Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds

Several thiazolyl thiourea derivatives were designed and synthesized as non -nucleoside inhibitors (NNRTI) of HIV-1 reverse transcriptase. Six lead com pounds were identified that showed subnanomolar IC50 values for the inhibit ion of HIV replication, were minimally toxic to human peripheral blood mono nuclear cells (PBMC) with CC50 values ranging from 28 to >100 muM, and show ed remarkably high selectivity indices ranging from 28,000 to >100,000. The most promising compound was N-[1-(1-furoylmethyl)]-N'-[2-(thiazolyl)]thiou rea (compound 6), which showed potency against two NNRTI-resistant HIV-1 is olates (A17 and A17 variant) at nanomolar to low micromolar concentrations, exhibited much greater potency against both wild-type as well as NNRTI-res istant HIV-1 than nevirapine, delavirdine, HI-443, and HI-244, was minimall y toxic to PBMC, and had a selectivity index of >100,000. The potency and m inimal cytotoxicity of these aromatic/heterocyclic thiourea compounds sugge st that they may be potentially useful as anti-AIDS drugs. (C) 2001 Publish ed by Elsevier Science Ltd.