| Title: | Pyrrolidinones as Modulators of Neurogenesis | ||
| Patent/Patent Application Number: | WO-2015107053-A1 | Publication date: | July 23, 2015 |
| Priority Application: | EP 2013-305365 | Priority date: | January 20, 2014 |
| Inventors: | Jakob-Roetne, R.; Wichmann R.; Peters J.-E.; Jagasia R. | ||
| Assignee Company: | F. Hoffmann La Roche AG, Switzerland | ||
| Disease Area: | Alzheimer’s disease, depression, anxiety disorder, stroke | Therapeutic Target: | Adult neurogenesis for neuroregeneration |
| Summary: | The present application claims a series of pyrrolidinones, imidazolidinones, and hexahydropyrimidinones for the stimulation of neurogenesis from neural stem cells. New functional neurons are generated from adult neural stem cells through the process of adult neurogenesis that occurs throughout life in the adult brain. Extensive evidence suggests that adult hippocampal neurogenesis correlates with cognitive and emotional capacity. The compounds described here are potentially useful in the treatment of a wide range of disorders such as schizophrenia, Alzheimer’s disease, depression, anxiety disorder, stroke, Parkinson’s disease, down syndrome, autism spectrum disorders, traumatic brain injury, and normal aging. | ||
| Important Compound Classes: |  |
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| Definitions: | W is −CH2– or −CH2CH2–. X is CR3R4 or NR5. | ||
| Key Structures: |  |
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| Biological Assay: | The neurogenic properties of the compounds were evaluated based on the proliferation of human embryonic stem cell derived neural stem cells (NSCs). Compounds efficacy is measured by the increase in cells based on ATP levels. The values of EC150 from the dose response curve are determined for each test compound. | ||
| Pharmacological Data: | The EC150 is the compound concentration at which 150% activity of control (100%) is reached.
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| Synthesis: | The synthesis and neurogenic properties of 75 compounds are described. | ||
The authors declare no competing financial interest.