Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors.
2013
Abstract An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (−)- 1a (SCH 900229), a potent, PS1-selective γ-secretase inhibitor and clinical candidate for the treatment of Alzheimer’s disease. Specifically, 4-CF 3 and 4-Br substituted arylsulfone analogs, (−)- 1b and (−)- 1c , are equipotent to compound (−)- 1a . On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.
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