Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines.
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 alpha-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 alpha-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 alpha-adrenoreceptor.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D006634:Histamine H1 Antagonists; D007093:Imidazoles / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D009278:Naphazoline / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013237:Stereoisomerism
D006634:Histamine H1 Antagonists; D007093:Imidazoles; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009278:Naphazoline