2. Academic Validation
  3. 4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: synthesis, biological evaluation and docking studies

4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: synthesis, biological evaluation and docking studies

  • Eur J Med Chem. 2014 May 22:79:413-21. doi: 10.1016/j.ejmech.2014.04.025.
Peng Liu 1,  Yan Niu 2,  Chao Wang 1,  Qi Sun 1,  Yaya Zhai 1,  Jiapei Yu 1,  Jing Sun 1,  Fengrong Xu 1,  Gang Yan 1,  Wenjie Huang 1,  Lei Liang 1,  Ping Xu 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
  • 2 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: yanniu@bjmu.edu.cn.
  • 3 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: pingxu@bjmu.edu.cn.
PMID: 24763262 DOI: 10.1016/j.ejmech.2014.04.025
Abstract

In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3-carboxamide derivatives as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 μM) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.

Keywords

4-Oxo-1,4-dihydro-quinoline-3-carboxamide; Alzheimer's disease; BACE-1 inhibitors; Docking study.

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