Arylazolylthioacetanilide. Part 8: Design, synthesis and biological evaluation of Novel 2-(2-(2,4-Dichlorophenyl)-2H-1,2,4-triazol-3-ylthio)-N-arylacetamides As Potent HIV-1 inhibitors

The development of novel HIV-1 NNRTIs offers the possibility of generating novel structures with increased potency. Based on the bioisosteric principle, a novel series of 2-(2-(2,4-dichlorophenyl)-2H-1,2,4-triazol-3-ylthio)-N-arylacetamide derivatives were designed, synthesized using a simple and efficient synthetic route, structurally confirmed by spectral analysis, evaluated for their anti-HIV activity in MT-4 cells and their inhibitory effect on HIV-1 RT. The results showed that some of the new compounds displayed low micromolar potency for inhibiting HIV-1 replication and promising activities against several selected resistant strains that confer resistance to current NNRTIs. However, all newly synthesized derivatives were not active against HIV-2 replication.

Some newly synthesized 1,2,4-triazolacetamide derivatives displayed low micromolar potency for inhibiting HIV-1 replication and promising activities against several selected resistant strains that confer resistance to current NNRTIs.Figure optionsDownload as PowerPoint slideHighlights
► A facile synthetic approach towards novel 1,2,4-triazolacetamides was described.
► More than half of the tested compounds were found to be active against HIV-1.
► Some derivatives showed promising activities against several selected resistant strains.