Spirocyclic CETP inhibitors

Patent metadata

Field	Value
Publication number	US-9717714-B2
Application number	US-201314653445-A
Country	US
Kind code	B2
Filing date	Dec 17, 2013
Priority date	Dec 19, 2012
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Merck Sharp & Dohme

Inventors

• Ondeyka Debra
• Qian Xiaoxia
• Vachal Petr
• Tyagarajan Sriram
• Smith Cameron J
• Li Hong
• Bao Jianming

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D263/52

  condensed with carbocyclic rings or ring systems · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title