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Aminothiazoles as γ-secretase modulators.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lübbers T,Flohr A,Jolidon S,David-Pierson P,Jacobsen H,Ozmen L,Baumann K

doi

10.1016/j.bmcl.2011.08.060

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

6554-8

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01155-3

journal_volume

21

pub_type

杂志文章

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