Synthesis and Anti-HIV-1 Activity of 4,5,6,7-Tetrahydro-5-methylimidazobenzodiazepin-2(1H)-one (TIBO) Derivatives

Article abstract of DOI:10.1021/jm00106a040

A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo<4,5,1-jk><1,4>benzodiazepin-2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells.Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products.A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group.The best analogue, 9jj, inhibited HIV-1 with an IC₅₀ of 4 μM, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.