Design, synthesis and evaluation of novel N -phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy

摘要

KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novelN-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activityin vitroandin vivo. Several compounds were found to be potent KCNQ openers. Compound1with favorablein vitroactivity was submitted to evaluationin vivo. Results showed that compound1owned significant anti-convulsant activity with no adverse effects. It was also found to posses favorable pharmacokinetic profiles in rat. This research may provide novel potent compounds for the discovery of KCNQ openers in treating epilepsy.