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Synthesis and Antiplatelet Activity of New Imidazole‐4‐Carboxylic Acid Derivatives
Author(s) -
Rehse Klaus,
Steege Jens
Publication year - 2005
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200500150
Subject(s) - chemistry , carboxylic acid , amide , carboxamide , stereochemistry , imidazole , platelet activating factor , platelet , aryl , inhibitory postsynaptic potential , chemical synthesis , in vitro , alkyl , biochemistry , organic chemistry , medicine , immunology , biology , neuroscience
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.