Structure-activity relationships of novel 3-acylpyrrole derivatives: new inhibitors of platelet aggregation.
Several N-substituted-3-acyl-2, 5-dimethyl pyrrole derivatives were examined for their potency to inhibit aggregation of platelets in vitro and extra vivo in guinea pigs. A structure-activity relationship study showed that the substitution at 3 position of the pyrrole ring affected in vitro activity of inhibiting platelet aggregation. Compounds with 3-benzoyl or 3-thenoyl substituent had greater potency than those with 3-aliphatic acyl substituent. Modification of benzoyl, such as para substitution of phenyl group or reduction of carbonyl group, decreased the activity. There was no clear correlation between that N-substitution of the pyrrole ring and in vitro anti-platelet activity. However, compounds with a longer alkyl chain in the N-substituent had weaker activity. The in vitro inhibitory activity on prostaglandin synthetase of these compounds, though less potent compared with their antiplatelet activity, has a close correlation with the latter. N-substituents of the pyrrole ring had the effect on extra vivo activity. Compounds which have no N-alpha-methyl group and no hetero atoms such as oxygen or sulfur in the N-substituent diminished the extra vivo activity.
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis; D011758:Pyrroles / Q000494:pharmacology*; D012669:Seminal Vesicles / Q000378:metabolism; D013329:Structure-Activity Relationship
D011453:Prostaglandins; D011758:Pyrroles