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Thiazole-diamides as potent gamma-secretase inhibitors.
Chen, Yuhpyng L; Cherry, Kevin; Corman, Michael L; Ebbinghaus, Charles F; Gamlath, Chandra B; Liston, Dane; Martin, Barbara-Anne; Oborski, Christine E; Sahagan, Barbara G.
Bioorg Med Chem Lett ; 17(20): 5518-22, 2007 Oct 15.
Article in English | MEDLINE | ID: mdl-17764937

ABSTRACT

The thiazole-diamide series (1) has been identified as highly potent gamma-secretase inhibitors. Several representative compounds showed IC(50) values of <0.3 nM. The synthesis and SAR, as well as a radiolabeled synthesis of [(3)H]-2a, are described.


Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Diamide/chemistry , Diamide/pharmacology , Thiazoles/chemistry , Alkylation , Amination , Amyloid Precursor Protein Secretases/metabolism , Cell-Free System , Diamide/chemical synthesis , Magnetic Resonance Spectroscopy , Molecular Structure , Structure-Activity Relationship
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