IMIDAZO[1,5-G][1,4]DIAZEPINES, TIBO ANALOGS LACKING THE PHENYL RING -SYNTHESIS AND EVALUATION AS ANTI-HIV AGENTS

The imidazo[1,5-g][1,4]diazepine derivatives 7a and 7b, analogues of T IBO lacking the aromatic ring, were prepared as part of a research pro gram 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 compou nds 10a-c and 16a-e. The hydroxyl group in these intermediates was act ivated 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 S-8. In vitro evaluation of compound s 7a,b and 13a,b in cell culture (GEM SS/HIV-1-LAI and CEM SS/HIV 1 ne virapine resistant cells) revealed that only 13b displayed minimal act ivity. Copyright (C) 1996 Elsevier Science Ltd