Method for inhibiting C-jun expression using JAK-3 inhibitors

Abstract

The invention provides a method for inhibiting c-jun activation in mammalian or avian cells comprising contacting the cells with a substance that inhibits the activity of Janus family kinase 3 (JAK-3). The invention also provides a therapeutic method for preventing or treating a pathological condition in a mammal wherein c-jun activation is implicated and inhibition of its activation is desired comprising administering to a mammal in need of such therapy, an effective amount of a substance that inhibits the activity of JAK-3. Novel compounds that are JAK-3 inhibitors, as well as pharmaceutical compositions comprising the compounds are also provided.

What is claimed is:  
     
         1 . A method comprising inhibiting c-jun activation in mammalian or avian cells by contacting the cells with a substance that inhibits the activity of Janus family kinase 3 (JAK-3).  
     
     
         2 . The method of  claim 1  wherein the c-jun activation results from exposure of the cells to ara-C, a topoisomerase II inhibitor, ultraviolet radiation, an alkylating agent, or ionizing radiation.  
     
     
         3 . The method of  claim 1  wherein the c-jun activation results from exposure of the cells to ultraviolet radiation or ionizing radiation.  
     
     
         4 . The method of  claim 1  wherein the contacting is performed in vitro.  
     
     
         5 . The method of  claim 1  wherein the contacting is performed in vitro.  
     
     
         6 . The method of  claim 2  wherein the contacting occurs prior to the exposure.  
     
     
         7 . The method of  claim 2  wherein the contacting occurs after the exposure.  
     
     
         8 . The method of  claim 1  wherein the substance is a protein.  
     
     
         9 . The method of  claim 1  wherein the substance is a compound of formula I:  
       
         
           
           
               
               
           
         
       
       wherein 
 X is HN, R 11 N, S, O, CH 2 , or R 11 CH;  
 R 11  is hydrogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkanoyl;  
 R 1 -R 8  are each independently hydrogen, hydroxy, mercapto, amino, nitro, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylthio, or halo; wherein two adjacent groups of R 1 -R 5  together with the phenyl ring to which they are attached may optionally form a fused ring, for example forming a naphthyl or a tetrahydronaphthyl ring; and further wherein the ring formed by the two adjacent groups of R 1 -R 5  may optionally be substituted by 1, 2, 3, or 4 hydroxy, mercapto, amino, nitro, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylthio, or halo; and  
 R 9  and R 10  are each independently hydrogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo, or (C 1 -C 4 )alkanoyl; or R 9  and R 10  together are methylenedioxy; or a pharmaceutically acceptable salt thereof.  
 
     
     
         10 . The method of  claim 1  wherein the substance is 4-(4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline or 4-(3′-bromo-4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline; or a pharmaceutically acceptable salt thereof.  
     
     
         11 . The method of  claim 1  wherein the cells are mammalian.  
     
     
         12 . The method of  claim 1  wherein the cells are human.  
     
     
         13 . The method of  claim 1  wherein the cells are avian.  
     
     
         14 . A therapeutic method for preventing or treating a pathological condition in a mammal wherein c-jun activation is implicated and inhibition of its activation is desired comprising administering to a mammal in need of such therapy, an effective amount of a substance that inhibits the activity of JAK-3.