Biological evaluation of imidazobenzoxazines, imidazobenzoxazin-5-ones and imidazobenzoxazin-5-thiones as sodium channel blockers

摘要

We have evaluated as sodium channel blockers a series of imidazobenzoxazines, imidazobenzoxazin-5-ones and imidazobenzoxazin-5-thiones. We tested these new compounds on NaV1.6 and NaV1.2 sodium channel isoforms, that are expressed in central nervous system and seems to be very important in controlling neuronal firing. Moreover, mutations in SCN2A, the gene encoding NaV1.2, have been identified in patients with generalized epilepsy. Almost all of the new molecules were able to block the NaV1.6 sodium currents and some of them displayed IC50 values in the low micromolar range.