alpha.-Adrenergic agents. 1. Direct-acting .alpha.1 agonists related to methoxamine
| Autor: | J. P. Hieble, D H Shah, Robert M. DeMarinis, Robert G. Pendleton, W. M. Bryan |
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| Rok vydání: | 1981 |
| Předmět: |
Steric effects
Agonist Stereochemistry Chemistry medicine.drug_class Alpha (ethology) In Vitro Techniques Ring (chemistry) Binding Competitive Muscle Smooth Vascular Methoxamine Norepinephrine Adrenergic alpha-Agonists Drug Discovery medicine Animals Molecular Medicine Molecule Amine gas treating Rabbits Phentolamine Muscle Contraction medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 24:1432-1437 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00144a012 |
| Popis: | A series of phenylethylamines related to methoxamine has been prepared and evaluated for direct alpha 1-receptor agonist activity. It has been observed that for open-chain compounds such as methoxamine, in which the amine-containing portion is free to adopt numerous conformations, an hydroxyl group is necessary for direct alpha 1-adrenergic activity. When the hydroxyl is removed, however, the direct component of activity is greatly reduced unless the amine is incorporated into a more sterically defined structure. From our studies we have concluded that in order for a phenylethylamine to be active as a direct alpha 1-receptor agonist it should have a beta nitrogen in a fully extended conformation relative to a substituted phenyl ring. For optimum potency, the nitrogen should be exocyclic to a saturated six-membered ring. It may be further incorporated exocyclic or endocyclic into an additional ring as long as the amine occupies a well-defined region of space relative to the aromatic portion of a molecule. The ED50 values of some of the more potent compounds as alpha 1-receptor agonists are on the order of 1 X 10(-7) M. |
| Databáze: | OpenAIRE |
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