Nitrogenous heterocyclic compounds

Abstract

The present invention relates to nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which have inhibitory activity on the phosphorylation of kinases, which inhibits the activity of such kinases. The invention is also related to a method of inhibiting kinases and treating disease states in a mammal by inhibiting the phosphorylation of kinases. In a particular aspect the present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of a PDGF receptor to hinder abnormal cell growth and cell wandering, and a method for preventing or treating cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis.

1 . A method of inhibiting phosphorylation of PDGF receptor in a patient comprising the step of administering a compound selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein  
         when the compound is of Formula I(a) or I(b), R 1  is a member selected from the group consisting of: CN, O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —O-butyl, —O-t-butyl, —O-isoamyl, 1-naphthyloxy, 2-naphthyloxy, 4-indolyloxy, 5-indolyloxy, 5-isoquinolyloxy, and position isomers and homologs thereof; and  
         when the compound is of Formula I(c), I(d), I(e), I(f), I(g) or I(h), R 1  is a member selected from the group consisting of: CN, —O—C 1-8 alkyl that is straight or branched chained, —O-phenyl, -naphthyloxy, -indolyloxy and -isoquinolinyloxy;  
         n is 1, 2 or 3;  
         R 3  is a member selected from the group consisting of:  
         —OH, —O—CH 3 , —O—CH 2 —CH 3 , —NH 2 , —N(—CH 3 ) 2 , —NH(—CH 2 -phenyl), —NH(-Phenyl), —CN  
         
           
             
             
                 
                 
             
           
         
         and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof to the patient.  
       
     
     
         2 . A method for inhibiting abnormal cell growth and cell wandering in a patient and thereby preventing or treating a cell-proliferative disease, comprising the step of administering a compound selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein  
         when the compound is of Formula I(a) or I(b), R 1  is a member selected from the group consisting of: CN, O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —O-butyl, —O-t-butyl, —O-isoamyl, 1-naphthyloxy, 2-naphthyloxy, 4-indolyloxy, 5-indolyloxy, 5-isoquinolyloxy, and position isomers and homo logs thereof; and  
         when the compound is of Formula I(c), I(d), I(e), I(f), I(g) or I(h), R 1  is a member selected from the group consisting of: CN, —O—C 1-8 alkyl that is straight or branched chained, —O-phenyl, -naphthyloxy, -indolyloxy and -isoquinolinyloxy;  
         n is 1, 2 or 3;  
         R 3  is a member selected from the group consisting of:  
         —OH, —O—CH 3 , —O—CH 2 —CH 3 , —NH 2 , —N(—CH 3 ) 2 , —NH(—CH 2 -phenyl), —NH(-phenyl), —CN  
         
           
             
             
                 
                 
             
           
         
         and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof to the patient.  
       
     
     
         3 . A method according to  claim 2 , wherein said cell-proliferative disease is selected from the group consisting of arteriosclerosis, vascular re-obstruction, restenosis, cancer and glomerulosclerosis.