Author/Authors :
L. Rebecca Fish، نويسنده , , Myra T. Gilligan، نويسنده , , Alexander C. Humphries، نويسنده , , Magnus Ivarsson، نويسنده , , Tammy Ladduwahetty، نويسنده , , Kevin J. Merchant، نويسنده , , Desmond O’Connor، نويسنده , , Smita Patel، نويسنده , , Elisabeth Philipps، نويسنده , , Hugo M. Vargas، نويسنده , , Peter H. Hutson، نويسنده , , Angus M. MacLeod، نويسنده ,
Abstract :
Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT2A 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 QTc 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-HT2A antagonists in the treatment of insomnia.
