Hydroxytriamides as potent γ-secretase inhibitors

被引：21

作者：

Prasada, CVC

Noonan, JW

Sloan, CP

Lau, W

Vig, S

Parker, MF

Smith, DW

Hansel, SB

Polson, CT

Barten, DM

Felsenstein, KM

Roberts, SB

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Drug Metab & Pharmacokinet, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Neurosci Biol, Wallingford, CT 06492 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 08期

关键词：

hydroxytriamides; gamma-secretase;

D O I：

10.1016/j.bmcl.2004.01.086

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a cell-based assay, we have identified optimal residues and key recognition elements necessary for inhibition of gamma-secretase. An (S)-hydroxy group or 3,5-difluorophenylacetyl group at the amino terminus and N-methyltertiary amide moiety at the carboxy terminus provided potent gamma-secretase inhibitors with an IC50 < 10 nM. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1917 / 1921

页数：5

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