Crystal structure and anticonvulsant activity of (±)-1,2:4,5-di- O-isopropylidene-3,6-di- O-(2-propylpentanoyl)- myo-inositol

Abstract

The biological activity and crystal structure of (±)-1,2:4,5-di- O-isopropylidene-3,6-di- O-(2-propylpentanoyl)- myo-inositol have been investigated. This compound shows better anticonvulsant activity than valproic acid (VPA) in the MES test as measured in mice. Its structure, determined from single-crystal X-ray diffraction measurements, shows that the inositol ring deviates from the ideal chair conformation and that the two 2-propylpentanoyl groups are located on opposite ring positions. This molecular conformation lets carbonyl and hydroxyl oxygen atoms to be available for hydrogen-bonding interactions, hinders carbonyl carbon atoms, preventing metabolic enzymatic hydrolysis, and helps to rationalize the observed inactive profile in the PTZ test. The anticonvulsant activity profile suggests a mechanism different from that of VPA.