Design of gp120 HIV-1 entry inhibitors by scaffold hopping via isosteric replacements

We present the development of alternative scaffolds and validation of their synthetic pathways as a tool for the exploration of new HIV gp120 inhibitors based on the recently discovered inhibitor of this class, NBD-14136. The new synthetic routes were based on isosteric replacements of the amine and acid precursors required for the synthesis of NBD-14136, guided by molecular modeling and chemical feasibility analysis. To ensure that these synthetic tools and new scaffolds had the potential for further exploration, we eventually tested few representative compounds from each newly designed scaffold against the gp120 inhibition assay and cell viability assays. (C) 2021 Published by Elsevier Masson SAS.

Automated summary

Development of alternative scaffolds and validation of synthetic pathways as tools for exploring new HIV gp120 inhibitors based on NBD-14136. New synthetic routes were guided by molecular modeling and chemical analysis, and representative compounds were tested for inhibition and cell viability.