Synthesis and biological evaluation of novel 6-substituted 5-alkyl-2-(arylcarbonylmethylthio)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

Abstract

A novel series of 2-arylcarbonylmethylthio-6-arylmethylpyrimidin-4(3H)-ones have been synthesized and evaluated for in vitro anti-HIV activities in MT-4 cells. Most of these new compounds showed moderate to potent activities against wild-type HIV-1 with an EC50 range from 8.97 μM to 0.010 μM. Among them, the 6-(3,5-dimethylbenzyl) analogue 5p was identified as the most promising compound (EC50 = 0.010 μM, SI > 31,800) associated with moderate activity against the HIV-1 double mutant RT strain K103N + Y181C. The structure-activity relationships of these new congeners were further discussed. © 2008 Elsevier Ltd. All rights reserved.