloalkylene group Chemical group 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
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VTGKVTQZAONBPL-UHFFFAOYSA-N 2-[8-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-4-oxochromen-5-yl]oxyacetic acid Chemical compound S1C(CSC=2C3=C(C(C=CO3)=O)C(OCC(O)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 VTGKVTQZAONBPL-UHFFFAOYSA-N 0.000 claims description 2
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DAAMIPJNRSFJBV-UHFFFAOYSA-N 2-[[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-6-oxo-7,8-dihydro-5h-naphthalen-1-yl]oxy]acetic acid Chemical compound S1C(CSC=2C=3CC(=O)CCC=3C(OCC(O)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 DAAMIPJNRSFJBV-UHFFFAOYSA-N 0.000 claims description 2
XJXJPQWJBAPENY-UHFFFAOYSA-N 2-[[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-7-oxo-6,8-dihydro-5h-naphthalen-1-yl]oxy]acetic acid Chemical compound S1C(CSC=2C=3CCC(=O)CC=3C(OCC(O)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 XJXJPQWJBAPENY-UHFFFAOYSA-N 0.000 claims description 2
IOCWGZNOOXOJDZ-UHFFFAOYSA-N 2-[[5-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-4-oxo-2,3-dihydrochromen-8-yl]oxy]acetic acid Chemical compound S1C(CSC=2C=3C(=O)CCOC=3C(OCC(O)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 IOCWGZNOOXOJDZ-UHFFFAOYSA-N 0.000 claims description 2
WSXPAZMHQPPIOW-UHFFFAOYSA-N 2-[[5-methyl-7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-2,3-dihydro-1h-inden-4-yl]oxy]acetic acid Chemical compound S1C(CSC=2C=3CCCC=3C(OCC(O)=O)=C(C)C=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 WSXPAZMHQPPIOW-UHFFFAOYSA-N 0.000 claims description 2
FJTRLFAKDFQDSC-UHFFFAOYSA-N 2-[[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-1-benzofuran-4-yl]oxy]acetic acid Chemical compound S1C(CSC=2C=3OC=CC=3C(OCC(O)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 FJTRLFAKDFQDSC-UHFFFAOYSA-N 0.000 claims description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms

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Chemical & Material Sciences (AREA)
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Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
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Animal Behavior & Ethology (AREA)
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Urology & Nephrology (AREA)
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Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic 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)
Thiazole And Isothizaole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
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OA1200400233A 2002-03-07 2003-03-03 Thiazole and oxazole derivatives that modulate PPAR activity. OA12781A (en)

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Application Number	Priority Date	Filing Date	Title
US36240002P	2002-03-07	2002-03-07

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OA12781A true OA12781A (en)	2006-07-07

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OA1200400233A OA12781A (en)	2002-03-07	2003-03-03	Thiazole and oxazole derivatives that modulate PPAR activity.

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US (1)	US6833380B2 (fr)
EP (1)	EP1485091A1 (fr)
JP (1)	JP2005524665A (fr)
KR (1)	KR20040091694A (fr)
CN (1)	CN1638768A (fr)
AP (1)	AP2004003123A0 (fr)
AR (1)	AR038883A1 (fr)
AU (1)	AU2003207891A1 (fr)
BR (1)	BR0308221A (fr)
CA (1)	CA2476580A1 (fr)
CO (1)	CO5601013A2 (fr)
EA (1)	EA200401160A1 (fr)
EC (1)	ECSP045275A (fr)
GT (1)	GT200300053A (fr)
HR (1)	HRP20040810A2 (fr)
IL (1)	IL163768A0 (fr)
IS (1)	IS7399A (fr)
MA (1)	MA27182A1 (fr)
MX (1)	MXPA04008624A (fr)
NO (1)	NO20044245L (fr)
OA (1)	OA12781A (fr)
PA (1)	PA8568701A1 (fr)
PE (1)	PE20031010A1 (fr)
PL (1)	PL372971A1 (fr)
TN (1)	TNSN04167A1 (fr)
TW (1)	TW200400027A (fr)
UY (1)	UY27704A1 (fr)
WO (1)	WO2003074052A1 (fr)
ZA (1)	ZA200406491B (fr)

