Optically active catecholimidazolines: a study of steric interactions at alpha-adrenoreceptors.
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.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002942:Circular Dichroism; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008968:Molecular Conformation; D009904:Optical Rotation; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014043:Tolazoline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D007202:Indicators and Reagents; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; C038572:2-(3,4-dihydroxybenzyl)imidazoline; C038571:2-(3,4,alpha-trihydroxybenzyl)imidazoline; D014043:Tolazoline; D004837:Epinephrine