title: Initial Optimization of a New Series of γ-Secretase Modulators Derived from a Triterpene Glycoside.
abstract: The discovery of a new series of γ-secretase modulators is disclosed. Starting from a triterpene glycoside γ-secretase modulator that gave a very low brain-to-plasma ratio, initial SAR and optimization involved replacement of a pendant sugar with a series of morpholines. This modification led to two compounds with significantly improved central nervous system (CNS) exposure.
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Nathan O
authors.initials: NO
authors.lastname: Fuller
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Jed L
authors.initials: JL
authors.lastname: Hubbs
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Wesley F
authors.initials: WF
authors.lastname: Austin
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Steffen P
authors.initials: SP
authors.lastname: Creaser
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McKee
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Robyn M B
authors.initials: RM
authors.lastname: Loureiro
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tate
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Weiming
authors.initials: W
authors.lastname: Xia
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ives
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Findeis
authors.affiliation: Satori Pharmaceuticals, Inc. , 281 Albany Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
keywords: Alzheimer’s disease; amyloid β; black cohosh; modulator; γ-secretase