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Publication Abstract from PubMed

The design and synthesis of butyl chain derivatives at the indane ring 3-position of our lead CD4-mimetic compound BNM-III-170 that inhibits human immunodeficiency virus (HIV-1) infection are reported. Optimization efforts were guided by crystallographic and computational analysis of the small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120. Biological evaluation of 11-21 revealed that members of this series of CD4-mimetic compounds are able to inhibit HIV-1 viral entry into target cells more potently and with greater breadth compared to BNM-III-170. Crystallographic analysis of the binding pocket of 14, 16, and 17 revealed a novel hydrogen bonding interaction between His105 and a primary hydroxyl group on the butyl side chain. Further optimization of this interaction with the His105 residue holds the promise of more potent CD4-mimetic compounds.

Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics.,Fritschi CJ, Liang S, Mohammadi M, Anang S, Moraca F, Chen J, Madani N, Sodroski JG, Abrams CF, Hendrickson WA, Smith AB 3rd ACS Med Chem Lett. 2021 Oct 29;12(11):1824-1831. doi: , 10.1021/acsmedchemlett.1c00437. eCollection 2021 Nov 11. PMID:34795873^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.