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

R 68070 and CV-4151 are two compounds possessing both thromboxane synt hetase inhibitory activity and thromboxane receptor antagonist propert ies. 2-Heteroaryl 2-substituted phenylketone derivatives with a partia l structural similarity to R 68070 and CV-4151, i.e. possessing a phen yl and a heteroaryl moiety, have been prepared and found to have antip latelet activity. The compound 2-thienyl 2'-hydroxyphenyl ketone (4) w as shown to completely inhibit platelet aggregation induced by arachid onic acid at a concentration of 5.0 mu M. Structure-activity analysis indicated that the presence of a ketone group is an important requirem ent for this inhibitory activity. An o-hydroxyl substitution on the ph enyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitor y activity.