Synthesis and Anti-histaminic Evaluation of N-Phenyl-(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines

Abstract

New N-phenyl(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines, 5a -e, have been synthesized from the corresponding 3-phenyl(alkyl)carbamoyl-2-iminooxazolidines 2. A two-stage hydrolysis reaction led finally to the corresponding ring-opened N-phenyl(alkyl)-N 0 -[1-{3-(dialkylamino)-propan-2-ol}]ureas 4. The oxazoline ring was regenerated through an intramolecular nucleophilic substitution involving an halogen atom introduced by the reaction of thionyl chloride on 4. Pharmacological properties of 5a -e were evaluated on histaminic and adrenergic receptors in guinea-pig trachea and rat aorta. Compounds 5b and 5e showed a selective anti-histaminic effect on guinea-pig airways, but a significant response was obtained for a concentration > 10 26 M. No pharmacological activity was obtained with oxazoline 5c whereas oxazolines 5a and 5d seemed to present a non-selective effect on the contractile mechanism of the smooth muscle cell.