2. Academic Validation
  3. Aminothiazoles as γ-secretase modulators

Aminothiazoles as γ-secretase modulators

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6554-8. doi: 10.1016/j.bmcl.2011.08.060.
Thomas Lübbers 1,  Alexander Flohr,  Synese Jolidon,  Pascale David-Pierson,  Helmut Jacobsen,  Laurence Ozmen,  Karlheinz Baumann
Affiliations

Affiliation

  • 1 Discovery Chemistry, F. Hoffmann-La Roche Ltd, Grenzacher Strasse 124, 4070 Basel, Switzerland. thomas.luebbers@roche.com
PMID: 21924610 DOI: 10.1016/j.bmcl.2011.08.060
Abstract

We herein report the discovery of a new γ-secretase modulator class with an aminothiazole core starting from a HTS hit (3). Synthesis and SAR of this series are discussed. These novel compounds demonstrate moderate to good in vitro potency in inhibiting amyloid beta (Aβ) peptide production. Overall γ-secretase is not inhibited but the formation of the aggregating, toxic Aβ42 peptide is shifted to smaller non-aggregating Aβ Peptides. Compound 15 reduced brain Aβ42 in vivo in APPSwe transgenic mice at 30mg/kg p.o.

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