Rapid optimization of an ICE inhibitor synthesis using multiple reaction conditions in a parallel array

被引：27

作者：

Warmus, JS

Ryder, TR

Hodges, JC

Kennedy, RM

Brady, KD

机构：

[1] Warner Lambert Co, Parke Davis Pharmaceut Res, Dept Chem, Ann Arbor, MI 48105 USA

[2] BASF Biores Corp, Dept Biochem, Worcester, MA 01605 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 17期

关键词：

D O I：

10.1016/S0960-894X(98)00418-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimization of a 2-step reaction sequence was accomplished in 3-4 days, with over 200 different reaction conditions evaluated. Combinatorial arrays were performed using the optimized conditions to synthesize 590 new compounds which were tested for inhibition against N-His (D381E) ICE. Thirty-five compounds showed at least a tenfold improvement in activity compared to an initial standard. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：2309 / 2314

页数：6

共 7 条

[1]

ATOR MA, 1995, CURR PHARM DESIGN, V1, P191

[2]

BRAY AM, 1995, TETRAHEDRON LETT, V36, P5081

[3] Preparation of an autolysis-resistant interleukin-1 beta converting enzyme mutant [J].