Initial optimization of a new series of γ-secretase modulators derived from a triterpene glycoside

Nathan O. Fuller, Jed L. Hubbs, Wesley F. Austin, Steffen P. Creaser, Timothy D. McKee, Robyn M.B. Loureiro, Barbara Tate, Weiming Xia, Jeffrey L. Ives, Mark A. Findeis, Brian S. Bronk

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)908-913
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume3
Issue number11
DOIs
StatePublished - Nov 8 2012

Keywords

  • γ-secretase
  • Alzheimer's disease
  • amyloid β
  • black cohosh
  • modulator

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

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