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

Journal of Medicinal Chemistry
2007.0

Abstract

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 0.23 [corrected] microM, respectively) and selective (SI=1500 and 1033 [corrected] respectively). Structure-activity relationships among the newly synthesized S-DABOs are discussed.

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