Pyrazolo[1, 5-a]pyrimidine-based macrocycles as novel HIV-1 inhibitors: a patent evaluation of WO2015123182. (1st September 2016)

• Record Type: Journal Article
• Authors: Sun, Lin; Gao, Ping; Zhan, Peng; Liu, Xinyong
• Is Part Of: Expert opinion on therapeutic patents. Volume 26:Number 9(2016:Sep.)
• Page Start: 979
• Page End: 986
• Publication Date: 2016-09-01
• Subjects: HIV-1 -- AIDS -- drug resistance -- cART -- drug design -- macrocycle -- protein-protein interactions; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2016.1210127
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: The emergence of drug resistance in Combination Antiretroviral Therapy (cART) confirms a continuing need to investigate novel HIV-1 inhibitors with unexplored mechanisms of action. Recently, a series of pyrazolopyrimidine-based macrocyclic compounds were reported as inhibitors of HIV-1 replication disclosed in the patent WO2015123182. Most of the disclosed compounds possessed in vitro antiviral potency in single-digit nanomolar range, which were determined by MT-2 cell assay. Then, the structural diversity, pharmacophore similarity of HIV-1 IN-LEDGF/p75 inhibitors, and implications for drug design were analyzed. In the end of this article, a glimpse of some macrocycles as potent antiviral agents (drug candidates) was provided. Some strategies and technologies enabling macrocycle design were also described. We expect that further development of these macrocyclic compounds will offer new anti-HIV-1 drug candidates.