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

Sanjay Babu Katiyar; Iti Bansal; J K Saxena; P M S Chauhan

doi:10.1016/j.bmcl.2004.10.046

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

Bioorg Med Chem Lett. 2005 Jan 3;15(1):47-50. doi: 10.1016/j.bmcl.2004.10.046.

Authors

Sanjay Babu Katiyar¹, Iti Bansal, J K Saxena, P M S Chauhan

Affiliation

¹ Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.

PMID: 15582408
DOI: 10.1016/j.bmcl.2004.10.046

Abstract

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 microg/mL concentration. Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10 microg/mL concentration and three compounds (13, 14 and 28) have shown 40-60% inhibition at 5 microg/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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Filaricides / chemical synthesis*
Filaricides / chemistry
Filaricides / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Setaria Nematode / drug effects*
Structure-Activity Relationship
Topoisomerase II Inhibitors*

Substances

Filaricides
Pyrimidines
Topoisomerase II Inhibitors