[Synthesis and platelet aggregation inhibitory activity of analogues of 4-([2-(1H-imidazol-1-yl)-1-(4-substituted-phenyl)ethoxy]methyl)benzoic acids].
Analogues of 4-([2-(1H-imidazol-1-yl)-1-(4-substituted-phenyl)ethoxy]methyl)benz oic acids were synthesized for searching of more potent and selective thromboxane synthetase inhibitors. All title compounds are first reported. Results of preliminary pharmacological tests showed that all title compounds have activity against thromboxane synthetase, i.e. inhibiting platelet aggregation induced by AA in vitro with rabbit. Compound 15 is the most potent. Its activity is 55.6% of that of Dazoxiben in comparison of IC50. The change of group substituted on benzene would affect inhibitory activity to thromboxane synthetase. Esters are more potent than the parent acids. This is probably due to the greater platelet permeability of the more lipophilic ester prior to intraplatelet deesterification. NBS was applied to the preparation of p-bromoethylbenzoic ester. This method increased the yield and simplified operating process.
Wu
Q Y
QY
Department of Medicinal Chemistry, College of Pharmacy, Second Military Medical University, Shanghai.
Yang
J Q
JQ
D000818:Animals; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D013930:Thromboxane-A Synthase