کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1378560 | 982004 | 2005 | 5 صفحه PDF | دانلود رایگان |
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.
α-Fluorosulfones, of general structure 3, were synthesized as an alternative approach to reduce the pKa of the piperidine ring in an existing series of sulfonyl piperidine 5-HT2A antagonists. This work led to the identification of 3b, a selective 5-HT2A antagonist that gave no significant increase in QTc in the anesthetized dog.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 16, 15 August 2005, Pages 3665–3669