“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

✍ Scribed by Abraham Nudelman; Yitschak Binnes; Naomi Shmueli-Broide; Yael Odessa; J. Paul Hieble; Anthony C. Sulpizio

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 873 KB
• Volume: 329
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19963290304

✦ Synopsis

Vinylogous (Groups IlI and V) and acetylenologous (Group IV) analogs of the classical f3-adrenergic agentsstimulants and blockerswere 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 111, which represent 4-aryl-3-butenyl-2-01-amine analogs of Group 11, retained Pi-adrenoceptor antagonist activity albeit substantially less potent (50-200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group I1 compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists (5a, 5d, 5g), with KB'S ranging from 73-93 nM while 3,4-dichloro substitution (5e) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and Sd, suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the -adrenoceptor confirming the importance of the spatial relationship between the hydroxyf and the amino nitrogen.