title: Prodrugs of etilefrine: synthesis and evaluation of 3'-(O-acyl) derivatives.
abstract: A series of 3'-(O-acyl) derivatives of etilefrine (alpha-[(ethylamino)methyl]-3'-hydroxybenzyl alcohol) was synthesized. Correlations between structure and solubility, pKa value, lipophilicity, and esterase-catalyzed hydrolysis were demonstrated. Of special interest is the 3'-(O-pivaloyl) derivative, which shows, in addition to favorable solubility and improved lipophilicity, marked stability against enzymatic cleavage in blood along with a high rate of hydrolysis in the liver.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005039:Etilefrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D010656:Phenylephrine / Q000031:analogs & derivatives*; D051381:Rats; D012995:Solubility
chemical_list: D010656:Phenylephrine; D005039:Etilefrine