| Abstract
| - Novel compounds related to2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3-methylbenzyl)-4-oxopyrimidine (3c, MC 639) have been synthesized and testedas inhibitors of humanimmunodeficiency virus type-1 (HIV-1). Reaction of thiourea withethyl arylmethylacetoacetatesfurnished5-alkyl-6-(arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines whichwere thenalkylated at the sulfur atom to afford the required 2-alkylthio or2-cycloalkylthio derivatives(S-DABOs). Chemical modifications at N-3, C-4, and C-6of the pyrimidine ring were attemptedwith the aim of improving antiretroviral activity. In particular,replacement of the benzylgroup with the 1-naphthylmethyl moiety enhanced the activity ofS-DABOs, whereas N-3alkylation and CO transformation into CS at position 4 of thepyrimidine ring led tocompounds devoid of anti-HIV-1 activity. Lower activity wasgenerally observed when1-naphthylmethyl was replaced by the isomeric 2-naphthylmethyl moiety.The most activecompounds showed activity in the low micromolar range withEC50 values comparable to thatof nevirapine.
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