VANILLYL-ETHYLAMINE, VANILLYL-METHYLAMINE AND BENZYL-VANILLYLETHYLAMINE; THE RELA- TION OF CHEMICAL STRUCTURE TO PHARMACO- LOGIC ACTION

The intensity of the sympathomi.metic activity of natural and synthetic amines has been shown to increase with the introduc-tion of one and two hydroxyl groups into the benzene nucleus. For instance, Barger and Dale (1910) reported that the magni-tude of the pressor action of tyramine (mono-hydroxy-phenyl-ethylamine) is less than that of catechol-ethylamine (di-hydroxy-phenyl-ethylamine) but greater than that of phenyl-ethylamine. It appeared interesting to consider what would be the effect of blocking one or more of the hydroxyls by conversion into ether groups (methoxy, etc.). Very little research has been done in this direction. Koller (1926) described two ether derivatives of racemic ephedrine: para-methoxy ephedrine and para-hydroxy-meta-methoxy ephedrine, the latter a vanillin derivative. He reported the compounds to have practically no blood pressure effects on animals. Further investigation of ether-amines seemed to be advisable with the view of correlating chemical structure and pharmaco-logic action. Three derivatives of vanillin were selected and prepared especially for this and subsequent studies by methods of Kobayashi (1927) with a modification reported elsewhere (Lange and Hambourger (1931)). These compounds are vanillyl-ethylamine, benzyl-vanillylethylamine, and vanillyl-methyla-mine. No account of their pharmacologic properties has been found in the literature. A comparison of structural formula