Starting from the corresponding acetophenone and glycine derivatives, a series of new 3-aminopyrroles was synthesized in few steps. Using this procedure with hydrazine and hydroxylamine instead of the glycinates provides access to 3-aminopyrazoles and 5-amino 1,2-oxazoles. The various derivatives were tested for anticonvulsant activity in a variety of test models. Several compounds exhibit considerable activity with a remarkable lack of neurotoxicity. 4-(4-Bromophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester, 3, proved to be the most active compound. It was protective in the maximal electroshock seizure (MES) test in rats with an oral ED50 of 2.5 mg/kg with no neurotoxicity noted at doses up to 500 mg/kg. Compound 3 blocks sodium channels in a frequency-dependent manner. The essential structural features which could be responsible for an interaction with an active site of the voltage-dependent sodium channel are established within a suggested pharmacophore model.

New 3‐amino‐ and 5‐aminopyrazoles were synthesised. 3‐Aminopyrazoles exert a strong anticonvulsant effect. 4‐Chlorophenyl‐3‐( morpholin‐4‐yl)‐1H‐pyrazole 2 distinctively blocks sodium channels and is strongly effective in the Maximal Electroshock Seizure (MES) test.

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Synthesis and Anticonvulsant Activity of New 4-Aminopyrazoles and 5-Aminopyrazol-3-ones.-The title pyrazole derivatives (I)-(III), prepared by literature methods, are tested for their anticonvulsant activity. While 4-aminopyrazole derivative (Ia) as well as its p-chlorophenyl analogue possess sodium channel blocking activity, all 5-aminopyrazole derivatives (II) and (III) are inactive due to incorrect distance between endocyclic and exocyclic NH groups. -(LANKAU, H.-J.; MENZER, M.; ROSTOCK, A.; ARNOLD, TH.; RUNDFELDT, CH.; UNVERFERTH, K.; Pharmazie 54 (1999) 9, 705-706;

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