Synthesis and pharmacological activity of two derivatives of the amide of valproic acid

Valproic acid (VPA), a synthetic branched-chain fatty acid, and its pro-drug the primary amide (VPD) are effective and widely used anti-epileptic agents. Although the use of VPA has grown in recent years, major side effects are still associated with this drug. We presume that it is possible, without loosing the VPD pharmacological profile, to obtain new compounds by undertaking substitutions in the CONH group. N,N'-bis-(2-propylpentanoyl)-1,2-ethanediammine (3) and N,N'-bis-(2-propylpentanoyl)1,3-propanediamine (4) were obtained from VPA (1) using a method reported In the literature. The chemical structures of the new compounds were demonstrated by elemental analysis, IR; and H-1 NMR spectroscopy. Both compounds are less toxic and more effective in protecting the animals from death caused by PTZ than VPD after intraperitoneal administration to mice.