Novel 1,3-dihydro-benzimidazol-2-ones and their analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of novel benzimidazolones and their analogues, characterized by the presence of one or more methyl groups or Other bioisosteric moieties at different positions of the phenyl ring at N-1, were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Most of the new compounds proved to be highly effective in inhibiting both HIV-1 replication in MT4 cells with minimal cytotoxicity and RT Enzyme at nanomolar concentrations. Some derivatives were also tested against RTs containing single amino acid mutations responsible for resistance to non-nucleoside Reverse Transcriptase inhibitors (NNRTIs). The different potencies displayed by the new compounds were studied using molecular modeling.