Carbostyril derivatives having potent beta-adrenergic agonist properties.
Derivatives carrying a substituent in the para position of the phenyl group of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with 15-100-fold lower dissociation constants than that of (-)-isoproterenol. All the above compounds stimulated adenylate cyclase more potently than (-)-isoproterenol. The intrinsic activities of compounds 10 and 12 were equal to that of (-)-isoproterenol. The intrinsic activities of compounds 11 and 13 were 1.3 and 1.2 times that of (-)-isoproterenol, respectively. Treatment of membrane preparations with bromoacetamido derivative 13 resulted in an irreversible loss of binding sites, and thus, 13 seems to be an alkylating affinity label for beta-adrenoceptors.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008566:Membranes / Q000187:drug effects; D015363:Quinolones; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012156:Reticulocytes / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D006912:Hydroxyquinolines; D015363:Quinolones; D011943:Receptors, Adrenergic, beta; C010064:carbostyril; D000262:Adenylyl Cyclases; D007545:Isoproterenol