| Title: | Novel Benzoisoxazole as Partial Agonist of the 5-HT4 Receptor | ||
| Patent/Patent Application Number: | WO 2011/101774 A1 | Publication date: | August 25, 2011 |
| Priority Application: | US 2010-304921P | Priority date: | February 26, 2010 |
| Inventors: | Noguchi, H.; Waizumi, N. | ||
| Assignee Company: | Pfizer Inc., USA | ||
| Disease Area: | Neurodegenerative disease or disorder | Biological Target: | 5-HT4 receptor |
| Summary: | This application claims a single compound, the serotonin 5-HT4 receptor partial agonist (R)-4-((4-((4-(tetrahydrofuran-3-yloxy)benzo[d]isoxazol-3-yloxy)methyl)piperidin-1-yl)methyl)tetrahydro-2 H-pyran-4-ol, as potential treatment for neurodegenerative diseases and disorders such as Alzheimer’s disease, dementia, depression, schizophrenia, anxiety, mood disorders, and attention deficit/hyperactivity disorder. | ||
| Key Structures: |  |
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| Recent Review Articles: | 1. Ahmad I.; Nirogi R.. 5-HT4 receptor agonists for the treatment of Alzheimer's disease. Neurosci. Med. 2011, 2 (2), 87−92. | ||
| 2. Modica M. N.; Pittala V.; Romeo G.; Salerno L.; Siracusa M. A.. Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years. Curr. Med. Chem. 2010, 17 (4), 334−362. | |||
| Biological Assay: | Agonist-induced cAMP elevation in human 5-HT4d transfected HEK293. Intrinsic activity (IA) is reported as percent agonist effect. THLE assay to predict cell health and measure cell depletion. Human Liver microsome (HLM) stability assay. Clearance is expressed as an extraction ratio (Er), which is calculated as hepatic clearance/hepatic blood flow. | ||
| Biological Data: |  |
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| Synthesis: | Two different synthetic routes are described. Route 1 is for kiloscale synthesis. | ||
| Claims: | Claims 4−7: Use of compounds for the treatment of neurodegenerative diseases and disorders. | ||
Author Present Address
† Present Address: Adjunct Associate Professor, Department of Pharmacology and Physiology, Drexel University, College of Medicine, New College Building, 245 N. 15th Street, Philadelphia, PA 19102.
The authors declare no competing financial interest.