'Vinylogs' and 'Acetylenylogs' of β-Adrenergic Agents
| Autor: | Y. Odessa, J. P. Hieble, N. Shmueli‐Broide, Ayelet Nudelman, A. C. Sulpizio, Y. Binnes |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Agonist Vinyl Compounds medicine.drug_class Stereochemistry Adrenergic beta-Antagonists Pharmaceutical Science In Vitro Techniques Chemical synthesis Partial agonist Rats Sprague-Dawley Structure-Activity Relationship Drug Discovery medicine Adrenergic antagonist Animals Potency Acetylene Chemistry Antagonist Biological activity Adrenergic beta-Agonists Atrial Function Myocardial Contraction Rats Aliphatic compound |
| Zdroj: | Archiv der Pharmazie. 329:125-132 |
| ISSN: | 1521-4184 0365-6233 |
| Popis: | Vinylogous (Groups III and V) and acetylenologous (Group IV) analogs of the classical β-adrenergic agents - stimulant and blockers - were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III, which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II, retained β 1 -adrenoceptor antagonist activity albeit substantially less potent (50-200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists (5a, 5d, 5g), with K B 's ranging from 73-93 nM while 3,4-dichloro substitution (5e) markedly reduced antagonist potency (K B = 2,400 nM). Agonist activity was also noted for 5b and 5d, suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β 1 -adrenoceptor confirming the im importance of the spatial relationship between the hydroxyl and the amino nitrogen. |
| Databáze: | OpenAIRE |
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