US 8,008,302 B2Granted

N-hydroxyamide derivatives and use thereof

AssigneeMerck Serono SA

InventorsDominique Swinnen, Agnes Bombrun, Jerome Gonzalez, Stefano Crosignani, Patrick Gerber, Catherine Jorand-Lebrun

Life of this patent

Estimating the term…

Abstract

The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof, in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.

Claims24

Dependent claims

A N-hydroxyamide according to Formula (I),

wherein:
A is N;
R1 is selected from C1-C6 alkyl, C3-C8-cycloalkyl, aryl, pyridinyl, pyrazinyl, thiadiazolyl, pyrimidinyl, oxadiazolyl, quinolinyl, thienyl, benzofuranyl, amino and alkoxy;
R2 is selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8-cycloalkyl, and aryl;
R3 is selected from H, C1-C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl;
R4, R5, R6 and R7 are independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl;
or R4 and R7 form together a —CH2— linkage;
n is an integer selected from 1, 2, 3, 4, 5 and 6;
wherein R1-R7 may be substituted by from 1 to 5 substituents selected from the group consisting of C1-C6-alkyl, amino, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, and nitro;
Carbons (2) and (3) are two chiral centers, wherein chiral center (2) has a configuration selected from “S” and “R” and wherein chiral center (3) has a “S” configuration as well as pharmaceutically acceptable salts thereof.

7 more elements

A N-hydroxyamide compound selected from the group consisting of:

(2S,3S)-N,2-dihydroxy-5-methyl-3-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-pyrimidin-2-ylpiperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2S)-2-methyl-4-(4-methylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-3-{[(2R)-4-(2-fluoro-5-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-N,2-dihydroxy-3-{[4-(4-methoxyphenyl)piperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(4-chloro-2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-3-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-3-{[(1S,4S)-5-(4-fluorophenyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-N,2-dihydroxy-5-methyl-3-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]hexanamide;
(2R,3S)-N,2-dihydroxy-5-methyl-3-({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)hexanamide;
(2R,3S)-3-{[4-(2-fluorophenyl)piperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-N,2-dihydroxy-5-methyl-3-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}carbonyl)hexanamide;
(2S,3S)-3-{[(2R)-4-biphenyl-4-yl-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2S)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(3-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-N,2-dihydroxy-5-methyl-3-{[4-(5-phenyl-1,2,4-oxadiazol-3-yl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(5-phenylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanamide;
3-[(4-biphenyl-4-ylpiperazin-1-yl)carbonyl]-3,4-dideoxy-1-(hydroxyamino)-5-O-(phenylmethyl)-L-threo-pentose;
(2R,3S)-N,2-dihydroxy-5-methyl-3-{[4-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-3-{[4-(2-fluorophenyl)piperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-N,2-dihydroxy-5-methyl-3-({4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl}carbonyl)hexanamide;
(2R,3S)-3-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-3-{[4-(5-chloropyridin-2-yl)piperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2R,3S)-3-{[4-(5-bromopyridin-2-yl)piperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(4-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)hexanamide;
(2R,3S)-3-benzyl-N,2-dihydroxy-4-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}butanamide;
(2S,3S)-3-benzyl-N,2-dihydroxy-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanamide;
(2R,3S)-N,2-dihydroxy-3-methyl-4-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}butanamide;
(2S)-N,2-dihydroxy-3-methyl-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanamide;
(2S,3S)-3-{[(2R)-4-(4′-fluorobiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(4-ethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(3,4-dimethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(methylsulfonyl)phenyl]piperazin-1-yl}carbonyl)hexanamide;
(2S,3S)-N,2-dihydroxy-3-{[(2R)-4-(6-methoxy-2-naphthyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-3-({(2R)-4-[4-(1-benzofuran-3-yl)phenyl]-2-methylpiperazin-1-yl}carbonyl)-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-propoxyphenyl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)hexanamide;
(2S,3S)-3-{[(2R)-4-(4-tert-butylphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-propylphenyl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-3-(cyclopentylmethyl)-N,2-dihydroxy-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanamide;
(2S,3S)-3-{[(2R)-4-(2,3-dihydro-1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-3-{[(2R)-4-(4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-[((2R)-2-methyl-4-{4-[(trifluoromethyl)sulfonyl]phenyl}piperazin-1-yl)carbonyl]hexanamide;
(2S,3S)-N,2-dihydroxy-3-{[(2R)-4-(4′-methoxybiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(4-cyclohexylphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(2,2-difluoro-1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(3-fluoro-4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(3-fluoro-4-isopropoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-3-({(2R)-4-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpiperazin-1-yl}carbonyl)-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-quinolin-3-ylpiperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-methylphenyl)piperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-3-{[(2R)-4-(5-chloro-2-thienyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-3-{[(2R)-4-(3-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-3-{[(2R)-4-(4′-bromobiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}carbonyl)hexanamide;
(2S,3S)-3-{[(2R)-4-(4-tert-butoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-3-{[(2R)-4-(4-isopropoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-quinolin-6-ylpiperazin-1-yl]carbonyl}hexanamide;
(2S,3S)-3-({(2R)-4-[3,5-bis(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}carbonyl)-N,2-dihydroxy-5-methylhexanamide;
(2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(1,3-oxazol-5-yl)phenyl]piperazin-1-yl}carbonyl)hexanamide;
and
(2S,3S)-3-({(2R)-4-[4-(dimethylamino)phenyl]-2-methylpiperazin-1-yl}carbonyl)-N,2-dihydroxy-5-methylhexanamide.

