130818-96-1Relevant articles and documents
Identification of a potent, selective, and orally active leukotriene A 4 hydrolase inhibitor with anti-inflammatory activity
Grice, Cheryl A.,Tays, Kevin L.,Savall, Brad M.,Wei, Jianmei,Butler, Christopher R.,Axe, Frank U.,Bembenek, Scott D.,Fourie, Anne M.,Dunford, Paul J.,Lundeen, Katherine,Coles, Fawn,Xue, Xiaohua,Riley, Jason P.,Williams, Kacy N.,Karlsson, Lars,Edwards, James P.
experimental part, p. 4150 - 4169 (2009/07/19)
LTA4H is a ubiquitously distributed 69 kDa zinc-containing cytosolic enzyme with both hydrolase and aminopeptidase activity. As a hydrolase, LTA4H stereospecifically catalyzes the transformation of the unstable epoxide LTA4 to the diol LTB4, a potent chemoattractant and activator of neutrophils and a chemoattractant of eosinophils, macrophages, mast cells, and T cells. Inhibiting the formation of LTB4 is expected to be beneficial in the treatment of inflammatory diseases such as inflammatory bowel disease (IBD), asthma, and atherosclerosis. We developed a pharmacophore model using a known inhibitor manually docked into the active site of LTA4H to identify a subset of compounds for screening. From this work we identified a series of benzoxazole, benzthiazole, and benzimidazole inhibitors. SAR studies resulted in the identification of several potent inhibitors with an appropriate cross-reactivity profile and excellent PK/PD properties. Our efforts focused on further profiling JNJ 27265732, which showed encouraging efficacy in a disease model relevant to IBD.
N-(AMIDINOPHENYL) CYCLOUREA ANALOGS AS FACTOR XA INHIBITORS
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, (2008/06/13)
The present application describes N-(amidinophenyl)cyclourea analogs of formula I: STR1 which are useful as inhibitors of factor Xa.
Molecular features associated with polyamine modulation of NMDA receptors
Lewin, Anita H.,Fudala, Louise,Navarro, Hernan,Zhou, Li-Ming,Popik, Piotr,Faynsteyn, Alexander,Skolnick, Phil
, p. 988 - 995 (2007/10/03)
The effect of 1,3-diamines on basal and spermine-stimulated [3H]MK-801 binding was investigated. Systematic variations in the molecular parameters revealed that, in general, lipophilic 1,3-diamines inhibited and hydrophilic 1,3-diamines enhance