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US6867224B2 (en) *	2002-03-07	2005-03-15	Warner-Lambert Company	Compounds that modulate PPAR activity and methods of preparation
US6875780B2 (en)	2002-04-05	2005-04-05	Warner-Lambert Company	Compounds that modulate PPAR activity and methods for their preparation
US20050203151A1 (en) *	2003-12-19	2005-09-15	Kalypsys, Inc.	Novel compounds, compositions and uses thereof for treatment of metabolic disorders and related conditions
EP1745014B1 (fr)	2004-05-05	2011-07-06	High Point Pharmaceuticals, LLC	Nouveaux composes, leur preparation et leur utilisation
US7968723B2 (en)	2004-05-05	2011-06-28	High Point Pharmaceuticals, Llc	Compounds, their preparation and use
EP1749000A4 (fr) *	2004-05-25	2009-12-30	Metabolex Inc	Triazoles substitués bicyliques comme modulateurs de ppar et méthodes de préparation
US7323480B2 (en) *	2004-05-25	2008-01-29	Metabolex, Inc.	Substituted triazoles as modulators of PPAR and methods of their preparation
AU2006265172B2 (en)	2005-06-30	2011-09-15	Vtv Therapeutics Llc	Phenoxy acetic acids as PPAR delta activators
CN1896069B (zh) *	2005-07-15	2011-10-05	中国科学院上海药物研究所	一类取代噻唑-4酮化合物、制备方法和用途
NZ568488A (en)	2005-12-22	2011-07-29	High Point Pharmaceuticals Llc	Phenoxy acetic acids as PPAR delta activators
CA2645719A1 (fr)	2006-03-09	2007-09-13	High Point Pharmaceuticals, Llc	Nouveaux composes, leur preparation et utilisation
AR059898A1 (es)	2006-03-15	2008-05-07	Janssen Pharmaceutica Nv	Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2
TW200900065A (en)	2007-03-07	2009-01-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
TW200845978A (en)	2007-03-07	2008-12-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
BRPI0817101A2 (pt)	2007-09-14	2017-05-09	Addex Pharmaceuticals Sa	4-(aril-x-fenil)-1h-piridin-2-onas 1,3-dissubstituídas
ES2409215T3 (es)	2007-09-14	2013-06-25	Janssen Pharmaceuticals, Inc.	4-fenil-1H-piridin-2-onas 1-3-disustituidas
SI2203439T1 (sl)	2007-09-14	2011-05-31	Ortho Mcneil Janssen Pharm	1',3'-disubstituirani 4-fenil-3,4,5,6-tetrahidro-2H-1'H-(1,4')bipiridinil-2'-oni
ES2637794T3 (es)	2007-11-14	2017-10-17	Janssen Pharmaceuticals, Inc.	Derivados de imidazo[1,2-A]piridina y su uso como moduladores alostéricos positivos de receptores MGLUR2
ES2439291T3 (es)	2008-09-02	2014-01-22	Janssen Pharmaceuticals, Inc.	Derivados de 3-azabiciclo[3.1.0]hexilo como moduladores de receptores de glutamato metabotrópicos
CA2738849C (fr)	2008-10-16	2016-06-28	Addex Pharma S.A.	Derives d'indole et de benzomorpholine en tant que modulateurs des recepteurs metabotropiques du glutamate
ES2401691T3 (es)	2008-11-28	2013-04-23	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	Derivados de indol y de benzoxacina como moduladores de los receptores metabotrópicos de glutamato
MY153913A (en)	2009-05-12	2015-04-15	Janssen Pharmaceuticals Inc	7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
ES2440001T3 (es)	2009-05-12	2014-01-27	Janssen Pharmaceuticals, Inc.	Derivados de 1,2,4-triazolo[4,3-A]piridina y su uso para el tratamiento o prevención de trastornos neurológicos y psiquiátricos
SG176018A1 (en)	2009-05-12	2011-12-29	Janssen Pharmaceuticals Inc	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
ES2552455T3 (es)	2010-11-08	2015-11-30	Janssen Pharmaceuticals, Inc.	Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2
CA2814998C (fr)	2010-11-08	2019-10-29	Janssen Pharmaceuticals, Inc.	Derives de 1,2,4-triazolo[4,3-a]pyridine et leur utilisation en tant que modulateurs allosteriques positifs des recepteurs mglur2
CN103298809B (zh)	2010-11-08	2016-08-31	杨森制药公司	1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途
JO3368B1 (ar)	2013-06-04	2019-03-13	Janssen Pharmaceutica Nv	مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar)	2013-09-06	2019-03-13	Janssen Pharmaceutica Nv	مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
ES2811087T3 (es)	2013-09-09	2021-03-10	Vtv Therapeutics Llc	Uso de agonistas de PPAR-delta para tratar la atrofia muscular
US10537573B2 (en)	2014-01-21	2020-01-21	Janssen Pharmaceutica Nv	Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use
IL279202B2 (en)	2014-01-21	2023-09-01	Janssen Pharmaceutica Nv	Combinations containing positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic subtype 2 receptor and their use
CN113045523B (zh) *	2019-12-27	2022-09-23	上海泓博智源医药股份有限公司	一种咪唑啉吡啶化合物中间体的制备方法
WO2023147309A1 (fr)	2022-01-25	2023-08-03	Reneo Pharmaceuticals, Inc.	Utilisation d'agonistes ppar-delta dans le traitement d'une maladie