69 more elements

A compound selected from the group consisting of:

(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(2-pyridinyl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-[(1S)-3-methyl-1-({(2R)-2-methyl-4-[4-(trifluoromethyl) pyridin-2-yl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-5-((1S)-4-(4-ethoxyphenyl)-1-{[(2R)-2-methyl-4-(2-pyridinyl) piperazinyl]carbonyl}butyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-4-(4-ethoxyphenyl)-1-{[(2S)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-4-(4-ethoxyphenyl)-1-{[(2R)-2-methyl-4-(2-pyrimidinyl)piperazinyl]carbonyl}butyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-4-(4-ethoxyphenyl)-1-{[(2R)-4-(2-fluorophenyl)-2-methyl piperazinyl]carbonyl}butyl)-2,2-dimethyl-1,3 -dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-pyrimidin-2-ylpiperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2S)-2-methyl-4-(4-methylpyridin-2-yl) piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-5-[(1S)-1-({(2R)-4-[2-fluoro-5-(methyloxy)phenyl]-2-methylpiperazin-1-yl}carbonyl)-3-methylbutyl]-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[4-(4-methoxyphenyl)piperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[2R)-4-(4-chloro-2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[(1S,4S)-5-(4-fluorophenyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-{(1S)-3-methyl-1-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]butyl}-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-[(1S)-3-methyl-1-({4-[4-(trifluoromethy)phenyl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[4-(2-fluorophenyl)piperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-{(1S)-3-methyl-1-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]butyl}-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-{(1S)-3-methyl-1-[((2R)-2-methyl-4-{4-[(trifluoromethyl)oxy]phenyl}piperazin-1-yl)carbonyl]butyl}-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-biphenyl-4-yl-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2S)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(3-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-(5-phenylpyridin-2-yl)piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
3-[(4-biphenyl-4-ylpiperazin-1-yl)carbonyl]-3,4-dideoxy-1,2-O-(1-methylethylidene)-5-O-(phenylmethyl)-L-threo-pentonic acid;
(5R)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl) piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[4-(2-fluorophenyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-[1S)-3-methyl-1-({4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5R)-5-(1-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methyl butyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[4-(5-chloropyridin-2-yl)piperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-{[4-(5-bromopyridin-2-yl)piperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1R)-1-{[(2R)-4-(4-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-[(1R)-3-methyl-1-({(2R)-2-methyl-4-[5-(trifluoromethyl) pyridin-2-yl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5R)-5-((1S)-1-benzyl-2-oxo-2-{4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}ethyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-benzyl-2-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-2-oxoethyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5R)-2,2-dimethyl-5-((1S)-1-methyl-2-oxo-2-{4- [4-(trifluoromethoxy)phenyl]piperazin-1-yl}ethyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-(1-methyl-2-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-2-oxoethyl)-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(4′-fluorobiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1R)-1-{[(2R)-4-(4-ethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(3,4-dimethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-[3-methyl-1-({(2R)-2-methyl-4-[4-(methylsulfonyl)phenyl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(6-methoxy-2-naphthyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-[(1S)-1-({(2R)-4-[4-(1-benzofuran-3-yl)phenyl]-2-methylpiperazin-1-yl}carbonyl)-3-methylbutyl]-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-(4-propoxyphenyl)piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-[(1S)-3-methyl-1-({(2R)-2-methyl-4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)butyl]-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(4-tert-butylphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-(4-propylphenyl)piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-(cyclopentylmethyl)-2-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-2-oxoethyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(2,3-dihydro-1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-{(1S)-3-methyl-1-[((2R)-2-methyl-4-{4-[(trifluoromethyl)sulfonyl]phenyl}piperazin-1-yl)carbonyl]butyl}-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(4′-methoxybiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-(1-{[(2R)-4-(4-cyclohexylphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(2,2-difluoro-1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-(1-{[(2R)-4-(3-fluoro-4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(3-fluoro-4-isopropoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-[(1S)-1-({(2R)-4-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpiperazin-1-yl}carbonyl)-3-methylbutyl]-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-quinolin-3-ylpiperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[(2R)-2-methyl-4-(4-methylphenyl)piperazin-1-yl]carbonyl}butyl)-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(5-chloro-2-thienyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one;
(5S)-5-((1S)-1-{[(2R)-4-(3-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one.

