108655-23-8Relevant articles and documents
Aminothiazoles as γ-secretase modulators
Lübbers, Thomas,Flohr, Alexander,Jolidon, Synese,Jacobsen, Helmut,Ozmen, Laurence,Baumann, Karlheinz,David-Pierson, Pascale
scheme or table, p. 6554 - 6558 (2011/12/04)
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 c-secretase is not inhibited but the formation of the aggregating, toxic Aβ42 peptide is shifted to smaller non-aggregating Ab peptides. Compound 15 reduced brain Abβ42 in vivo in APPSwe transgenic mice at 30 mg/kg p.o.