Indole-based allosteric inhibitors of HIV-1 integrase.

Basic Information

ID: ALA4431384

Journal: Bioorg Med Chem Lett

Title: Indole-based allosteric inhibitors of HIV-1 integrase.

Authors: Patel PA, Kvaratskhelia N, Mansour Y, Antwi J, Feng L, Koneru P, Kobe MJ, Jena N, Shi G, Mohamed MS, Li C, Kessl JJ, Fuchs JR.

Abstract: Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.

CiteXplore: 27568085

DOI: 10.1016/j.bmcl.2016.08.037

Patent ID: