Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1β converting enzyme (ICE or caspase 1)

被引：17

作者：

Galatsis, Paul ^{[1
]}

Caprathe, Bradley ^{[1
]}

Gilmore, John ^{[1
]}

Thomas, Anthony ^{[1
]}

Linn, Kristin ^{[1
]}

Sheehan, Susan ^{[1
]}

Harter, William ^{[1
]}

Kostlan, Catherine ^{[1
]}

Lunney, Elizabeth ^{[1
]}

Stankovic, Charles ^{[1
]}

Rubin, John ^{[1
]}

Brady, Kenneth ^{[2
]}

Allen, Hamish ^{[2
]}

Talanian, Robert ^{[2
]}

机构：

[1] Pfizer Global R&D, Ann Arbor, MI 48105 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期

关键词：

ICE inhibitor; P2-P3; replacement; Succinic acid amides; ANTIINFLAMMATORY DRUGS; CYSTEINE PROTEASE; PRALNACASAN; DISEASE; POTENT; IL-1;

D O I：

10.1016/j.bmcl.2010.07.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Succinic acid amides have been found to be effective P2-P3 scaffold replacements for peptidic ICE inhibitors. Heteroarylalkyl fragments occupying the P4 position provided access to compounds with nM affinities. Utilization of an acylal prodrug moiety was required to overcome biopharmaceutical issues which led to the identification of 17f, a potential clinical candidate. (C) 2010 Elsevier Ltd. All rights reserved.

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收藏

页码：5184 / 5190

页数：7

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