Derivatives of pyrimido [6,1-a] isoquinolin-4-one

Abstract

The present invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their application as inhibitors of phosphodiesterase (PDE) isoenzymes. More particularly the invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their use in medicine for example as bronchodilators with anti-inflammatory properties.

1 - 50 . (canceled) 
     
     
         51 . A composition comprising a compound of formula I: 
       
         
           
           
               
               
           
         
         wherein
 each of R 1  and R 2  independently represents a C 1-6  alkyl or C 2-7  acyl group; 
 R 5  represents a hydrogen atom or a C 1-3  alkyl, C 2-3  alkenyl or C 2-3  alkynyl group; 
 R 6  represents a hydrogen atom or a C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, amino, C 1-6  alkylamino, di(C 1-6 )alkylamino or C 2-7  acylamino group; 
 each of R 7  and R 8  independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 2-7  acyl, C 1-6  alkylthio, C 1-6  alkoxy, C 3-6  cycloalkyl; 
 R 9  represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6  alkyl, C 2-4  alkenyl, C 2-6  alkynyl, C 2-7  acyl, C 1-6  alkylthio, C 1-6  alkoxy or C 3-6  cycloalkyl group; X represents a group CR 3 R 4 , wherein each of R 3  and R 4  independently represents a hydrogen atom or a C 1-3  alkyl group; 
 each of R 10  and R 11  independently represents a hydrogen atom, a C 1-3  alkyl, C 3-6  cycloalkyl or phenyl group; 
 Y represents an oxygen atom or a group CHNO 2 , NCN, NH or NNO 2 ; n is an integer from 2 to 4; or a salt thereof; and 
 
         further comprising an active agent selected from the group consisting of a β 2 -adrenoceptor agonist and a glucocorticoid steroid, and a veterinarily or pharmaceutically acceptable carrier or diluent. 
       
     
     
         52 . The composition of  claim 51 , wherein
 each of R 1  and R 2  represents a C 1-6  alkyl;   R 1  and R 2  are the same as each other;   each of R 3  and R 4  represents a hydrogen atom;   R 5  represents a hydrogen atom;   R 6  represents a hydrogen atom;   each of R 7  and R 8  represents a O 1-6  alkyl;   R 7  and R 8  are the same as each other;   R 9  represents a halogen atom or a methyl or acetyl group;   Y represents an oxygen atom or a group CHNO 2 ; and n is 2.   
     
     
         53 . The composition of  claim 52 , wherein each of R 1  and R 2  represents a O 1-4  alkyl, group; and each of R 7  and R 8  represents a methyl, ethyl or isopropyl group. 
     
     
         54 . The composition of  claim 51 , wherein the composition is a pharmaceutical composition for human medicine. 
     
     
         55 . The composition of  claim 54 , adapted for administration by aerosol.