US 8,026,370 B2Granted

Carboxylic acid derivative containing thiazole ring and pharmaceutical use thereof

AssigneeMitsubishi Tanabe Pharma Corporation

InventorsTakashi Tozawa, Osamu Tsuruta, Hiroshi Kitajima, Yoshiyuki Aoki, Naoko Ando, Hiroki Tamakawa

Life of this patent

Estimating the term…

Abstract

According to the present invention, a compound represented by the following formula (I) having a superior PPARα agonist action and concurrently showing a hypolipidemic action can be provided, and further, a compound useful as a synthetic intermediate for the compound can be provided.

Claims25

Dependent claims

A carboxylic acid derivative containing a thiazole ring represented by formula (I):

wherein R1 and R2 are the same or different and each is a hydrogen atom or an alkyl group, or R1 and R2 are bonded to each other to form a cycloalkyl group;
R3 is a hydrogen atom or an alkyl group;
R4 is a hydrogen atom, an alkyl group or an aryl group;
n is an integer of 1 to 5;
Y is an oxygen atom, a sulfur atom, —NR5—, —CONR5—, —NR5CO— or —NHCONR5—, wherein R5 is a hydrogen atom, an alkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group or a heteroarylalkyl group;
and
Z is a cycloalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group or a heteroarylalkyl group,
wherein, in the aforementioned groups, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group and a heteroarylalkyl group each optionally have substituent, or a pharmaceutically acceptable salt thereof.

5 more elements

A carboxylic acid derivative containing a thiazole ring selected from the group consisting of:

(40) 2-[(4-{2-[(4′-cyanobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(60-2) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)benzoic acid,
(66) 2-methyl-2-[(4-{2-[4-(morpholin-4-ylcarbonyl)phenoxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid,
(73) 2-{[4-(2-{[4′-(acetylamino)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(74) 2-{[4-(2-{[4′-(dimethylamino)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(92-3) 2-{[4-(2-{[4′-fluoro-3-(methoxycarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(93-1) 4′-fluoro-4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)biphenyl-3-carboxylic acid,
(93-3) 2-{[4-(2-{[4′-fluoro-3-(morpholin-4-ylcarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(149) 2-{[4-(2-{4-[4-(4-fluorophenyl)piperazin-1-yl]phenoxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(150) 2-methyl-2-({4-[2-(4-{4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}phenoxy)ethyl]-1,3-thiazol-2-yl}thio)propionic acid,
(152-3) 2-methyl-2-{[4-({[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}methyl)-1,3-thiazol-2-yl]thio}propionic acid,
(153) 2-[(4-{[(4′-fluorobiphenyl-4-yl)methoxy]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(154) 2-[(4-{[(4′-chlorobiphenyl-4-yl)methoxy]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(155-4) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(156) 2-[(4-{2-[(4′-chlorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(157) 2-methyl-2-{[4-(2-{[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}ethyl)-1,3-thiazol-2-yl]thio}propionic acid,
(391) 2-[(4-{2-[[3-(4-chlorophenoxy)propyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(392) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[3-(4-methoxyphenoxy)propyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(397) 2-[(4-{2-[[2-(benzyloxy)ethyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(398) 2-[(4-{2-[[3-(benzyloxy)propyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(437-2) 4-{[(2-{2-[(2-tert-butyl-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethyl)(5-ethylpyrimidin-2-yl)amino]methyl}benzoic acid,
(437-4) 2-[(4-{2-[{4-[(ethylamino)carbonyl]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(438) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[4-(pyrrolidin-1-ylcarbonyl)benzyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(455-3) 2-methyl-2-({4-[({[4′-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acid,
(456) 2-{[4-({[(4′-fluorobiphenyl-4-yl)carbonyl]amino}methyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(457) 2-{[4-({[(4′-chlorobiphenyl-4-yl)carbonyl]amino}methyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(458-3) 2-methyl-2-{[4-(2-oxo-2-{[4′-(trifluoromethyl)biphenyl-4-yl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid,
(459) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(460) 2-[(4-{2-[(4′-chlorobiphenyl-4-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(495) 2-((4-(2-((2-(benzyloxy)ethyl)(phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(502) 2-((4-(2-((2-(benzyloxy)ethyl)(2,4-difluorophenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(504) 2-[(4-{2-[[4-(2-hydroxyethyl)phenyl] (3-phenylpropyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(510) 2-((4-(2-((2-(benzyloxy)ethyl)(3,4-dimethoxyphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(514) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(nonyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(515) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(isobutyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(516) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(isopentyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(517) (E)-2-((4-(2-(cinnamyl(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(518) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(519) 2-((4-(2-((furan-2-ylmethyl)(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(525) 2-((4-(2-(heptyl(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(526) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(2-naphthylmethyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(528) (E)-2-((4-(2-(but-2-enyl(3-isopropylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(529) 2-((4-(2-((2-(benzyloxy)ethyl)(3-isopropylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(534) (E)-2-((4-(2-((3-isopropylphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(547) 2-((4-(2-(biphenyl-3-yl(2-(benzyloxy)ethyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(551) (E)-2-((4-(2-(biphenyl-3-yl(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(556) 2-((4-(2-((2-(benzyloxy)ethyl)(1-naphthyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(567) (E)-2-methyl-2-((4-(2-((3-(5-nitrofuran-2-yl)propen-2-yl)(4-phenoxyphenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(574) 2-((4-(2-((2-(benzyloxy)ethyl)(2,4-dimethylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(586) (E)-2-((4-(2-((4-butoxyphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(594) 2-((4-(2-((2-(benzyloxy)ethyl)(2-methoxyphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(605) (E)-2-methyl-2-((4-(2-((3-(5-nitrofuran-2-yl)propen-2-yl)(3,4,5-trimethoxyphenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(613) 2-((4-(2-((2-(benzyloxy)ethyl)(2-fluorophenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(624) (E)-2-((4-(2-((4-butylphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(668) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(4-(diethylamino)phenyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(669) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(4-(pyrrolidin-1-yl)phenyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(672) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(methoxycarbonylmethyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(673) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(ethoxycarbonyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(674) 2-((4-(2-((biphenyl-4-ylmethyl)(4-oxo-4,5-dihydrothiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(682) 2-methyl-2-((4-(2-((4′-nitro-biphenyl-4-yl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(683) 2-methyl-2-((4-(2-((4-(methylthio)phenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(692) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(697) 2-((4-(2-(3,4-methylenedioxyphenylamino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(718) 2-methyl-2-((4-(2-(4-(methylthio)phenoxy)ethyl)thiazol-2-yl)thio) propionic acid,
(723) 2-((4-(2-((3-(methoxycarbonyl)napht-2-yl)oxy)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(730) 2-((4-(2-(4-(3-methoxy-3-oxopropionyl)phenoxy)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid, and
(733-2) 2-methyl-2-[(4-{2-[(4′-nitrobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid,
or a pharmaceutically acceptable salt thereof.

