Pyrrole-2,5-dithione derivatives as liver x receptor modulators
AssigneeAstraZeneca AB
InventorPatrik Holm
Life of this patent
Estimating the term…
Abstract
The present invention relates to certain novel compounds of the Formula I to processes for preparing such compounds, to their the utility in modulation of nuclear hormone receptors Liver X Receptor (LXR) α (NR1H3) and/or β (NR1H2) and in treating clinical conditions including cardiovascular diseases such as atherosclerosis; inflammatory diseases, Alzheimer's disease, lipid disorders (dyslipidemias) whether or not associated with insulin resistance, type 2 diabetes and other manifestations of the metabolic syndrome, to methods for their therapeutic use and to pharmaceutical compositions containing them.
Claims30
A compound of Formula I
- wherein:
- R1 is selected from phenyl(1-4C)alkyl wherein the phenyl is optionally substituted by (1-4C)alkoxycarbonyl or a group of formula NRaRb in which Ra and Rb independently represent H or (1-4C)alkyl;
- heteroaryl(1-4C)alkyl wherein the heteroaryl is optionally substituted by (1-4C)alkyl or a group of formula NRaRb in which Ra and Rb independently represent H or (1-4C)alkyl;
- or a (1-6C)alkyl group which is optionally substituted by one or more of the following:
- fluoro, (1-4C)alkoxycarbonyl, (1-3C)alkylthio or (1-3C)alkoxy optionally substituted by one or more fluoro;
- R2 is phenyl;
- R3 is selected from phenyl, indolyl or benzofuranyl each optionally substituted by one or more of the following:
- (1-3C)alkanoyl, (1-4C)alkoxy optionally substituted by one or more fluoro;
- (1-3C)alkylthio;
- or a group of formula NRaRb in which Ra and Rb independently represent H, (1-3C)alkyl or (1-3C)alkanoyl or Ra and Rb together with the nitrogen atom to which they are attached represent morpholino;
- X is O or S;
- or a pharmaceutically acceptable salt or solvate thereof, or a solvate of such a salt.
A compound selected from the following:
- 1-(2-Methoxyethyl)-4-[(4-methoxyphenyl)amino]-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-(2-Methoxyethyl)-3-[(4-methoxyphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dithione;
- 4-[(4-Methoxyphenyl)amino]-3-phenyl-1-(pyridin-3-ylmethyl)-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 3-[(4-Methoxyphenyl)amino]-4-phenyl-1-(pyridin-3-ylmethyl)-1H-pyrrole-2,5-dithione;
- 4-[(4-Methoxyphenyl)amino]-3-phenyl-1-(pyridin-4-ylmethyl)-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 3-[(4-Methoxyphenyl)amino]-4-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrrole-2,5-dithione;
- 1-Butyl-4-[(4-methoxyphenyl)amino]-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-Butyl-3-[(4-methoxyphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dithione;
- 4-[(4-Methoxyphenyl)amino]-3-phenyl-5-thioxo-1-(2,2,2-trifluoroethyl)-1,5-dihydro-2H-pyrrol-2-one;
- 3-[(4-Methoxyphenyl)amino]-4-phenyl-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2,5-dithione;
- 1-Benzyl-4-[(4-methoxyphenyl)amino]-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-Benzyl-3-[(4-methoxyphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dithione;
- 4-[(4-Methoxyphenyl)amino]-1-methyl-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 3-[(4-Methoxyphenyl)amino]-1-methyl-4-phenyl-1H-pyrrole-2,5-dithione;
- 1-Ethyl-4-[(4-methoxyphenyl)amino]-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-Ethyl-3-[(4-methoxyphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dithione;
- 1-[(6-Aminopyridin-3-yl)methyl]-4-{[4-(difluoromethoxy)phenyl]amino}-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-[(6-Aminopyridin-3-yl)methyl]-3-{[4-(difluoromethoxy)phenyl]amino}-4-phenyl-1H-pyrrole-2,5-dithione;
- 1-[(6-Aminopyridin-3-yl)methyl]-4-[(4-morpholin-4-ylphenyl)amino]-3-phenyl-5-thioxo-1,5-dihydro-2H-pyrrol-2-one;
- 1-[(6-Aminopyridin-3-yl)methyl]-3-[(4-morpholin-4-ylphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dithione;
- or a pharmaceutically acceptable salt or solvate thereof, or a solvate of such a salt.
15-27. (canceled)
(canceled)
Dependencies are inferred from the claim text.