In search for new compounds with predictable anticonvulsant properties our attention was drown to a group of 5-cyclopropyl-5-phe- nyl-imidazolidine-2,4-diones with 4-substituted piperazine fragment connected to the N3 nitrogen atom through the methylene linker (N-Mannich bases). In this series, many compounds exhibited potent anticonvulsant activity with an ED₅₀ values ranging from 5.29 mg/kg to 17.06 mg/kg in the MES test and some of them were also active in the sc.PTZ screen with an ED₅₀ ranging from 17.58 mg/kg to 30.78 mg/kg [1].

As a continuation of our research work on structure-activity relationships in the five-member heterocyclic anticonvulsants, we have synthesized series of N-Mannich bases analogues containing 5-cyclopropyl-5-phenyl-imidazolidine-2,4-dione moiety. The main modification was the replacement of a hydrogen atom with an electron-withdrawing chlorine atom at the position-4 of the 5-phenyl ring.

Fig 1.

The target derivatives were prepared by the Mannich-type reaction from the 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-dione, formaldehyde and the appropriately 4-substituted piperazine.

The compounds were evaluated for their anticonvulsant properties within the Antiepileptic Drug Development (ADD) Program, by testing procedures, which have been described earlier [2].

This work was supported by the Polish MNiSW grant No N N405 298536

1. Obniska J., Bytrus H., Czopek A. “Design, synthesis and anticonvulsant activity of N-Mannich bases of 5-cyclopropyl-5-phenyl-hydantoin derivatives” JMMC, 24-27 June 2009 Budapeszt.

2. Kupferberg, H.J. Epilepsia, 30, (suppl.), 51-56, 1989.

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