2. Academic Validation
  3. The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors

The structural modification and biological evaluation of tetrahydrothienopyridine derivatives as selective BChE inhibitors

  • Bioorg Med Chem Lett. 2023 Sep 1;93:129436. doi: 10.1016/j.bmcl.2023.129436.
Tingkai Chen 1,  Shenghu Sang 2,  Yuqing Wei 2,  Yujie Ge 2,  Jisheng Jin 2,  Yaoyao Bian 3,  Yuqiong Pei 2,  Nianguang Li 4,  Haopeng Sun 5,  Yao Chen 6
Affiliations

Affiliations

  • 1 School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 2 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3 Jiangsu Provincial Engineering Center of TCM External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 4 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: linianguang@njucm.edu.cn.
  • 5 School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: sunhaopeng@cpu.edu.cn.
  • 6 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: 300630@njucm.edu.cn.
PMID: 37549853 DOI: 10.1016/j.bmcl.2023.129436
Abstract

A series of tetrahydrothienopyridine derivatives have been designed, synthesized, and evaluated as selective BChE inhibitors. Compounds were analyzed via HRMS, 1H NMR, and 13C NMR. The inhibitory effects were evaluated according to the method of Ellman et al. 6n was the most potent and selective inhibitor against BChE (eeAChE IC50 = 686.4 ± 478.6 μM, eqBChE IC50 = 10.5 ± 5.0 nM, SI = 6.5*104, hBChE IC50 = 32.5 ± 6.5 nM). Cell-based assays have confirmed the low neurotoxicity of 6a and 6n and their moderate neuroprotective effects. Compounds 6a and 6n provide novel chemical entities for the treatment of Alzheimer's disease.

Keywords

Alzheimer's disease; BChE inhibitor; Tetrahydrothienopyridine.

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