5,6-trimethylenepyrimidin-4-one compounds

Abstract

Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA 2 and are of use in treating atherosclerosis.

12 .- 19 . (canceled) 
   
   
       20 . A method of treating Alzheimer's disease wherein the method comprises administering to a patient in need thereof an effective amount of a compound formula (I), neat, or admixed with a pharmaceutically acceptable carrier, wherein formula (I) is: 
     
       
         
         
             
             
         
       
     
     in which:
 R a  and R b  together with the pyrimidine ring carbon atoms to which they are attached form a fused 5-membered carbocyclic ring; 
 R 2 CH 2 X is 4-fluorobenzylthio; 
 R 3  is C (1-3) alkyl substituted by NR 8 R 9 ; or 
 R 3  is Het-C (0-2) alkyl in which Het is a 5- to 7-membered heterocyclyl ring comprising N and in which N is unsubstituted or substituted by C (1-6) alkyl; 
 R 4  and R 5  form a 4-(4-trifluoromethylphenyl)phenyl moiety; 
 R 8  and R 9 , which may be the same or different, are selected from the group consisting of hydrogen, or C (1-6) alkyl); and 
 X is S; 
 or a pharmaceutically acceptable salt thereof. 
 
   
   
       21 . The method of  claim 20  wherein the compound of formula (I) is:
 1-(N-(2-(diethylamino)ethyl)-N-(3-(4-trifluoromethylphenoxy)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one;   1-(N-(2-(diethylamino)ethyl)-N-(4-(4-trifluoromethylphenoxy)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one;   1-(N-(2-(diethylamino)ethyl)-N-(4-(4-trifluoromethylbiphenyl-4-yl)propyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one;   1-(N-(2-ethylamino-2-methylpropyl)-N-(4-(4-trifluoromethylphenyl)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one;   N-(2-tert-butylaminoethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)amino-carbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one;   1-(N-(2-(ethylamino)ethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one; or   1-(N-(1-(2-methoxyethyl)piperidin-4-yl)-N-(4-(4-trifluoromethylphenyl)benzyl)aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylene-pyrimidin-4-one;   or a pharmaceutically acceptable salt thereof.   
   
   
       22 . The method of  claim 20  wherein the compound of formula (I) is (848)1-(N-(2-(diethylamino)ethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one, or a pharmaceutically acceptable salt thereof. 
   
   
       23 . The method of  claim 20  wherein the compound of formula (I) is 1-(N-(2-(diethylamino)ethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one.