Significance of interactions of BACE1–Arg235 with its ligands and design of BACE1 inhibitors with P 2 pyridine scaffold

…, N Miyamoto, D Sarma, T Hamada, T Nakanishi…

Index: Hamada, Yoshio; Ohta, Hiroko; Miyamoto, Naoko; Sarma, Diganta; Hamada, Takashi; Nakanishi, Tomoya; Yamasaki, Moe; Yamani, Abdellah; Ishiura, Shoichi; Kiso, Yoshiaki Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 9 p. 2435 - 2439

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Citation Number: 22

Abstract

Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood–brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors ...