Syntheses and Pharmacological Activities of 2-(Substituted Phenoxymethyl) morpholine Derivatives

Abstract

Seventeen 2-(substituted phenoxymethyl) morpholines were synthesized by the reduction of 6-(substituted phenoxymethyl)morpholin-3-one or by the reaction of 1,2-epoxy-3-(substituted phenoxy) propane, 2-aminoethyl hydrogen sulfate and sodium hydroxide in a mixture of water and ethanol. These compounds were tested for effectiveness in preventing reserpine-induced ptosis and in prolonging the survival time of mice subjected to hypobaric hypoxia.In the reserpine ptosis test, o-benzyl, o-(3-thenyl), o-(2-pyridylmethyl) and o-(2-thenyl) substituted 2-phenoxymethylmorpholine (VIn, VIl, VIe and VIh) were effective with RD30 values of 3, 9, 10 and 12 mg/kg (p.a.), respectively.In the antihypoxia test, p-(2-thenyl), o-(5-methyl-2-thenyl) and m-(2-thenyl)substituted 2-phenoxymethylmorpholine (VIj, VIk and VIi) and VIh were effective with survival times of 515.0, 375.8, 346.7 and 406.7 s, respectively.From these results the two most promising compounds, VIh and VIn were tested for amelioration of CO2-induced amnesia. VIn but not VIn showed ameliorative activity.