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
  • 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: [email protected].
  • 3. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: [email protected].
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.