Design, synthesis and in vivo study of novel pyrrolidine-based 11β-HSD1 inhibitors for age-related cognitive dysfunction

Rosana Leiva, Christian Griñan-Ferré, Constantí Seira, Elena Valverde, Andrew McBride, Margaret Binnie, Belén Pérez, F Javier Luque, Mercè Pallàs, Axel Bidon-Chanal, Scott P Webster, Santiago Vázquez

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Pages (from-to)412-428
Number of pages17
JournalEuropean Journal of Medicinal Chemistry
Volume139
Early online date4 Aug 2017
DOIs
Publication statusE-pub ahead of print - 4 Aug 2017

Keywords

  • Journal Article

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