Nicotinyl aspartyl ketones as inhibitors of caspase-3

被引：23

作者：

Isabel, E

Black, WC

Bayly, CI

Grimm, EL

Janes, MK

McKay, DJ

Nicholson, DW

Rasper, DM

Renaud, J

Roy, S

Tam, J

Thornberry, NA

Vaillancourt, JP

Xanthoudakis, S

Zamboni, R

机构：

[1] Merck Frosst Canada Inc, Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

[2] Merck Res Labs, Rahway, NJ 07065 USA

来源：

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

关键词：

D O I：

10.1016/S0960-894X(03)00390-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact in the treatment of several degenerative diseases. Since P, aspartic acid is a required element of recognition for this enzyme, a library of capped aspartyl aldehydes was synthesized using solid-phase chemistry. The 5-bromonicotinamide derivative of the aspartic acid aldehyde was identified to be an inhibitor of caspase-3. Substitution at the 5-position of the pyridine ring and conversion of the aldehyde to ketones led to a series of potent inhibitors of caspase-3. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：2137 / 2140

页数：4

共 9 条

[1] SYNTHESIS AND BEHAVIOR OF NADH MODELS BEARING A CHIRAL SULFOXIDE [J].