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Design, synthesis and in vivo study of novel pyrrolidine-based 11β-HSD1 inhibitors for age-related cognitive dysfunction.
European Journal of Medicinal Chemistry 2017 October 21
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.
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