Carbamate derivatives of felbamate as potential anticonvulsant agents

摘要

Several monocarbamate compounds derived from felbamate were synthesized and 11 target compounds (1, 4, and 6–14) were initially evaluated in mice MES and PTZ models in our laboratory. Carbamate compounds with varying substituents on the oxygen (1–4) gave anticonvulsant activity with a wide range of ED₅₀ in MES test from 300 mg/kg (4) and compounds with different groups on the nitrogen (5–14) also were quite active in the range of 15 mg/kg (14) to 170.5 mg/kg (6). This suggested that the spatial limitation in the MES model seemed flexible especially on the nitrogen end. All tested compounds showed some activity against mice scPTZ test, but none had the ED₅₀ value <50 mg/kg. Ten selected compounds (1 and 6–14) for subsequent pharmacological evaluation in NIH all gave positive mice MES activity except 8 and 9, which were unexpectedly active in rats after further evaluations. Among the compounds, 1, 8, and 9 advanced to the quantitative study and 1 and 9 provided the highest PI values, 15 and 21, respectively, in the rat oral MES test.