Synthesis of Dibenzofuranone-Oxime Derivatives with Anticonvulsant, Antihypoxic, and Anti-Ischemic Activity

Abstract

New dibenzofuranone-oxime derivatives were designed based on active structures of oxime esters. Compounds of the proposed group were synthesized using 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-one oxime and aromatic acid chlorides. The anticonvulsant activity of the new compounds was studied. The structure— activity relationship was analyzed. Compound 1a [3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1(2H)-one O-(3,4-dichlorobenzoyl)oxime] was the most active compound after i.p. injection to mice in the maximal electroshock test over a wide dose range of 20 – 100 mg/kg. Compound 1a at doses of 10 and 30 mg/kg exhibited antihypoxic activity in a hypoxia test with hypercapnia in a hermetic chamber and anti-ischemic activity at a dose of 10 mg/kg in a rat ischemic stroke model.