65 more elements

A carboxylic acid derivative containing a thiazole ring selected from the group consisting of:

(50-1) benzoic acid 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxyethyl)thio]-1,3-thiazol-4-yl}ethoxy)phenyl ester,
(60-1) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)benzoic acid methyl ester,
(92-1) 2-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)-5-iodobenzoic acid methyl ester,
(92-2) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)-4′-fluoro-biphenyl-3-carboxylic acid methyl ester,
(93-2) 2-{[4-(2-{[4′-fluoro-3-(morpholin-4-ylcarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester,
(152-2) 2-methyl-2-{[4-({[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}methyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester,
(155-3) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid ethyl ester,
(281-1) 2-[(4-{2-[(3-chloro-5-methoxycarbonylpyridin-2-yl)(heptyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(437-1) 4-{[(2-{2-[(2-tert-butyl-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethyl)(5-ethylpyrimidin-2-yl)amino]methyl}benzoic acid methyl ester,
(437-3) 2-[(4-{2-[{4-[(ethylamino)carbonyl]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(439-1) 2-[(4-{2-[{4-[(tert-butoxycarbonyl)amino]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(439-3) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[4-(propionylamino)benzyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester,
(455-2) 2-methyl-2-({4-[({[4′-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)methyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl ester,
(458-2) 2-methyl-2-{[4-(2-oxo-2-{[4′-(trifluoromethyl)biphenyl-4-yl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester, and
(733-1) 2-methyl-2-[(4-{2-[(4′-nitrobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid tert-butyl ester,
or a pharmaceutically acceptable salt thereof.