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE236137T1 (de)	1996-02-02	2003-04-15	Merck & Co Inc	Heterocyclische verbindungen als antidiabetische mittel und für die behandlung von fettleibigkeit
WO1997028149A1 (fr)	1996-02-02	1997-08-07	Merck & Co., Inc.	Procede pour augmenter les niveaux de cholesterol hdl
EE03765B1 (et)	1996-08-19	2002-06-17	Japan Tobacco Inc.	Propioonhappe derivaadid ja nende kasutamine
GB9914977D0 (en)	1999-06-25	1999-08-25	Glaxo Group Ltd	Chemical compounds
AU7073400A (en)	1999-08-27	2001-03-26	Eli Lilly And Company	Biaryl-oxa(thia)zole derivatives and their use as ppars modulators
JP2004509084A (ja)	2000-08-23	2004-03-25	イーライ・リリー・アンド・カンパニー	オキサゾリル−アリールオキシ酢酸誘導体およびそのｐｐａｒアゴニストとしての使用
US6930120B2 (en)	2000-08-23	2005-08-16	Eli Lilly And Company	Oxazolyl-arylproplonic acid derivatives and their use as ppar agonists
GB0031109D0 (en)	2000-12-20	2001-01-31	Glaxo Group Ltd	Chemical compounds
JP2004517100A (ja)	2000-12-20	2004-06-10	グラクソ　グループ　リミテッド	ｈＰＰＡＲアルファアゴニストとしての置換オキサゾールおよびチアゾール
GB0031107D0 (en)	2000-12-20	2001-01-31	Glaxo Group Ltd	Chemical compounds
GB0111523D0 (en)	2001-05-11	2001-07-04	Glaxo Group Ltd	Chemical compounds
HUP0400023A2 (hu)	2001-05-29	2004-04-28	Kyoto Pharmaceutical Industries, Ltd.	Új heterociklusos származékok és gyógyászati alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények
PL367077A1 (en)	2001-06-07	2005-02-21	Eli Lilly And Company	Modulators of peroxisome proliferator activated receptors (ppar)
WO2002102780A1 (fr)	2001-06-18	2002-12-27	Ono Pharmaceutical Co., Ltd.	Compose derive de tetrahydroquinoline et medicament contenant ledit compose comme principe actif
AR036237A1 (es)	2001-07-27	2004-08-25	Bayer Corp	Derivados del acido indan acetico, intermediarios, y metodo para su preparacion, composicion farmaceutica y el uso de dichos derivados para la manufactura de un medicamento
US6869975B2 (en)	2001-09-14	2005-03-22	Tularik Inc.	Linked biaryl compounds
US20030207924A1 (en)	2002-03-07	2003-11-06	Xue-Min Cheng	Compounds that modulate PPAR activity and methods of preparation
US6867224B2 (en)	2002-03-07	2005-03-15	Warner-Lambert Company	Compounds that modulate PPAR activity and methods of preparation
US6875780B2 (en)	2002-04-05	2005-04-05	Warner-Lambert Company	Compounds that modulate PPAR activity and methods for their preparation

