title: Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: A novel series of benzophenone derivatives with B-ring substituted by naphthyl ring has been synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Most of these compounds showed good to moderate activity against wild-type HIV-1 and mutated viruses. In particular, the analogue 10i demonstrated the most potent activity against wild-type HIV-1 with an EC₅₀ value of 4.8 nM, and with a high selectivity index up to 10347.9, it also proved to be active against the HIV-1 double mutant strain A₁₇ (K103N+Y181C) with an EC₅₀ value of 2.1 μM. In addition, the molecular modeling study was used to explore the major interactions between the potent inhibitors with the HIV-1 RT. The investigation of the structure-activity relationships may serve as an important lead for the further optimization.
authors: Department of Chemistry, Fudan University, Shanghai 200433, PR China.
authors: Xiao-Dong
authors: XD
authors: Ma
authors: Xuan
authors: X
authors: Zhang
authors: Hui-Fang
authors: HF
authors: Dai
authors: Shi-Qiong
authors: SQ
authors: Yang
authors: Liu-Meng
authors: LM
authors: Yang
authors: Shuang-Xi
authors: SX
authors: Gu
authors: Yong-Tang
authors: YT
authors: Zheng
authors: Qiu-Qin
authors: QQ
authors: He
authors: Fen-Er
authors: FE
authors: Chen
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001577:Benzophenones; D018894:Reverse Transcriptase Inhibitors; C047723:benzophenone; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase