Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of antifilarial topoisomerase II inhibitors

A series of 21 compounds of trisubstituted pyrimidine derivatives have been synthesized and evaluated for their in vitro topoisomerase 11 inhibitory activity against filarial parasite Setaria cervi. Out of these, seven compounds (8, 11-14, 25 and 28) have shown 60-80% inhibition at 40 and 20 mug/mL concentration. Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10 mug/mL concentration and three compounds (13, 14 and 28) have shown 40-60% inhibition at 5 mug/mL concentration. All the above mentioned compounds have shown better topo 11 inhibitory activity than standard antifilarial drug (DEC) and enzyme topo 11 inhibitors (Novobiocin, Nalidixic acid). (C) 2004 Elsevier Ltd. All rights reserved.