Synthesis and Thromboxane A2 antagonist activity of n-benzyltrimetoquinol analogues

Marc W. Harrold, Barbara Grajzl, Yangmee Shin, Karl J. Romstedt, Dennis R. Feller, Duane Miller

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 βadrenergic activity; however, an N-benzyl substituent on TMQ has been shown to impart some selectivity for platelet antiaggregatory activity versus β-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 TXA2PGH2 responses.

Original languageEnglish (US)
Pages (from-to)1506-1512
Number of pages7
JournalJournal of Medicinal Chemistry
Volume31
Issue number8
DOIs
StatePublished - Jul 1 1988
Externally publishedYes

Fingerprint

Tretoquinol
Thromboxane A2
Blood Platelets
Prostaglandin H2 Receptors Thromboxane A2
Adrenergic Agents
Blood Vessels
Prostaglandins
Electrons

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and Thromboxane A2 antagonist activity of n-benzyltrimetoquinol analogues. / Harrold, Marc W.; Grajzl, Barbara; Shin, Yangmee; Romstedt, Karl J.; Feller, Dennis R.; Miller, Duane.

In: Journal of Medicinal Chemistry, Vol. 31, No. 8, 01.07.1988, p. 1506-1512.

Research output: Contribution to journalArticle

Harrold, Marc W. ; Grajzl, Barbara ; Shin, Yangmee ; Romstedt, Karl J. ; Feller, Dennis R. ; Miller, Duane. / Synthesis and Thromboxane A2 antagonist activity of n-benzyltrimetoquinol analogues. In: Journal of Medicinal Chemistry. 1988 ; Vol. 31, No. 8. pp. 1506-1512.
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