Optically active catecholimidazolines: a study of steric interactions at .alpha.-adrenoreceptors

• Published in: Journal of medicinal chemistry Vol. 26; no. 7; pp. 957 - 963
• Main Authors: Miller, Duane D, Hamada, Akihiko, Craig, Edward C, Christoph, Gary G, Galluci, Judith C, Rice, Peter J, Banning, Jon W, Patil, Popat N
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.07.1983
• Subjects: Animals; Aorta - metabolism; Circular Dichroism; Epinephrine - pharmacology; In Vitro Techniques; Indicators and Reagents; Kinetics; Molecular Conformation; Optical Rotation; Rats; Receptors, Adrenergic - drug effects; Receptors, Adrenergic, alpha - drug effects; Stereoisomerism; Structure-Activity Relationship; Tolazoline - analogs & derivatives; Tolazoline - chemical synthesis; Tolazoline - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00361a005

The optical isomers and deoxy form of 2-(3,4, alpha-trihydroxybenzyl)imidazoline hydrochloride were examined for their alpha-adrenergic activity on rat aorta. The rank order of stimulant activity was deoxy (2) congruent to (R)-(-)-1 greater than (S)-(+)-1. This is in contrast to catecholamines in which the order of activity is (R)-(-)-epinephrine greater than (S)-(+)-epinephrine = epinine (deoxyepinephrine). The relative order of potency for the isomers of 2-(3,4, alpha-trihydroxybenzyl)imidazoline is different than that predicted by the Easson--Stedman theory for stereoisomers of catecholamines. Also, substitution of the deoxy compound 2 with substituents, methyl or benzyl, in the 4-position lowers the alpha-adrenergic agonist activity, and differences observed between optical isomers were small.