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.
Compounds of a certain formula (I)
in which Ra and Rb have the meanings indicated in the description, are novel effective compounds with anti-proliferative and apoptosis inducing activity.
[EN] IMIDAZO[4,5-B]QUINOLINE-DERIVATIVES AND THEIR USE AS NO-SYNTHASE INHIBITORS<br/>[FR] DERIVES DE IMIDAZO[4,5-B]QUINOLINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE NO-SYNTHASE
申请人:ALTANA PHARMA AG
公开号:WO2004076451A1
公开(公告)日:2004-09-10
The compounds of formula I In which R1, R2, R3 and A have the meanings as given In the description are novel effective INOS Inhibitors.
[EN] IMIDAZOPYRIDINE-DERIVATIVES AS INDUCIBLE NO-SYNTHASE INHIBITORS<br/>[FR] DERIVES D'IMIDAZOPYRIDINE UTILISES COMME INHIBITEURS INDUCTIBLES DE LA NO SYNTHASE
申请人:ALTANA PHARMA AG
公开号:WO2005030769A1
公开(公告)日:2005-04-07
The compounds of formula (I) in which R1, R2, Het1 and A have the meanings as given in the description are novel effective iNOS inhibitors.
The compounds of formula (I) in which R1 is 1-4C-alkoxy, , A is 1-4C-alkylene, B represents 3H-imidazo (4,5b) 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.