Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines.

TitleStereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines.
Publication TypeJournal Article
Year of Publication1976
AuthorsMiller DD, Hsu FL, Ruffolo RR, Patil PN
JournalJ Med Chem
Volume19
Issue12
Pagination1382-4
Date Published1976 Dec
ISSN0022-2623
KeywordsAnimals, Aorta, Histamine H1 Antagonists, Imidazoles, In Vitro Techniques, Muscle, Smooth, Naphazoline, Phenylephrine, Rabbits, Receptors, Adrenergic, Receptors, Adrenergic, alpha, Stereoisomerism
Abstract

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.

Alternate JournalJ. Med. Chem.
PubMed ID12368