Flavones. 2. Synthesis and structure-activity relationship of flavodilol and its analogs. A novel class of antihypertensive agents with catecholamine depleting properties
| Autor: | M. A. Dailey, T. L. Thomas, T. A. Davidson, T. E. Cole, A. R. Borrelli, M. Fedorchuk, E. S. C. Wu, James C. Blosser, K. G. Doring, J T Loch rd |
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| Rok vydání: | 1989 |
| Předmět: |
Male
Steric effects Chemical Phenomena Stereochemistry Flavones Propanolamines Structure-Activity Relationship chemistry.chemical_compound Catecholamines Rats Inbred SHR Adrenal Glands Drug Discovery Side chain medicine Animals Phenyl group Structure–activity relationship Antihypertensive Agents Chromatography High Pressure Liquid Brain Chemistry Flavonoids chemistry.chemical_classification Myocardium Heart Rats Chemistry chemistry Chromone Catecholamine Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 32:183-192 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00121a034 |
| Popis: | (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. |
| Databáze: | OpenAIRE |
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