Novel nanomolar imidazo[4,5-b]pyridines as selective nitric oxide synthase (iNOS) inhibitors: SAR and structural insights

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Graedler, Ulrich¹  Fuchss, Thomas¹  Ulrich, Wolf-Ruediger¹  Boer, Rainer¹  Strub, Andreas¹  Hesslinger, Christian¹  Anezo, Celine¹  Diederichs, Kay²  Zaliani, Andrea¹ 

[1] Nycomed GmbH, D-78467 Constance, Germany

[2] Univ Konstanz, Fachbereich Biol, D-78457 Constance, Germany

关键词: Nitric oxide synthase;    Inflammation;    Crystal structure;    Structure-based design;    Selectivity;    Inhibitor;   

DOI  :  10.1016/j.bmcl.2011.05.073

来源: Elsevier

【 摘 要 】

Inducible arginine oxidation and subsequent NO production by correspondent synthase (iNOS) are important cellular answers to proinflammatory signals. Prolonged NO production has been proved in higher organisms to cause stroke or septic shock. Several classes of potent NOS inhibitors have been reported, most of them targeting the arginine binding site of the oxygenase domain. Here we disclose the SAR and the rational design of potent and selective iNOS inhibitors which may be useful as anti-inflammatory drugs. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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