Synthesis and pharmacological characterization of bicyclo[2.2.1]heptyl-interphenylene thromboxane antagonists

• Main Author: 郭浩蓁
• Other Authors: W.M. Kan
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/63768293705894580040

碩士 === 國立成功大學 === 藥理學研究所 === 86 === Thromboxane A2 is involved in thrombi formation. It is related to many cardiovascular diseases. Activation of the platelet thromboxane receptor leads to platelet aggregation and secretion of more thromboxane A2. Increase in thromboxane A2 causes vascular contraction. Abnormal platelet receptor activation may be related to thrombosis and atherosclerosis. On the contrary, activation of endothelial thromboxane receptor leads to an increase in production of prostacyclin that opposes thromboxane action. Therefore, selective inhibition of the platelet type receptor may be beneficial in the prevention of thrombosis and atherosclerosis. The objective of our study is to design and synthesize potent thromboxane antagonists with prolonged biological half-lives. According to our previous data, potent thromboxane antagonists may contain the following pharmacophores: a sulfonamide, an inter-phenylene ring and a carboxylic acid. These three groups may be concerned with the potency and activity of the antagonists on thromboxane receptors. Antagonist (±)IPA (2-[(3-phenyl- sulfonylaminobicyclo[2.2.1]hept-2-yl)methyl]-phenylpropanoic acid) was synthesized with biological activity. Preliminary studies also show IPA has potent inhibitory action on platelet aggregation.