Abstract
© 2017 Elsevier Masson SAS Recent findings suggest that treatment with 11β-HSD1 inhibitors provides a novel approach to deal with age-related cognitive dysfunctions, including Alzheimer's disease. In this work we report potent 11β-HSD1 inhibitors featuring unexplored pyrrolidine-based polycyclic substituents. A selected candidate administered to 12-month-old SAMP8 mice for four weeks prevented memory deficits and displayed a neuroprotective action. This is the first time that 11β-HSD1 inhibitors have been studied in this broadly-used mouse model of accelerated senescence and late-onset Alzheimer's disease.
Original language | English |
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Pages (from-to) | 412-428 |
Journal | European Journal of Medicinal Chemistry |
Volume | 139 |
DOIs | |
Publication status | Published - 20 Oct 2017 |
Keywords
- 11β-HSD1 inhibitors
- Adamantane
- Aged-related cognitive dysfunction
- Alzheimer's disease
- Drug design
- Glucocorticoids
- Polycyclic substituents
- SAMP8 mouse