BACE-1 inhibitors part 2: Identification of hydroxy ethylamines (HEAs) with reduced peptidic character

被引：45

作者：

Clarke, Brian ^{[1
]}

Demont, Emmanuel ^{[1
]}

Dingwall, Colin ^{[1
]}

Dunsdon, Rachel ^{[1
]}

Faller, Andrew ^{[1
]}

Hawkins, Julie ^{[1
]}

Hussain, Ishrut ^{[1
]}

MacPherson, David ^{[1
]}

Maile, Graham ^{[1
]}

Matico, Rosalie ^{[1
]}

Milner, Peter ^{[1
]}

Mosley, Julie ^{[1
]}

Naylor, Alan ^{[1
]}

O'Brien, Alistair ^{[1
]}

Redshaw, Sally ^{[1
]}

Riddell, David ^{[1
]}

Rowland, Paul ^{[1
]}

Soleil, Virginie ^{[1
]}

Smith, Kathrine J. ^{[1
]}

Stanway, Steven ^{[1
]}

Stemp, Geoffrey ^{[1
]}

Sweltzer, Sharon ^{[1
]}

Theobald, Pam ^{[1
]}

Vesey, David ^{[1
]}

Walter, Daryl S. ^{[1
]}

Ward, John ^{[1
]}

Wayne, Gareth ^{[1
]}

机构：

[1] GloxoSmithKlin R&D, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 03期

关键词：

Alzheimer; BACE-1; aspartic protease; hydroxy ethylamine;

D O I：

10.1016/j.bmcl.2007.12.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P'(1), and P'(2) substituents, two different binding modes were observed in X-ray co-crystal structures. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1017 / 1021

页数：5

共 5 条

[1] Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2P3 moieties [J].