Design, synthesis and biological evaluation of HIV-1 protease inhibitors with morpholine derivatives as P2 ligands in combination with cyclopropyl as P1′ ligand. Issue 7 (1st April 2020)

• Record Type: Journal Article
• Authors: Dou, Yue; Zhu, Mei; Dong, Biao; Wang, Ju-Xian; Zhang, Guo-Ning; Zhang, Fan; Wang, Yu-Cheng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 7(2020)
• Publication Date: 2020-04-01
• Subjects: HIV-1 protease inhibitors -- Morpholine -- Cyclopropyl -- Synthesis -- Biological evaluation -- Molecular modeling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127019
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Inhibitor m18 exhibited excellent enzyme inhibitory potency (IC50 = 47 nM). Morpholine as the P2 ligands and cyclopropyl as the P1′ ligand at the meantime in this study. The computational docking of m1 was measured. Abstract: A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1′ ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC50 value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study.