3,4-Dihydro-2H-benzo[1,4]oxazine derivatives as 5-HT6 receptor antagonists

A series of novel 3,4-dihydro-2H-benzo[1,4]oxazine derivatives has been designed and synthesized as 5-HT6 receptor antagonists. Many of the compounds displayed subnanomolar affinities for the 5-HT6 receptor and good brain penetration in rats. The relationship of structure and lipophilicity to hERG inhibition of this series of compounds is discussed.

Graphical abstractThe synthesis and structure–activity relationships of a series of 3,4-dihydro-2H-benzo[1,4]oxazine based 5-HT6 antagonists are described.Figure optionsDownload full-size imageDownload as PowerPoint slide