TY - JOUR
T1 - Design, synthesis and in vivo study of novel pyrrolidine-based 11β-HSD1 inhibitors for age-related cognitive dysfunction
AU - Leiva, R.
AU - Griñan-Ferré, C.
AU - Seira, C.
AU - Valverde, E.
AU - McBride, A.
AU - Binnie, M.
AU - Pérez, B.
AU - Luque, F.J.
AU - Pallàs, M.
AU - Bidon-Chanal, A.
AU - Webster, S.P.
AU - Vázquez, S.
N1 - © 2017 Elsevier Masson SAS
PY - 2017/10/20
Y1 - 2017/10/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85027516297&partnerID=MN8TOARS
U2 - 10.1016/j.ejmech.2017.08.003
DO - 10.1016/j.ejmech.2017.08.003
M3 - Article
SN - 0009-4374
VL - 139
SP - 412
EP - 428
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -