2-HETEROARYL 2-SUBSTITUTED PHENYLKETONE DERIVATIVES AND THEIR INHIBITORY ACTIVITY ON PLATELET-AGGREGATION

• Published in: Journal of pharmacy and pharmacology Vol. 47; no. 9; pp. 762 - 767
• Main Authors: HSU, LY, LEE, CF, CHOU, TC, DING, YA
• Format: Journal Article
• Language: English
• Published: LONDON ROYAL PHARMACEUTICAL SOC GREAT BRITAIN 01.09.1995
• Subjects: Animals; Fatty Acids, Monounsaturated - chemistry; Fatty Acids, Monounsaturated - pharmacology; Fibrinolytic Agents - chemical synthesis; Fibrinolytic Agents - pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Pentanoic Acids - chemistry; Pentanoic Acids - pharmacology; Pharmacology & Pharmacy; Platelet Aggregation Inhibitors - chemical synthesis; Platelet Aggregation Inhibitors - pharmacology; Pyridines - chemistry; Pyridines - pharmacology; Rabbits; Science & Technology; Structure-Activity Relationship; Thromboxane B2 - chemistry; Thromboxane B2 - pharmacology; Thromboxane-A Synthase - antagonists & inhibitors; THROMBOXANE SYNTHASE INHIBITION; PROSTAGLANDIN ENDOPEROXIDES
• ISSN: 0022-3573
• 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 mu M. 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.