期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 3, 页码 1427-1432出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.12.028
关键词
Ischemia reperfusion injury; Jun N-terminal kinase inhibitor; Aminopurine; Structure-based drug design
In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury. (C) 2011 Elsevier Ltd. All rights reserved.
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