Spirocyclic CETP inhibitors
View Patent ↗Compounds having the structure of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and may be useful for raising HDL-cholesterol and reducing LDL-cholesterol in human patients and for treating or preventing atherosclerosis. The chemical compounds that are disclosed cholesterol ester transfer protein (CETP) and are expected to have utility in raising HDL-C, lowering LDL-C, and in the treatment and prevention of atherosclerosis.
1. A compound having formula I, or a pharmaceutically acceptable salt thereof,
Wherein each R is H;
R 1 is unsubstituted cyclopropyl or cyclobutyl;
B is A 1 , wherein A 1 has the structure of formula II:
wherein Y 1 and Y 2 are each —CH— or —N—, with the proviso that Y 1 and Y 2 are not both —CH—;
R 1a is 3-fluoroazetidinyl, 4-morpholinyl, CF 3 , —N(CH 3 ) 2 , —N(CH 3 )(SO 2 CH 3 ), or CH 3 S—;
A is A 2 , wherein A 2 is 3,5-bis-trifluoromethylphenyl;
A 3 is
wherein Y 3 is —CH— or —N—;
X is 3-cyclobutyl-D 1 , 3-cyclobutyl-CH 2 OH, 2-methyl-4-phenyl-D 1 ,
2-methyl-4-phenyl-CH 2 OH, —CH 2 CH 2 D 1 , —CH 2 OH, or isopropyl, wherein D 1 is —CO 2 R 8 ;
R 8 is H or —CH 3 ;
R b is —OCH 3 or halogen;
d is 0; and
e is an integer from 0-3.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the structure below:
3. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.