Synthesis and renal vasodilator activity of 2-chlorodopamine and N-substituted derivatives
| Autor: | Marcia A. Wenger, James R. McCarthy, Mark B. Zimmerman, Lee W. Emmert, Mccowan Jefferson Ray |
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| Rok vydání: | 1986 |
| Předmět: |
Male
Chemical Phenomena Stereochemistry Phenoxybenzamine Dopamine Vasodilation Propranolol Pharmacology Kidney Renal Circulation Structure-Activity Relationship Dogs Drug Discovery medicine Animals Receptor Chemistry Antagonist Biological activity Benzazepines Renal blood flow Molecular Medicine Female medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 29(9) |
| ISSN: | 0022-2623 |
| Popis: | A four-step synthesis of 2-chlorodopamine (2b) is presented as well as methods for the syntheses of the N-methyl, ethyl, and n-propyl analogues (2c-e). Compounds 2b and 2c were essentially equipotent to dopamine for increasing renal blood flow in anesthetized dogs that had been treated with the alpha-adrenergic antagonist phenoxybenzamine. The increases in renal blood flow were blocked by the DA1 antagonist (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine. Compounds 2d and 2e were significantly less potent than dopamine in the same model; the increases in renal blood flow were attenuated by propranolol and blocked by a combination of propranolol and (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine. The significance of an o-chloro substituent on dopamine analogues for the activation of the DA1 receptor is briefly discussed. |
| Databáze: | OpenAIRE |
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