Quinazoline derivatives as medicaments

Abstract

The invention is directed to methods to inhibit TGF-β and/or p38-α kinase using compounds of the formula or the pharmaceutically acceptable salts thereof wherein R 3 is a noninterfering substituent; each Z is CR 2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R 2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

1 . A pharmaceutical composition for treating conditions characterized by enhanced p38-α activity and/or enhanced TGF-β activity which composition comprises 
 a therapeutically effective amount of a compound of the formula                          or the pharmaceutically acceptable salts thereof    wherein R 3  is a noninterfering substituent;    each Z is CR 2  or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N;    each R 2  is independently a noninterfering substituent;    L is a linker;    n is 0 or 1; and    Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents in admixture with at least one pharmaceutically acceptable excipient.    
   
   
       2 . The composition of  claim 1  which further contains an additional therapeutic agent.  
   
   
       3 . The composition of  claim 2  wherein said additional therapeutic agent is a corticosteroid, a monoclonal antibody, or an inhibitor of cell division.