©　2018,　Springer　Science+Business　Media,　LLC,　part　of　Springer　Nature.　In　this　article,　a　novel　series　of　(E)-3-(3,4,5-trimethoxyphenyl)acrylic　acid　(TMCA)　amide　derivatives　1-18　were　designed　and　synthesized　by　a　facile　and　one-pot　step,　which　were　achieved　with　good　yields　using　1-hydroxybenzotriazole　(HOBT)　and　1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide　hydrochloride　(EDCI)　as　activation　system.　All　the　synthesized　derivatives　were　biologically　evaluated　for　their　anticonvulsant,　sedative　activity　and　neurotoxicity　using　the　maximal　electroshock　(MES)　model,　sc-pentylenetetrazol　(PTZ)　model,　pentobarbital　sodium-induced　sleeping　model,　and　locomotor　activity　tests,　respectively.　Among　them,　compounds　4,　9　and　16　exhibited　good　anticonvulsant　activity　in　primary　evaluation.　Furthermore,　compound　4　is　the　most　effective　anticonvulsant　and　sedative　agent　in　subsequent　tests,　while　the　low　threshold　of　toxicity　of　compound　4　is　vigilant.　Compounds　9　and　16　also　performed　significantly　anticonvulsant　activity　in　subsequent　tests　with　weak　toxicity.　The　molecular　modeling　experiments　also　predicted　good　binding　interactions　of　the　obtained　active　molecules　with　the　GABA　transferas.　Therefore,　it　could　be　concluded　that　the　synthesized　derivatives　4,　9　and　16　would　represent　useful　lead　compounds　for　further　investigation　in　the　development　of　anticonvulsant　and　sedative　agents.