European Journal of Medicinal Chemistry vol:44 issue:3 pages:1016-1023
A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC50 range from 6.67 mu M to 0.12 mu M. Among them, 6-(3,5-dimethylbenzy]) analogue 5q exhibited the most potent anti-HIV-1 activity (IC50 = 0.12 mu M, SI > 2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed. (C) 2008 Elsevier Masson SAS. All rights reserved.