Imidazo[1,5-g][1,4]diazepines, TIBO analogues lacking the phenyl ring: Synthesis and evaluation as Anti-HIV agents

Article abstract of DOI:10.1016/S0040-4020(96)00952-0

The imidazo[1,5-g][1,4]diazepine derivatives 7a and 7b, analogues of TIBO lacking the aromatic ring, were prepared as part of a research program to find compounds displaying antiviral activity against HIV-2 and resistant strains of HIV-1. Condensation of N-trityl and N-tosyl 4-(2-chloroethyl)imidazole with the appropriate amino alcohols gave compounds 10a-e and 16a-e. The hydroxyl group in these intermediates was activated toward closure of the [1,4]diazepine ring by either conversion to the corresponding chloro derivative, or by N → O transfer of the tosyl group. However, only cyclization to compounds 13a and 13b proved efficient. These products were converted to the target molecules 7 by reaction of their C-2 anion with Sg. In vitro evaluation of compounds 7a,b and 13a,b in cell culture (GEM SS/HIV-1-LAI and CEM SS/HIV 1 nevirapine resistant cells) revealed that only 13b displayed minimal activity.