Journal
SCIENCE CHINA-CHEMISTRY
Volume 54, Issue 11, Pages 1688-1701Publisher
SCIENCE PRESS
DOI: 10.1007/s11426-011-4388-6
Keywords
tricyclic sulfones; gamma-secretase; Alzheimer's disease; inhibitors
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Novel tricyclic sulfones as gamma-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues reported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.
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