Indole-based allosteric inhibitors of HIV-1 integrase. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Patel, Pratiq A.; Kvaratskhelia, Nina; Mansour, Yara; Antwi, Janet; Feng, Lei; Koneru, Pratibha; Kobe, Mathew J.; Jena, Nivedita; Shi, Guqin; Mohamed, Mosaad S.; Li, Chenglong; Kessl, Jacques J.; Fuchs, James R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 19(2016)
• Page Start: 4748
• Page End: 4752
• Publication Date: 2016-10-01
• Subjects: HIV integrase inhibitor -- ALLINI -- Scaffold hopping; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.08.037
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 = 4.5 μM) 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.