Dopamine agonists related to 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol, 6-position modifications
| Autor: | R. G. Franz, Stephen T. Ross, James W. Wilson, Gregory Gallagher, Robert M. DeMarinis, Henry M. Sarau, J. P. Hieble, M. Brenner |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Agonist
Magnetic Resonance Spectroscopy Bicyclic molecule Chemistry medicine.drug_class Stereochemistry Dopamine Diol Biological activity Benzazepines Receptors Dopamine Benzazepine Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Molecular Medicine Potency Indicators and Reagents Rabbits Receptor Adenylyl Cyclases medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 30:35-40 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00384a006 |
| Popis: | The N-allyl derivative (SKF 85174) of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol (SKF 82526) retains the DA-1 agonist potency of the latter compound but unlike the parent also shows substantial DA-2 agonist activity. In a previous study of N-substituted benzazepines these combined agonist effects were shown to be uniquely associated with the N-allyl group. A continuation of this research has examined dependency of combined DA-2/DA-1 agonist activities on 6-position modification with the specific objective of developing an agonist with maximum effectiveness and potency at the DA-2 receptor subtype. DA-2 agonist activity was measured in a rabbit ear artery assay, and DA-1 agonist activity was determined in an adenylate cyclase assay. Replacing chloro with bromo retains the activity pattern and the potency of the chloro compound; replacement with a hydrogen causes a decrease of both DA-1 and DA-2 receptor activating potency. Introduction of a 6-methyl group causes loss of DA-2 agonist activity and reduction in DA-1 agonist potency. Substitution with a 6-fluoro provides the best balance of DA-2 and DA-1 agonist activities; this compound was moderately potent in both assays. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|