Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3SAR

被引：48

作者：

Lamar, J ^{[1
]}

Hu, JD ^{[1
]}

Bueno, AB ^{[1
]}

Yang, HC ^{[1
]}

Guo, DQ ^{[1
]}

Copp, JD ^{[1
]}

McGee, J ^{[1
]}

Gitter, B ^{[1
]}

Timm, D ^{[1
]}

May, P ^{[1
]}

McCarthy, J ^{[1
]}

Chen, SH ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2003.09.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：239 / 243

页数：5

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