Synthesis and HIV-1 inhibition of novel benzimidazole derivatives

A range of novel benzimidazole derivatives, some bearing analogy to TIBO, have been synthesized, and evaluated for inhibition of HIV-1 infectivity. The most active and selective compounds are a series of N-alkoxy-2-alkyl-benzimidazoles, several having EC50< 10μM (one sub-micromolar at 600nM), and selectivity ratios of 10–167. The most selective benzimidazoles, 18a, 18c, show modest RT inhibition, and binding assays indicate gp 120-binding is not a target.