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

• Published in: Bioorganic & medicinal chemistry letters 2005-01, Vol.15 (1), p.47-50
• Main Authors: Katiyar, Sanjay Babu, Bansal, Iti, Saxena, J.K., Chauhan, P.M.S.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifilarial; Antiparasitic agents; Biological and medical sciences; Filaricides - chemical synthesis; Filaricides - chemistry; Filaricides - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pyrimidine; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Setaria Nematode - drug effects; Structure-Activity Relationship; Topoisomerase II; Topoisomerase II Inhibitors
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.10.046

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