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 journalArticleResearchpeer-review

8 Citations (Scopus)

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 languageEnglish
Pages (from-to)412-428
JournalEuropean Journal of Medicinal Chemistry
Volume139
DOIs
Publication statusPublished - 20 Oct 2017

Keywords

  • 11β-HSD1 inhibitors
  • Adamantane
  • Aged-related cognitive dysfunction
  • Alzheimer's disease
  • Drug design
  • Glucocorticoids
  • Polycyclic substituents
  • SAMP8 mouse

Fingerprint Dive into the research topics of 'Design, synthesis and in vivo study of novel pyrrolidine-based 11β-HSD1 inhibitors for age-related cognitive dysfunction'. Together they form a unique fingerprint.

Cite this