title: Synthesis, structure-activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors.
abstract: A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC(50) values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC(50) = 0.30 nM, TI = 184 578), 13l (EC(50) = 0.37 nM, TI = 212 819), 13m (EC(50) = 0.32 nM, TI = 260 617) and 13r (EC(50) = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC(50) values of 0.29 μM, 0.14 μM, 0.10 μM and 0.27 μM, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 μM concentration.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Ma
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: He
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shi-Qiong
authors.initials: SQ
authors.lastname: Yang
authors.forename: Liu-Meng
authors.initials: LM
authors.lastname: Yang
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Gu
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Dai
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005559:Formamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D005559:Formamides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase