Bioorganic and Medicinal Chemistry Letters p. 4212 - 4216 (2005)
Update date:2022-07-29
Topics:
Sparey, Tim
Beher, Dirk
Best, Jonathan
Biba, Mirlinda
Castro, Jose L.
Clarke, Earl
Hannam, Joanne
Harrison, Timothy
Lewis, Huw
Madin, Andrew
Shearman, Mark
Sohal, Bindi
Tsou, Nancy
Welch, Christopher
Wrigley, Jonathan
A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl- substituted cyclic sulfamides with good in vitro and in vivo γ-secretase activity. One compound with subnanomolar activity elicited a reduction in brain Aβ40 after oral dosing in APP-YAC mice.
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