Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines

Article abstract of DOI:10.1021/jm00234a006

The synthesis of (R) (+) 4 methyl 2 (1 naphthylmethyl)imidazoline hydrochloride (2) and (S) (-) 4 methyl 2 (1 naphthylmethyl)imidazoline hydrochloride (3) is presented. The synthesis involves the preparation of (R) (+) and (S) (-) 1,2 diaminopropane dihydrochloride and then allowing the appropriate diaminopropane to react with ethyl 1 naphthyliminoacetate hydrochloride in the presence of triethylamine. The parent compound, naphazoline, is a potent α adrenoreceptor agonist (-log ED₅₀ = 7.22), whereas the methylated derivatives, 2 and 3, were moderately potent antagonists (pA₂ = 5.6 and 5.8, respectively) of the α adrenoreceptor. Compounds 2 and 3 also produced blockade of the response to histamine on the rabbit aorta, but at concentrations approximately 20 times higher than necessary to produce equal blockade of the α adrenoreceptor.