一系列氨基哌啶作为新型诱导型一氧化氮合酶抑制剂的发现。
Discovery of a series of aminopiperidines as novel iNOS inhibitors.
作者信息
Le Bourdonnec Bertrand, Leister Lara K, Ajello Christopher A, Cassel Joel A, Seida Pamela R, O'Hare Heather, Gu Minghua, Chu Guo-Hua, Tuthill Paul A, DeHaven Robert N, Dolle Roland E
机构信息
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA.
出版信息
Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43. doi: 10.1016/j.bmcl.2007.10.073. Epub 2007 Oct 25.
Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.
一氧化氮（NO）是多种生理和病理生理过程的介质，由一氧化氮合酶（NOS）的三种同工酶合成。潜在的临床候选药物应无抑制内皮型一氧化氮合酶（eNOS）的活性，因为eNOS在维持正常血压和血流中起重要作用。从高通量筛选的先导化合物中鉴定出一系列新型氨基哌啶作为诱导型一氧化氮合酶（iNOS）的强效抑制剂。通过这项研究，我们确定化合物33是一种强效的iNOS抑制剂，对eNOS的选择性大于25倍，对神经元型一氧化氮合酶（nNOS）的选择性为16倍。
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