1. Academic Validation
  2. Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

  • Bioorg Med Chem. 2011 Aug 1;19(15):4601-7. doi: 10.1016/j.bmc.2011.06.007.
Xiao-Dong Ma 1 Xuan Zhang Hui-Fang Dai Shi-Qiong Yang Liu-Meng Yang Shuang-Xi Gu Yong-Tang Zheng Qiu-Qin He Fen-Er Chen
Affiliations

Affiliation

  • 1 Department of Chemistry, Fudan University, Shanghai 200433, PR China.
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.

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