1229575-97-6Relevant academic research and scientific papers
Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors
Choi, Soo-Jeong,Cho, Joong-Heui,Im, Isak,Lee, So-Deok,Jang, Ji-Yeon,Oh, Yu-Min,Jung, Yong-Keun,Jeon, Eun-Seok,Kim, Yong-Chul
experimental part, p. 2578 - 2590 (2010/07/08)
BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30?μM, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors.
