Discovery of N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamides as potent and selective inhibitors of tumor necrosis factor-α converting enzyme (TACE)

被引：41

作者：

Duan, JJW ^{[1
]}

Lu, ZH ^{[1
]}

Xue, CB ^{[1
]}

He, XH ^{[1
]}

Seng, JL ^{[1
]}

Roderick, JJ ^{[1
]}

Wasserman, ZR ^{[1
]}

Liu, RQ ^{[1
]}

Covington, MB ^{[1
]}

Magolda, RL ^{[1
]}

Newton, RC ^{[1
]}

Trzaskos, JM ^{[1
]}

Decicco, CP ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(03)00313-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

New inhibitors of tumor necrosis factor-a converting enzyme (TACE) were discovered using an N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamide scaffold. The series was found to be potent in a porcine TACE (pTACE) assay with IC50S typically below 5 nM. For most compounds, selectivity for pTACE relative to MMP-1,-2, and -9 is at least 300-fold. Compound 2o was potent in inhibition of TNFalpha production in a human whole blood assay (WBA) with an IC50 of 0.42 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：2035 / 2040

页数：6

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