Protein kinase inhibitors

Abstract

Pyrimidine- and triazine-based chemical compounds that are useful, for example, as protein kinase inhibitors for treating cancer, neurological disorders, autoimmune disorders, and other diseases, and methods of using such compounds

1 . A method of treating a mammal in need of such treatment, comprising the step of administering a compound having the structure 
     
       
         
         
             
             
         
       
       wherein 
       R1 is alkyl, alkenyl, alkynyl, aryl, or heteroaryl, 
       R2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, 
       each R3 is, independently, hydrogen, optionally substituted alkyl, alkenyl, alkynyl, aryl, heteroaryl, or halo, 
       (C) is substituted alkyl, alkenyl, or aryl, 
       n=2-6; and 
       X is CH or N. 
     
   
   
       2 . The method of  claim 1 , wherein X is nitrogen. 
   
   
       3 . The method of  claim 2 , wherein the compound is selected from the group consisting of 
     (11,14)3,5N-{cyclopropyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{iso-propyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{n-propyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{pyrid-3-yl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{(3-ethoxyphenyl)-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{(3-ethoxycarbonylphenyl)-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{3-(3-{[methyl(1-methylpyrrolidin-3-yl)amino]carbonyl}phenyl)-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{3-(piperazin-1-ylcarbonyl)phenyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{3-[3-(dimethylamino)pyrrolidin-1-yl]carbonyl}phenyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-[(3-{[3-(dimethylamino)pyrrolidin-1-yl]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-{[3-({[2-(dimethylamino)ethyl]amino}carbonyl)phenyl]amino}-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-({3-[(3-hydroxyazetidin-1-yl)carbonyl]phenyl}amino)-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-[(3-{[(3-hydroxycyclobutyl)amino]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-[(3-{[[2-(dimethylamino)ethyl](methyl)amino]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{4-[(3-{[methyl(1-methylpiperidin-4-yl)amino]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{[(3-{[3-(diethylamino)pyrrolidin-1-yl]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{[(3-{[3-(diethylamino)azetidin-1-yl]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; 
     (11,14)3,5N-{{[3-(piperazin-1-ylcarbonyl)phenyl]amino}-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one; and 
     (11,14)3,5N-{4-[(3-{[[2-(diethylamino)ethyl](methyl)amino]carbonyl}phenyl)amino]-pyrazolo[1,5-a][1,3,5]triazin-4-yl-amino}-(2N,4N)-phenyl-1,5-diaza-cyclotetradeca-8-one. 
   
   
       4 . The method of  claim 2 , wherein the compound is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       5 . The method of  claim 1 , wherein X is carbon. 
   
   
       6 . The method of  claim 5 , wherein the compound is selected from the group consisting of