作者
Christopher J Fritschi, Shuaiyi Liang, Mohammadjavad Mohammadi, Saumya Anang, Francesca Moraca, Junhua Chen, Navid Madani, Joseph G Sodroski, Cameron F Abrams, Wayne A Hendrickson, Amos B Smith III
发表日期
2021/10/29
期刊
ACS medicinal chemistry letters
卷号
12
期号
11
页码范围
1824-1831
出版商
American Chemical Society
简介
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.
学术搜索中的文章
CJ Fritschi, S Liang, M Mohammadi, S Anang… - ACS medicinal chemistry letters, 2021