Synthesis and anti-HIV-1 activity evaluation of 5-alkyl-2-alkylthio-6-(arylcarbonyl or α-cyanoarylmethyl)-3,4-dihydropyrimidin-4(3H)-ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of novel S-DABO analogues (S-DABOs, 1) were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Key structural modifications included replacement of the 6-arylmethyl group by a 6-arylcarbonyl or 6-(alpha-cyanoarylmethyl) group. Most of the compounds showed only micromolar potency against HIV-1 in MT-4 cells in vitro, though two of them (3e and 3g) were unusually potent (IC50 = 0.09 and 0.002 mu M, respectively) and selective (SI = 1500 and 4600, respectively). Structure-activity relationships among the newly synthesized S-DABOs are discussed.