2. Academic Validation
  3. Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1-phenylpiperazine scaffold

Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1-phenylpiperazine scaffold

  • Bioorg Med Chem Lett. 2014 Mar 15;24(6):1557-61. doi: 10.1016/j.bmcl.2014.01.070.
Jian-Min Jia 1,  Fang Liu 1,  Xiao-Li Xu 1,  Xiao-Ke Guo 1,  Fen Jiang 1,  Bahidja Cherfaoui 1,  Hao-Peng Sun 2,  Qi-Dong You 3
Affiliations

Affiliations

  • 1 Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sunhaopeng@163.com.
  • 3 Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqidong@gmail.com.
PMID: 24582477 DOI: 10.1016/j.bmcl.2014.01.070
Abstract

Previously, we identified 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol (1) as a novel HSP90 Inhibitor with moderate activity through virtual screening. In this study, we report the optimization process of 1. A series of analogues containing the 1-phenylpiperazine core scaffold were synthesized and evaluated. The structure-activity relationships (SAR) for these compounds was also discussed for further molecular design. This effort afforded the most active inhibitor 13f with improved activity in not only target-based level, but also cell-based level compared with the original hit 1.

Keywords

Hsp90 inhibitors; Structure-based drug design; Structure–activity relationships.

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