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Flavones. 2. Synthesis and structure-activity relationship of flavodilol and its analogues, a novel class of antihypertensive agents with catecholamine depleting properties.

Abstract：

:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple flavonoxypropanolamines was prepared to further explore the structural requirements for the antihypertensive effect of these compounds. A structure-activity relationship of these derivatives indicates that the position of the oxypropanolamine side chain, the hydroxy group of the side chain, steric bulkiness and length of N substituents, degree of the N-substitution, phenyl group at the 2-position of the chromone nucleus, and substituents of the phenyl group or B ring of the flavone play significant roles in imparting pharmacological effects. In addition, there is a good correlation between the antihypertensive activity and depletion of myocardial norepinephrine. Of these analogues tested, the most effective one was flavodilol. Only the 8-substituted analogue 6 was found to be a beta-antagonist. Flavodilol was chosen for in-depth pharmacological, toxicological, and clinical evaluation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Wu ES,Cole TE,Davidson TA,Dailey MA,Doring KG,Fedorchuk M,Loch JT 3rd,Thomas TL,Blosser JC,Borrelli AR

doi

10.1021/jm00121a034

subject

Has Abstract,Author List Incomplete

pub_date

1989-01-01 00:00:00

pages

183-92

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

32

pub_type

杂志文章

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