N-SEC- AND N-T-ALKYL DERIVATIVES OF METHOXAMINE AND RELATED COMPOUNDS

A number of N-sec- and N-t-alkyl derivatives derived from or relatedto methoxamine [erythro-α-(2,5-dimethoxyphenyl)-β-aminopropanol] have been prepared. Some of these compounds exhibited the physiological properties of “β-blockers” and antiarrhythmic agents. Several hada marked tendency to lower the blood levels of glucose and free fatty acids. In vivo N-sec-alkyl compounds were found to be degraded metabolically to the parent methoxamine (among other products) but the N-t-alkyl system was stable as regards this degradation. The sec-alkyl derivatives were prepared mainly by reductive alkylation of methoxamine, t-alkyl compounds from the appropriate amine and bromo ketone followed by reduction. When reductive alkylation created a third point of asymmetry, the physiologically inferior enantiomeric pair D-alkylamino-(-)-methoxamine-L-alkylamino-(+)-methoxamine was formed preferentially. Some conclusions are possible as to the spatial requirements of “receptor” sites. © 1968, American Chemical Society. All rights reserved.