Potent small molecule inhibitors of spleen tyrosine kinase (Syk)

被引：74

作者：

Lai, JYQ ^{[1
]}

Cox, PJ ^{[1
]}

Patel, R ^{[1
]}

Sadiq, S ^{[1
]}

Aldous, DJ ^{[1
]}

Thurairatnam, S ^{[1
]}

Smith, K ^{[1
]}

Wheeler, D ^{[1
]}

Jagpal, S ^{[1
]}

Parveen, S ^{[1
]}

Fenton, G ^{[1
]}

Harrison, TKP ^{[1
]}

McCarthy, C ^{[1
]}

Bamborough, P ^{[1
]}

机构：

[1] Aventis Pharmaceut, Bridgewater, NJ 08807 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(03)00658-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of oxindoles demonstrating inhibition of the pbosphorylation of biotinylated substrates of Syk and IgE/FcepsilonRI triggered basophil cell degranulation has been identified. A study of the SAR around sulfonamide 31 (IC50=5 nM, EC50= 1400 nM) is discussed. The modest cellular activity representative of the sulfonamide series was overcome when the Polar surface Area was lowered to < 110 Angstrom(2), leading to the identification of amide 32 (IC50= 145 nM, EC50= 100 nM). (C) 2003 Published by Elsevier Ltd.

引用

页码：3111 / 3114

页数：4

共 12 条

[1]

BEAVEN MA, 1984, J BIOL CHEM, V259, P7129

[2]

CHAPMAN RF, 1986, HETEROCYCLES, V24, P3115

[3] Computational methods for the prediction of 'drug-likeness' [J].