Novel nanomolar imidazo[4,5-b]pyridines as selective nitric oxide synthase (iNOS) inhibitors: SAR and structural insights
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.
DOI:
10.1016/j.bmcl.2011.05.073
作为产物:
描述:
2-Benzylamino-4-(2-methoxyethoxy)-3-nitropyridine 在
钯sodium hydroxide 、 silica gel 作用下,
以
甲醇 、 盐酸 为溶剂,
反应 5.0h,
以gives 0.89 g of the title compound as a brownish oil的产率得到2,3-Diamino-4-(2-methoxyethoxy)pyridine
The compounds of formula (I) in which R1 is 1-4C-alkoxy, , A is 1-4C-alkylene, B represents 3H-imidazo (4,5b) pyridin-2-yl, 3H-imidazo (4,5-b) pyridin-2-yl substituted by R2 and/or R8, 9H-purin-8yl or 9H-purin-8-yl substituted by R4 and/or R5 are effective iNOS inhibitors.
The compounds of formula I
in which R1 is 1-4C-alkoxy, A is 1-4C-alkylene, B represents 3H-imidazo[4,5-b]pyridin-2-yl, 3H-imidazo[4,5-b]pyridin-2-yl substituted by R2 and/or R3, 9H-purin-8-yl or 9H-purin-8-yl substituted by R4 and/or R5, are effective iNOS inhibitors.