title: Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy.
abstract: Molecular hybridization of the known anti-HIV-1 template DPC083 and etravirine based on docking model overlay has been generated a novel series of diarylbenzopyrimidine analogues (DABPs) (5a-z). These new hybrids were assessed for their activity against HIV in MT-4 cell cultures. Most of these compounds showed good activity against wild-type HIV-1 and mutant viruses. In particular, compound 5r showed the most potent activity against wild-type HIV-1 with an EC50 value of 1.8 nM, and with a selectivity index up to 111,954. It also proved more active against mutant L100I, K103N, Y188L, and K103N+Y181C RT HIV-1 strains than efavirenz.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Zhao-Sen
authors.initials: ZS
authors.lastname: Zeng
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: He
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Feng
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D009570:Nitriles; D011485:Protein Binding; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; C430648:DPC 083; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011799:Quinazolines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D054303:HIV Reverse Transcriptase