2002
- 2002-12-19 US US10/324,278 patent/US6833380B2/en not_active Expired - Fee Related
2003
- 2003-03-03 WO PCT/IB2003/000817 patent/WO2003074052A1/fr not_active Ceased
- 2003-03-03 EA EA200401160A patent/EA200401160A1/ru unknown
- 2003-03-03 AU AU2003207891A patent/AU2003207891A1/en not_active Abandoned
- 2003-03-03 MX MXPA04008624A patent/MXPA04008624A/es active IP Right Grant
- 2003-03-03 AP APAP/P/2004/003123A patent/AP2004003123A0/en unknown
- 2003-03-03 EP EP03704893A patent/EP1485091A1/fr not_active Withdrawn
- 2003-03-03 OA OA1200400233A patent/OA12781A/en unknown
- 2003-03-03 CA CA002476580A patent/CA2476580A1/fr not_active Abandoned
- 2003-03-03 JP JP2003572569A patent/JP2005524665A/ja not_active Withdrawn
- 2003-03-03 CN CNA038054639A patent/CN1638768A/zh active Pending
- 2003-03-03 KR KR10-2004-7013962A patent/KR20040091694A/ko not_active Ceased
- 2003-03-03 HR HRP20040810 patent/HRP20040810A2/hr not_active Application Discontinuation
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- 2003-03-03 PL PL03372971A patent/PL372971A1/xx not_active Application Discontinuation
- 2003-03-05 PE PE2003000214A patent/PE20031010A1/es not_active Application Discontinuation
- 2003-03-05 AR ARP030100739A patent/AR038883A1/es unknown
- 2003-03-06 TW TW092104847A patent/TW200400027A/zh unknown
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- 2003-03-07 UY UY27704A patent/UY27704A1/es not_active Application Discontinuation
- 2003-03-07 PA PA20038568701A patent/PA8568701A1/es unknown
2004
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- 2004-08-16 ZA ZA200406491A patent/ZA200406491B/en unknown
- 2004-08-24 CO CO04082303A patent/CO5601013A2/es not_active Application Discontinuation
- 2004-08-30 MA MA27840A patent/MA27182A1/fr unknown
- 2004-09-03 TN TNP2004000167A patent/TNSN04167A1/fr unknown
- 2004-09-24 EC EC2004005275A patent/ECSP045275A/es unknown
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Also Published As

Publication number	Publication date
HRP20040810A2 (en)	2004-12-31
MA27182A1 (fr)	2005-01-03
PA8568701A1 (es)	2003-11-12
NO20044245L (no)	2004-10-06
IS7399A (is)	2004-08-12
ZA200406491B (en)	2006-05-31
US6833380B2 (en)	2004-12-21
PL372971A1 (en)	2005-08-08
ECSP045275A (es)	2004-10-26
PE20031010A1 (es)	2003-12-12
JP2005524665A (ja)	2005-08-18
BR0308221A (pt)	2005-01-04
CA2476580A1 (fr)	2003-09-12
CN1638768A (zh)	2005-07-13
CO5601013A2 (es)	2006-01-31
EA200401160A1 (ru)	2005-02-24
WO2003074052A1 (fr)	2003-09-12
MXPA04008624A (es)	2004-12-06
TW200400027A (en)	2004-01-01
TNSN04167A1 (fr)	2007-03-12
US20030207916A1 (en)	2003-11-06
AP2004003123A0 (en)	2004-09-30
KR20040091694A (ko)	2004-10-28
GT200300053A (es)	2003-10-10
AU2003207891A1 (en)	2003-09-16
UY27704A1 (es)	2003-10-31
EP1485091A1 (fr)	2004-12-15
AR038883A1 (es)	2005-02-02
IL163768A0 (en)	2005-12-18

Publication	Publication Date	Title
OA12781A (en)	2006-07-07	Thiazole and oxazole derivatives that modulate PPAR activity.
US6867224B2 (en)	2005-03-15	Compounds that modulate PPAR activity and methods of preparation
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US20050203151A1 (en)	2005-09-15	Novel compounds, compositions and uses thereof for treatment of metabolic disorders and related conditions
AU2003001A (en)	2001-06-12	Substituted oxazoles and thiazoles derivatives as hppar alpha activators
HUP0201858A2 (en)	2002-09-28	Thiazole and oxazole derivatives and their pharmaceutical use
US20120283255A1 (en)	2012-11-08	Urea derivatives, methods for their manufacture, and uses therefor
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WO2007095603A2 (fr)	2007-08-23	Nouveaux inhibiteurs d'acétyl-coa carboxylase (acc) et leur utilisation dans le traitement du diabète, de l'obésité et du syndrome métabolique
WO2007085136A1 (fr)	2007-08-02	Dérivés de 1,3-benzodioxolecyclopentène, procédé de préparation et applications médicales
MXPA04007177A (es)	2004-10-29	Alimentacion para animales baja en fosforo y metodo para hacer la misma.
CA2633351C (fr)	2015-04-07	Derives cetone a heterocycles substitues en tant qu'inhibiteurs de l'histone desacetylase (hdac)
JP2009514973A (ja)	2009-04-09	Ｐｐａｒモジュレーターとしての化合物および組成物
WO2006117743A1 (fr)	2006-11-09	Composes aromatiques substitues, agents anti-diabetiques
JP3836521B2 (ja)	2006-10-25	２，４−チアゾリジンジオン誘導体、その製造法およびそれを含んでなる医薬組成物