Indoles and pyridazino[4,5-b]indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase

Summary The synthesis and the study of the activity of new indol-2-carboxamides and pyridazino[4,5- b ]indoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented. The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y 181C and P236L/Y181C) was evaluated. The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1 IIIB -infected HT4lacZ-1 cells. Their potential cytotoxicity was determined in parallel. Two lead compounds, N -[1-[2-(3-isopropylamino)pyridyl]piperazin]-5,6-methylenedioxy indol-2-carboxamide 7q and N -[1-[2-(3-ethylamino)pyridyl]piperazin]-5,6-methylenedioxyindol-2-carboxamide 7s have been identified.