کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370100 | 981807 | 2016 | 6 صفحه PDF | دانلود رایگان |
Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-l-cyclohexylalanine-l-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-l-cyclohexylalanine-l-isoleucine-2-methoxybenzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+ (IC50 0.5 μM) in human colon cells, IL-6 and TNFα secretion (IC50 1–5 μM) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED50 5 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity.
Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 3, 1 February 2016, Pages 986–991