Synthesis and Antiplatelet Activity of New Imidazole-4-Carboxylic Acid Derivatives

✍ Scribed by Klaus Rehse; Jens Steege

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 146 KB
• Volume: 338
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200500150

✦ Synopsis

Abstract

1‐Arylalkyl‐5‐phenylsulfonamino‐imidazole‐4‐carboxylic acid esters and their carboxamides with an additional secondary amino group were synthesized and identified as antiplatelet agents in a low micromolar range (Born‐test, inducer collagen). To describe the mechanism of action more precisely the Born‐test was carried out as well with ADP, adrenaline or PAF, respectively. In addition, two compounds were investigated for their COX‐1 inhibitory activities. Provided the essential structural criteria are met i.e. amide group or ester, sulfonylamino rest, hydrophobic moieties, and a secondary amino function, slight structural modifications are able to shift the pattern of activity among the above platelet receptors. So, the ester 5c exhibits PAF antagonistic activity at IC~50~ = 1 μM and COX‐1 inhibition (IC~50~ = 0.4 μM). The carboxamide 6c shows ADP antagonistic properties (IC~50~ = 2 μM). Compound 6g is as well PAF antagonistic (IC~50~ = 4 μM) and a COX‐1 inhibitor (IC~50~ = 1 μM). The derivative 6i shows a strong antiadrenergic (IC~50~ = 0.15 μM) and PAF antagonistic (IC~50~ = 0.66 μM) effect.