KMI-008, a novel β-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic:: Design and synthesis of substrate-based octapeptides

被引：87

作者：

Shuto, D

Kasai, S

Kimura, T

Liu, P

Hidaka, K

Hamada, T

Shibakawa, S

Hayashi, Y

Hattori, C

Szabo, B

Ishiura, S

Kiso, Y ^{[1
]}

机构：

[1] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Dept Med Chem, Yamashina Ku, Kyoto 6078412, Japan

[2] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Meguro Ku, Tokyo 1538902, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 24期

关键词：

D O I：

10.1016/j.bmcl.2003.09.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of substrate-based beta-secretase (BACEI) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized. Phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an effective transition-state mimic at the P, position. Structure-activity relationships (SARs) of the P-3-P-3' positions of BACE1 inhibitors were studied. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：4273 / 4276

页数：4

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