13 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/667,006Filed 4 Nov 2005
Priority: JP 2004-3213474 Nov 2004
Published: US 2008/0167307 A110 Jul 2008
Granted: 27 Sep 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 277/36
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,…:…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

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US 2008/0167307 A1Pre-grant publication · published 10 Jul 2008
US 8,026,370 B2This patent

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US 8,026,370 B2Granted

Carboxylic acid derivative containing thiazole ring and pharmaceutical use thereof

AssigneeMitsubishi Tanabe Pharma Corporation

InventorsTakashi Tozawa, Osamu Tsuruta, Hiroshi Kitajima, Yoshiyuki Aoki, Naoko Ando, Hiroki Tamakawa

Life of this patent

Estimating the term…

Abstract

Claims25

Dependent claims

A carboxylic acid derivative containing a thiazole ring represented by formula (I):

wherein R1 and R2 are the same or different and each is a hydrogen atom or an alkyl group, or R1 and R2 are bonded to each other to form a cycloalkyl group;
R3 is a hydrogen atom or an alkyl group;
R4 is a hydrogen atom, an alkyl group or an aryl group;
n is an integer of 1 to 5;
Y is an oxygen atom, a sulfur atom, —NR5—, —CONR5—, —NR5CO— or —NHCONR5—, wherein R5 is a hydrogen atom, an alkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group or a heteroarylalkyl group;
and
Z is a cycloalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group or a heteroarylalkyl group,
wherein, in the aforementioned groups, an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group, an arylalkenyl group, an aryloxyalkyl group, a heteroaryl group and a heteroarylalkyl group each optionally have substituent, or a pharmaceutically acceptable salt thereof.

5 more elements

A carboxylic acid derivative containing a thiazole ring selected from the group consisting of:

(40) 2-[(4-{2-[(4′-cyanobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(60-2) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)benzoic acid,
(66) 2-methyl-2-[(4-{2-[4-(morpholin-4-ylcarbonyl)phenoxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid,
(73) 2-{[4-(2-{[4′-(acetylamino)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(74) 2-{[4-(2-{[4′-(dimethylamino)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(92-3) 2-{[4-(2-{[4′-fluoro-3-(methoxycarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(93-1) 4′-fluoro-4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)biphenyl-3-carboxylic acid,
(93-3) 2-{[4-(2-{[4′-fluoro-3-(morpholin-4-ylcarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(149) 2-{[4-(2-{4-[4-(4-fluorophenyl)piperazin-1-yl]phenoxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(150) 2-methyl-2-({4-[2-(4-{4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}phenoxy)ethyl]-1,3-thiazol-2-yl}thio)propionic acid,
(152-3) 2-methyl-2-{[4-({[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}methyl)-1,3-thiazol-2-yl]thio}propionic acid,
(153) 2-[(4-{[(4′-fluorobiphenyl-4-yl)methoxy]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(154) 2-[(4-{[(4′-chlorobiphenyl-4-yl)methoxy]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(155-4) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(156) 2-[(4-{2-[(4′-chlorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(157) 2-methyl-2-{[4-(2-{[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}ethyl)-1,3-thiazol-2-yl]thio}propionic acid,
(391) 2-[(4-{2-[[3-(4-chlorophenoxy)propyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(392) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[3-(4-methoxyphenoxy)propyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(397) 2-[(4-{2-[[2-(benzyloxy)ethyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(398) 2-[(4-{2-[[3-(benzyloxy)propyl](5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(437-2) 4-{[(2-{2-[(2-tert-butyl-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethyl)(5-ethylpyrimidin-2-yl)amino]methyl}benzoic acid,
(437-4) 2-[(4-{2-[{4-[(ethylamino)carbonyl]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(438) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[4-(pyrrolidin-1-ylcarbonyl)benzyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(455-3) 2-methyl-2-({4-[({[4′-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acid,
(456) 2-{[4-({[(4′-fluorobiphenyl-4-yl)carbonyl]amino}methyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(457) 2-{[4-({[(4′-chlorobiphenyl-4-yl)carbonyl]amino}methyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid,
(458-3) 2-methyl-2-{[4-(2-oxo-2-{[4′-(trifluoromethyl)biphenyl-4-yl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid,
(459) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(460) 2-[(4-{2-[(4′-chlorobiphenyl-4-yl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(495) 2-((4-(2-((2-(benzyloxy)ethyl)(phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(502) 2-((4-(2-((2-(benzyloxy)ethyl)(2,4-difluorophenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(504) 2-[(4-{2-[[4-(2-hydroxyethyl)phenyl] (3-phenylpropyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid,
(510) 2-((4-(2-((2-(benzyloxy)ethyl)(3,4-dimethoxyphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(514) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(nonyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(515) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(isobutyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(516) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(isopentyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(517) (E)-2-((4-(2-(cinnamyl(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(518) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(519) 2-((4-(2-((furan-2-ylmethyl)(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(525) 2-((4-(2-(heptyl(4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(526) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)(2-naphthylmethyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(528) (E)-2-((4-(2-(but-2-enyl(3-isopropylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(529) 2-((4-(2-((2-(benzyloxy)ethyl)(3-isopropylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(534) (E)-2-((4-(2-((3-isopropylphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(547) 2-((4-(2-(biphenyl-3-yl(2-(benzyloxy)ethyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(551) (E)-2-((4-(2-(biphenyl-3-yl(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(556) 2-((4-(2-((2-(benzyloxy)ethyl)(1-naphthyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(567) (E)-2-methyl-2-((4-(2-((3-(5-nitrofuran-2-yl)propen-2-yl)(4-phenoxyphenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(574) 2-((4-(2-((2-(benzyloxy)ethyl)(2,4-dimethylphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(586) (E)-2-((4-(2-((4-butoxyphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(594) 2-((4-(2-((2-(benzyloxy)ethyl)(2-methoxyphenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(605) (E)-2-methyl-2-((4-(2-((3-(5-nitrofuran-2-yl)propen-2-yl)(3,4,5-trimethoxyphenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(613) 2-((4-(2-((2-(benzyloxy)ethyl)(2-fluorophenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(624) (E)-2-((4-(2-((4-butylphenyl)(3-(5-nitrofuran-2-yl)propen-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(668) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(4-(diethylamino)phenyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(669) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(4-(pyrrolidin-1-yl)phenyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(672) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(methoxycarbonylmethyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(673) 2-((4-(2-((biphenyl-4-ylmethyl)(4-(ethoxycarbonyl)thiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(674) 2-((4-(2-((biphenyl-4-ylmethyl)(4-oxo-4,5-dihydrothiazol-2-yl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(682) 2-methyl-2-((4-(2-((4′-nitro-biphenyl-4-yl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(683) 2-methyl-2-((4-(2-((4-(methylthio)phenyl)amino)ethyl)thiazol-2-yl)thio) propionic acid,
(692) 2-((4-(2-((4-(2-hydroxyethyl)phenyl)amino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(697) 2-((4-(2-(3,4-methylenedioxyphenylamino)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(718) 2-methyl-2-((4-(2-(4-(methylthio)phenoxy)ethyl)thiazol-2-yl)thio) propionic acid,
(723) 2-((4-(2-((3-(methoxycarbonyl)napht-2-yl)oxy)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid,
(730) 2-((4-(2-(4-(3-methoxy-3-oxopropionyl)phenoxy)ethyl)thiazol-2-yl)thio)-2-methylpropionic acid, and
(733-2) 2-methyl-2-[(4-{2-[(4′-nitrobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid,
or a pharmaceutically acceptable salt thereof.

65 more elements

A carboxylic acid derivative containing a thiazole ring selected from the group consisting of:

(50-1) benzoic acid 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxyethyl)thio]-1,3-thiazol-4-yl}ethoxy)phenyl ester,
(60-1) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)benzoic acid methyl ester,
(92-1) 2-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)-5-iodobenzoic acid methyl ester,
(92-2) 4-(2-{2-[(2-tert-butoxy-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethoxy)-4′-fluoro-biphenyl-3-carboxylic acid methyl ester,
(93-2) 2-{[4-(2-{[4′-fluoro-3-(morpholin-4-ylcarbonyl)biphenyl-4-yl]oxy}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester,
(152-2) 2-methyl-2-{[4-({[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}methyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester,
(155-3) 2-[(4-{2-[(4′-fluorobiphenyl-4-yl)methoxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid ethyl ester,
(281-1) 2-[(4-{2-[(3-chloro-5-methoxycarbonylpyridin-2-yl)(heptyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(437-1) 4-{[(2-{2-[(2-tert-butyl-1,1-dimethyl-2-oxoethyl)thio]-1,3-thiazol-4-yl}ethyl)(5-ethylpyrimidin-2-yl)amino]methyl}benzoic acid methyl ester,
(437-3) 2-[(4-{2-[{4-[(ethylamino)carbonyl]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(439-1) 2-[(4-{2-[{4-[(tert-butoxycarbonyl)amino]benzyl}(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester,
(439-3) 2-{[4-(2-{(5-ethylpyrimidin-2-yl)[4-(propionylamino)benzyl]amino}ethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester,
(455-2) 2-methyl-2-({4-[({[4′-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)methyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl ester,
(458-2) 2-methyl-2-{[4-(2-oxo-2-{[4′-(trifluoromethyl)biphenyl-4-yl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester, and
(733-1) 2-methyl-2-[(4-{2-[(4′-nitrobiphenyl-4-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid tert-butyl ester,
or a pharmaceutically acceptable salt thereof.

13 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/667,006Filed 4 Nov 2005
Priority: JP 2004-3213474 Nov 2004
Published: US 2008/0167307 A110 Jul 2008
Granted: 27 Sep 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 277/36
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,…:…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…