Design and synthesis of statine-containing BACE inhibitors

被引：36

作者：

Hu, JD ^{[1
]}

Cwi, CL ^{[1
]}

Smiley, DL ^{[1
]}

Timm, D ^{[1
]}

Erickson, JA ^{[1
]}

McGee, JE ^{[1
]}

Yang, HC ^{[1
]}

Mendel, D ^{[1
]}

May, PC ^{[1
]}

Shapiro, M ^{[1
]}

McCarthy, JR ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

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

关键词：

D O I：

10.1016/j.bmcl.2003.09.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Utilizing structure-based techniques and solid-phase synthesis, statine-based tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide BACE transition-state mimetic, 1, as the starting point. Structure-activity relationship studies at the P-3, P-2, and P-2' positions as well as the N-terminal capping group on scaffold 5 led to the discovery of potent inhibitors 27, 32, and 34 (IC50 < 100 nM). In addition, computational analysis and the X-ray structure of BACE-inhibitor 38 are discussed. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：4335 / 4339

页数：5

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