CARBAMATE DERIVATIVES RELATED TO MEPROBAMATE

A series of 2-substituted 1,3-propanediol dicarbamates, related chemically to meprobamate, has been prepared for central nervous system pharmacological investigation. The N-unsubstituted propanediol dicarbamates were obtained by an ester-exchange reaction between the corresponding diol and urethan, by phosgenation of the diol followed by ammoniation of the bis(chlorocarbonate) derivative, by the reaction of the diol with cyanic acid, and by ammoniation of the bis(phenylcarbonate) derivative of the appropriate diol. The symmetrically N,N′-substituted propanediol dicarbamates were synthesized by direct carbamoylation of the propanediols, and the unsymmetrically substituted derivatives by stepwise carbamoylation via the m-dioxanone and hydroxypropyl carbamate intermediates using similar carbamoylation reactions. In addition to the preparation and physical properties of these compounds, the muscle paralyzing activity, anticonvulsant activity, and toxicity of these carbamates and many of the intermediates employed in their synthesis are presented. Structure-activity relationships among these compounds are discussed. © 1969, American Chemical Society. All rights reserved.