Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592962 | Bioorganic & Medicinal Chemistry Letters | 2014 | 6 Pages |
Abstract
We have previously reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. While these inhibitors exhibited potent activities in enzymatic and cellular assays (KMI-429 in particular inhibited Aβ production in vivo), these inhibitors contained some natural amino acids that seemed to be required to improve enzymatic stability in vivo and permeability across the blood-brain barrier, so as to be practical drug. Recently, we synthesized non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold at the P2 position. Herein we report the SAR study of BACE1 inhibitors possessing this heterocyclic scaffold, a chelidonic or 2,6-pyridinedicarboxylic moiety.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Yoshio Hamada, Kenji Suzuki, Tomoya Nakanishi, Diganta Sarma, Hiroko Ohta, Ryoji Yamaguchi, Moe Yamasaki, Koushi Hidaka, Shoichi Ishiura, Yoshiaki Kiso,