Structure–activity relationship study of BACE1 inhibitors possessing a chelidonic or 2, 6-pyridinedicarboxylic scaffold at the P 2 position

…, R Yamaguchi, M Yamasaki, K Hidaka, S Ishiura…

Index: Hamada, Yoshio; Suzuki, Kenji; Nakanishi, Tomoya; Sarma, Diganta; Ohta, Hiroko; Yamaguchi, Ryoji; Yamasaki, Moe; Hidaka, Koushi; Ishiura, Shoichi; Kiso, Yoshiaki Bioorganic and Medicinal Chemistry Letters, 2014 , vol. 24, # 2 p. 618 - 623

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Citation Number: 7

Abstract

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 ...