Download MendeleyIndole-based allosteric inhibitors of HIV-1 integrase.
Patel, P.A., Kvaratskhelia, N., Mansour, Y., Antwi, J., Feng, L., Koneru, P., Kobe, M.J., Jena, N., Shi, G., Mohamed, M.S., Li, C., Kessl, J.J., Fuchs, J.R.(2016) Bioorg Med Chem Lett 26: 4748-4752
- PubMed: 27568085
- DOI: https://doi.org/10.1016/j.bmcl.2016.08.037
- Primary Citation of Related Structures:
5KGW, 5KGX - PubMed 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.
Organizational Affiliation:
Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; Department of Chemistry, The Ohio State University, Columbus, OH 43210, United States.
