4-Fluorosulfonylpiperidines: Selective 5-HT2A ligands for the treatment of insomnia
| Autor: | Hugo M. Vargas, Smita Patel, Kevin John Merchant, Angus Murray Macleod, T. Ladduwahetty, L. Rebecca Fish, Elisabeth Philipps, Magnus Ivarsson, Peter H. Hutson, Myra Gilligan, Desmond O'Connor, Alexander Charles Humphries |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Time Factors Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Ligands Biochemistry Sulfone Structure-Activity Relationship chemistry.chemical_compound Dogs Piperidines Pharmacokinetics Oral administration Sleep Initiation and Maintenance Disorders Internal medicine Drug Discovery medicine Animals Molecular Biology Sulfonyl chemistry.chemical_classification Molecular Structure Organic Chemistry Antagonist Potassium channel Rats Endocrinology chemistry Toxicity Serotonin 5-HT2 Receptor Antagonists Molecular Medicine Piperidine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 15:3665-3669 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2005.05.104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect