title: Pyrazolo[1,5-a]pyrimidine-based macrocycles as novel HIV-1 inhibitors: a patent evaluation of WO2015123182.
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.
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010330:Patents as Topic; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011720:Pyrazoles; D011743:Pyrimidines; C527752:pyrazolo(1,5-a)pyrimidine
keywords: AIDS; HIV-1; cART; drug design; drug resistance; macrocycle; protein-protein interactions