| abstract |
The present invention relates to 2-substituted 4-heteroaryl-pyrimidines,(Fig.I), wherein: X1 is CH and X2 is S; or one of X?1 and X2¿ is S, and the other of X?1 and X2¿ is N; Z is NH, NHCO, NHSO¿2?, NHCH2, CH2, CH2CH2, or CH=CH; R?1, R2 and R3¿ are independently H, alkyl, aryl, aralkyl, heterocycle, halogeno, NO¿2?, CN, OH, alkoxy, aryloxy, NH2, NH-R', N-(R')(R''), NH-COR', NH-aryl, N-(aryl)2, COOH, COO-R', COO-aryl, CONH2, CONH-R', CON-(R')(R''),CONH-aryl, CON-(aryl)2, SO3H, SO2NH2, CF3, CO-R', or CO-aryl, wherein alkyl, aryl, aralkyl, heterocycle and NH-aryl groups may be further substituted with one or more groups selected from halogeno, NO2, CN, OH, O-methyl, NH2, COOH, CONH2 and CF3; at least one of the groups R?1 and R2¿ being other than H when either X1 or X2 is S; R?4, R5, R6, R7 and R8¿ are independently from each other H, substituted or unsubstituted lower alkyl, halogeno, NO¿2?, CN, OH, substituted or unsubstituted alkoxy, NH2, NH-R', alkyl-aryl, alkyl-heteroaryl, NH(C=NH)NH2, N(R')3?+¿, N(R')(R''), COOH, COO-R', CONH¿2?, CONH-R', CON-(R')(R''), SO3H, SO2NH2, CF3 or (CH2)nO(CH2)m NR'R'', (CH2)nCO2(CH2)mOR''' wherein n is 0,1,2 or 3 and m is 1, 2 or 3; their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependant kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like. |