Nitroimidazoles Part 8. Synthesis and Anti-HIV Activity of New 4-Nitroimidazole Derivatives Using the Suzuki Cross-Coupling Reaction

The development of new HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating structures of increased potency. To this end, a series of 1-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-4-(1,1'-biaryl)-4-yl-piperazine derivatives (6a-I) was synthesized via the Suzuki coupling reaction. Analogously, coupling of the acid derivative 5, prepared from 4, with various amino acid methyl esters in the presence of HOBt/DCC reagents afforded the benzamide derivatives 8-11. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compound 6f which showed inhibition of HIV-1 with EC50 = 2.60 mu g mL(-1) with a selectivity index (SI) of 9.