65 more elements

A compound selected from the group consisting of:

(2S,3S)-2-hydroxy-5-methyl-3-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-pyrimidin-2-ylpiperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2S)-2-methyl-4-(4-methylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-3-{[(2R)-4-(2-fluoro-5-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-2-hydroxy-3-{[4-(4-methoxyphenyl)piperazin-1-yl]carbonyl}-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(4-chloro-2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-3-{[4-(4-fluorophenyl)piperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-2-hydroxy-5-methyl-3-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]hexanoic acid;
(2R,3S)-2-hydroxy-5-methyl-3-({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)hexanoic acid;
(2R,3S)-3-{[4-(2-fluorophenyl)piperazin 1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-2-hydroxy-5-methyl-3-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}carbonyl)hexanoic acid;
(2S,3S)-3-{[(2R)-4-biphenyl-4-yl-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2S)-4-(2-fluorophenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(3-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-2-hydroxy-5-methyl-3-{[4-(5-phenyl-1,2,4-oxadiazol-3-yl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-(5-phenylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanoic acid;
5-O-benzyl-3-[(4-biphenyl-4-ylpiperazin-1-yl)carbonyl]-3,4-dideoxy-L-threo-pentonic acid;
(2R,3S)-2-hydroxy-5-methyl-3-{[4-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-3-{[4-(2-fluorophenyl)piperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-2-hydroxy-5-methyl-3-({4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]piperazin-1-ylcarbonyl)hexanoic acid;
(2R,3S)-3-{[(2R)-4-(5-chloropyridin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-3-{[4-(5-chloropyridin-2-yl)piperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2R,3S)-3-{[4-(5-bromopyridin-2-yl)piperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(4-chlorophenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-({(2R)-2-methyl-4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)hexanoic acid;
(2R,3S)-3-benzyl-2-hydroxy-4-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}butanoic acid;
(2S,3S)-3-benzyl-2-hydroxy-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanoic acid;
(2R,3S)-2-hydroxy-3-methyl-4-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}butanoic acid;
(2S)-2-hydroxy-3-methyl-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanoic acid;
(2S,3S)-3-{[(2R)-4-(4′-fluorobiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(4-ethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(3,4-dimethoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(methylsulfonyl)phenyl]piperazin-1-yl}carbonyl)hexanoic acid;
(2S,3S)-2-hydroxy-3-{[(2R)-4-(6-methoxy-2-naphthyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanoic acid;
(2S,3S)-3-({(2R)-4-[4-(1-benzofuran-3-yl)phenyl]-2-methylpiperazin-1-yl}carbonyl)-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-propoxyphenyl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)hexanoic acid;
(2S,3S)-3-{[(2R)-4-(4-tert-butylphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-propylphenyl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-3-(cyclopentylmethyl)-2-hydroxy-4-{(2R)-2-methyl-4-[4-(trifluoromethoxy)phenyl]piperazin-1-yl}-4-oxobutanoic acid;
(2S,3S)-3-{[(2R)-4-(2,3-dihydro-1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-3-{[(2R)-4-(4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-[((2R)-2-methyl-4-{4-[(trifluoromethyl)sulfonyl]phenyl}piperazin-1-yl)carbonyl]hexanoic acid;
(2S,3S)-2-hydroxy-3-{[(2R)-4-(4′-methoxybiphenyl-4-yl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(4-cyclohexylphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(1-benzofuran-5-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(2,2-difluoro-1,3-benzodioxol-5-yl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(3-fluoro-4-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-{[(2R)-4-(3-fluoro-4-isopropoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-3-({(2R)-4-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methylpiperazin-1-yl}carbonyl)-2-hydroxy-5-methyl hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-quinolin-3-ylpiperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-2-hydroxy-5-methyl-3-{[(2R)-2-methyl-4-(4-methylphenyl)piperazin-1-yl]carbonyl}hexanoic acid;
(2S,3S)-3-{[(2R)-4-(5-chloro-2-thienyl)-2-methylpiperazin-1-yl]carbonyl}-2-hydroxy-5-methylhexanoic acid;
(2S,3S)-2-hydroxy-3-{[(2R)-4-(3-methoxyphenyl)-2-methylpiperazin-1-yl]carbonyl}-5-methylhexanoic acid.

60 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/572,761Filed 25 Jul 2005 · us provisional application
Priority: EP 0410357426 Jul 2004
Published: US 2008/0021028 A124 Jan 2008
Granted: 30 Aug 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 211/46
Attached in position 4: having a hydrogen atom as the second substituent in position 4
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes

Family

Application60/591,111Us provisional application · filed 26 Jul 2004
Application60/648,924Us provisional application · filed 1 Feb 2005
US 2008/0021028 A1Pre-grant publication · published 24 Jan 2008
US 8,008,302 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

11/572,761Filed 25 Jul 2005 · us provisional application

Priority

EP 0410357426 Jul 2004

Published

US 2008/0021028 A124 Jan 2008

Granted

30 Aug 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 211/46
Attached in position 4: having a hydrogen atom as the second substituent in position 4
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes