The synthesis, reactivity, and pharmacological properties of some substituted NN -dimethyl-2-halogeno-2-phenylethylamines, and related compounds

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Abstract
With the object of clarifying ideas about the epinephrine a-receptor and antagonism to catecholamines, a series of compounds mentioned in the title, with 3-,4-, or 3,4-substituents in the phenyl group, was synthesized; the compounds were isolated as their hydrohalides and subjected to both physicochemical and pharmacological investigations. The epinephrine, anti-norepinephrine, and anti-histamine activities of many of the compounds are reported. Differences in properties of this class of halogenoethylamines from those previously observed of the many members of the "Dibenamine" (NN-dibenzyl-2-chloroethylamine hydrochloride) class are confirmed. Structure-activity relationships for the anti-adrenaline compounds are fully discussed Belleau''s theory of the epinephrine [alpha]-receptor (Belleau 1958), successful as it is in explaining the behavior of the "Dibenamine" group, is not fully adequate to explain the behavior of the present compounds. A development of the theory is proposed in which the importance of similar geometry for agonist and antagonist, and of the site in the receptor binding the alcoholic hydroxyl group of the agonist is emphasized. The anti-histamine properties of some of the compounds are briefly considered.