Tricyclic compounds, preparation methods, and their uses

Abstract

The present invention relates to novel compounds that inhibit Lp-PLA 2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA 2 , for example atherosclerosis, Alzheimer's disease, and/or diabetic macular edema.

What is claimed is: 
     
         1 . A compound of Formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 Z is selected from the group consisting of C 1 -C 3 alkyl, —O—(C 1 -C 3 alkyl) and halo; 
 m is 0, 1, 2 or 3; 
 X is S, NH or —N—(C 1 -C 3 alkyl), 
 Y is—(CH 2 ) n —, wherein n is 0, 1, 2, or 3; 
 Ar is phenyl or heteroaryl, either of which is optionally substituted with one or more substituents selected from the group consisting of CN, halo, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 1 -C 3 haloalkyl; and 
 Ar′ is phenyl or heteroaryl, either of which is optionally substituted with one or more substituents selected from the group consisting of CN, halo, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 1 -C 3 haloalkyl. 
 
     
     
         2 . A compound of  claim 1 , wherein Z is —OCH 3 . 
     
     
         3 . A compound of  claim 1 , wherein Z is F or Cl. 
     
     
         4 . A compound of  claim 1 , wherein m is 0 or 1. 
     
     
         5 . A compound of  claim 1 , wherein X is S. 
     
     
         6 . A compound of  claim 1 , wherein Y is —CH 2 — or —CH 2 —CH 2 —. 
     
     
         7 . A compound of  claim 1 , wherein Ar is phenyl, which is optionally substituted with one or more substituents selected from the groups consisting of CN, CF 3  and halo. 
     
     
         8 . A compound of  claim 1 , wherein Ar is pyridinyl which is optionally substituted with one or more substituents selected from the groups consisting of CN and halo. 
     
     
         9 . A compound of  claim 1 , wherein Ar′ is phenyl, pyridinyl or pyrimidinyl, which is optionally substituted with one or more substituents selected from the group consisting of CH 3 , halo and CF 3 . 
     
     
         10 . A compound of Formula (I) according to  claim 1 , wherein the compound has a structure of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . A pharmaceutical composition comprising a compound of Formula (I) according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . A method for treating a neurodegeneration disease in a subject comprising administering to a subject in need thereof a safe and effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof according to  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the neurodegeneration disease is Alzheimer's disease. 
     
     
         14 . The method of  claim 12 , wherein the neurodegeneration disease is vascular dementia. 
     
     
         15 . The method of  claim 12 , wherein said subject is human.