Structural highlights
Publication Abstract from PubMed
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=4.5muM) 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.
Indole-based allosteric inhibitors of HIV-1 integrase.,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 Bioorg Med Chem Lett. 2016 Oct 1;26(19):4748-52. doi: 10.1016/j.bmcl.2016.08.037., Epub 2016 Aug 13. PMID:27568085[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Indole-based allosteric inhibitors of HIV-1 integrase. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4748-52. doi: 10.1016/j.bmcl.2016.08.037., Epub 2016 Aug 13. PMID:27568085 doi:http://dx.doi.org/10.1016/j.bmcl.2016.08.037
