Hsu L Y, Lee C F, Chou T C, Ding Y A
School of Pharmacy, National Defense Medical Center, Taipei, Republic of China.
J Pharm Pharmacol. 1995 Sep;47(9):762-7. doi: 10.1111/j.2042-7158.1995.tb06738.x.
R 68070 and CV-4151 are two compounds possessing both thromboxane synthetase inhibitory activity and thromboxane receptor antagonist properties. 2-Heteroaryl 2-substituted phenylketone derivatives with a partial structural similarity to R 68070 and CV-4151, i.e. possessing a phenyl and a heteroaryl moiety, have been prepared and found to have antiplatelet activity. The compound 2-thienyl 2'-hydroxyphenyl ketone (4) was shown to completely inhibit platelet aggregation induced by arachidonic acid at a concentration of 5.0 microM. Structure-activity analysis indicated that the presence of a ketone group is an important requirement for this inhibitory activity. An o-hydroxyl substitution on the phenyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitory activity.
R 68070和CV - 4151是两种兼具血栓素合成酶抑制活性和血栓素受体拮抗剂特性的化合物。已经制备了与R 68070和CV - 4151具有部分结构相似性的2-杂芳基-2-取代苯乙酮衍生物，即具有苯基和杂芳基部分，并发现它们具有抗血小板活性。化合物2-噻吩基-2'-羟基苯乙酮（4）在浓度为5.0微摩尔时能完全抑制花生四烯酸诱导的血小板聚集。构效关系分析表明，酮基的存在是这种抑制活性的重要条件。苯环上的邻羟基取代以及杂芳基环的2-噻吩基可能会增强抑制活性。
