4-Fluorosulfonylpiperidines: selective 5-HT2A ligands for the treatment of insomnia.

Abstract Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT 2A antagonists gave compounds with increased selectivity over the IKr potassium channel. This work led to the identification of 3b , a compound that gave no increase in QT c in the anesthetized dog up to plasma levels as high as 148 μM. Furthermore, 3b has been shown to increase slow-wave sleep bout duration and to decrease the number of awakenings in rats, indicating the potential utility of 5-HT 2A antagonists in the treatment of insomnia.