title: Synthesis and thromboxane A2 antagonist activity of N-benzyltrimetoquinol analogues.
abstract: It is currently believed that the platelet thromboxane A2 (TXA2/PGH2) receptor is different from the vascular TXA2/PGH2 receptor. While the majority of TXA2 receptor antagonists are structurally related to the prostaglandins, trimetoquinol (TMQ) represents a unique nonprostanoid antagonist. TMQ also possesses beta-adrenergic activity; however, an N-benzyl substituent on TMQ has been shown to impart some selectivity for platelet antiaggregatory activity versus beta-adrenergic activity. In this study, we examined the synthesis and TXA2 antagonist activity of a series of substituted N-benzyl analogues of TMQ. While these analogues showed an apparent direct correlation between platelet antiaggregatory activity and electron-donating ability of the N-benzyl substituents, no such correlation could be demonstrated for the inhibition of contractile responses. Thus, nonprostanoid TXA2 antagonists can be used to demonstrate differences between platelet and vascular TXA2/PGH2 responses.
authors.affiliation: Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
authors.forename: M W
authors.initials: MW
authors.lastname: Harrold
authors.forename: B
authors.initials: B
authors.lastname: Grajzl
authors.forename: Y M
authors.initials: YM
authors.lastname: Shin
authors.forename: K J
authors.initials: KJ
authors.lastname: Romstedt
authors.forename: D R
authors.initials: DR
authors.lastname: Feller
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D051381:Rats; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
chemical_list: D007546:Isoquinolines; D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid