Synthesis and biological evaluation of new HIV-1 protease inhibitors with purine bases as P2-ligands

Mei Zhu; Biao Dong; Guo-Ning Zhang; Ju-Xian Wang; Shan Cen; Yu-Cheng Wang

doi:10.1016/j.bmcl.2019.03.049

Synthesis and biological evaluation of new HIV-1 protease inhibitors with purine bases as P2-ligands

Bioorg Med Chem Lett. 2019 Jun 15;29(12):1541-1545. doi: 10.1016/j.bmcl.2019.03.049. Epub 2019 Apr 3.

Authors

Mei Zhu¹, Biao Dong¹, Guo-Ning Zhang¹, Ju-Xian Wang¹, Shan Cen², Yu-Cheng Wang³

Affiliations

¹ Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
² Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: shancen@hotmail.com.
³ Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: wangyucheng@imb.pumc.edu.cn.

PMID: 31014912
DOI: 10.1016/j.bmcl.2019.03.049

Abstract

Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2'-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC₅₀ 43 nM, 42 nM and 68 nM in vitro, respectively.

Keywords: Biological evaluation; HIV-1 protease inhibitors; Purine bases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HIV Protease Inhibitors / pharmacology
HIV Protease Inhibitors / therapeutic use*
Humans
Ligands*
Molecular Structure
Purines / metabolism*

Substances

HIV Protease Inhibitors
Ligands
Purines