Triazine compounds

Abstract

This invention relates to triazine compounds of formula (I): R 1 is aryl, or heteroaryl; each of R 2 , R 4 , and R 5 , independently, is R c , halogen, nitro, nitroso, cyano, azide, isothionitro, SR c , or OR c ; R 3 is R c , alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR c , OC(O)R c , SO 2 R c , S(O)R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d , NR c SO 2 , COR c , C(O)OR c , or C(O)NR c R d ; n is 0, 1, 2, 3, 4, 5, 6, or 7; X is O, S, S(O), S(O 2 ), or NR c ; Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), or S(O 2 ); Z is N; and W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ; in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, or alkylcarbonyl.

1 . A method for treating an interleukin-12 overproduction-related disorder, comprising administering to a subject in need thereof an effective amount of the compound of formula (I):  
     
       
         
         
             
             
         
       
       wherein  
       R 1  is  
       
         
           
           
               
               
           
         
       
       aryl, orheteroaryl;  
       each of R 2 , R 4 , and R 5 , independently, is R c , halogen, nitro, nitroso, cyano, azide, isothionitro, SR c , or OR c ;  
       R 3  is R c , alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR c , OC(O)R c , SO 2 R c , S(O 2 )R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR c , NR c C(O)NR c R d , NR c SO 2 R d , COR c , C(O)OR c , or C(O)NR c R d ;  
       n is 0, 1, 2, 3, 4, 5, 6, or 7;  
       X is O, S, S(O), S(O 2 ), or NR c ;  
       Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), S(O 2 ), or NR c ;  
       Z is N or CH; and  
       W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ;  
       in which each of R a  and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c  and R d , independently, is H, alkyl, or alkylcarbonyl; or a phamaceutically acceptable salt thereof.  
     
   
   
       2 . The method of  claim 1 , wherein R 1  is  
     
       
         
         
             
             
         
       
     
   
   
       3 . The method of  claim 2 , wherein W is O.  
   
   
       4 . The method of  claim 3 , wherein R 5  is H or alkyl.  
   
   
       5 . The method of  claim 2 , wherein X is NR c .  
   
   
       6 . The method of  claim 2 , wherein R c  is H, methyl, ethyl, or acetyl.  
   
   
       7 . The method of  claim 2 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.  
   
   
       8 . The method of  claim 7 , wherein R 3  is aryl or heteroaryl.  
   
   
       9 . The method of  claim 8 , wherein R 3  is pyridinyl.  
   
   
       10 . The method of  claim 7 , wherein R 3  is OR c , SR c , C(O)OR c , or C(O)NR c R d .  
   
   
       11 . The method of  claim 7 , wherein R 3  is  
     
       
         
         
             
             
         
       
       in which each of A and A′, independently, is O, S, or NH;  
       each of R e  and R f , independently is H, alkyl, aryl, or heteroaryl; and  
       m is 1 or 2.  
     
   
   
       12 . The method of  claim 2 , wherein one of R a  and R b  is  
     
       
         
         
             
             
         
       
       in which  
       B is NR i , O, or S;  
       B′ is N or CR i ;  
       R g  is H, alkyl, or alkoxyl;  
       R h  is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;  
       R i  is H, alkyl, or alkylcarbonyl;  
       p is 0, 1, or 2; and  
       q is 0, 1, 2, 3, or 4.  
     
   
   
       13 . The method of  claim 12 , wherein one of R a  and R b  is  
     
       
         
         
             
             
         
       
       the other of R a  and R b  is alkyl.  
     
   
   
       14 . The method of  claim 13 , wherein R g  is H, methyl, ethyl, methoxy, or ethoxy; Rh is F, Cl, CN, methoxy, methyl, or ethoxy; R i  is H, methyl, ethyl, or acetyl, and q is 0, 1, or 2.  
   
   
       15 . The method of  claim 14 , wherein R g  is methyl or methoxy; R i  is H; and q is 0.  
   
   
       16 . The method of  claim 14 , wherein W is O; and R 5  is H or alkyl.  
   
   
       17 . The method of  claim 16 , wherein X is NR c ; and R c  is H, methyl, ethyl, or acetyl.  
   
   
       18 . The method of  claim 14 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.  
   
   
       19 . The method of  claim 18 , wherein R 3  is aryl or heteroaryl.  
   
   
       20 . The method of  claim 19 , wherein R 3  is pyridinyl.  
   
   
       21 . The method of  claim 20 , wherein R 1  is  
     
       
         
         
             
             
         
       
       in which D is O, S, or NR m ;  
       D′ is N or CR m ;  
       R j  is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;  
       R k  is aryl or heteroaryl;  
       R l  is H, alkyl, or alkylcarbonyl;  
       R m  is H, alkyl, or alkylcarbonyl;  
       r is 0, 1, or 2;  
       s is 0 or 1;  
       t is 0, 1, 2, 3, or 4; and  
       u is 0, 1, 2, 3, 4, or 5.  
     
   
   
       22 . The method of  claim 14 , wherein R 3  is OR c , SR c , C(O)OR c  or C(O)NR c R d .  
   
   
       23 . The method of  claim 14 , wherein R 3  is  
     
       
         
         
             
             
         
       
       in which each of A and A′, independently, is O, S, or NH;  
       each of R e  and R f , independently is H, alkyl, aryl, or heteroaryl; and  
       m is 1 or 2.  
     
   
   
       24 . The method of  claim 1 , wherein Z is CH.  
   
   
       25 . The method of  claim 24 , wherein R 1  is