Conjugates of Catecholamines. 6. Synthesis and β-Adrenergic Activity of N - (Hydroxyalkyl)catecholamine Derivatives

Publisher Website
Google Scholar
Abstract
A new series of catecholamines was prepared in which the N-alkyl substituent of dl-epinephrine or dl-isoproterenol was extended by a methylene chain terminated by a hydroxyl group or derived functionality (e.g., carbamate or ester). These functionalized catecholamines (congeners) and model compounds were prepared with the goal of eventual attachment to polymeric carrier molecules. The .beta.-adrenergic agonist activity of the derivative was evaluated in vitro by measuring the intracellular accumulation of cAMP in S49 mouse lymphoma cells and by the displacement of iodocyanopindolol (ICYP). A n-butylcarbamate derivative was the most active compound in this series with a potency 190 times greater than dl-isoproterenol in the S49 assay. The biological results indicate that minor modifications in structure in the N-alkyl substituent of the catecholamine can influence the pharmacologic activity.