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ABSTRACT: SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain (or increase) the levels of total Aβ. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aβ42 in the brain without altering Notch processing in the peripheral.
Bioorganic & medicinal chemistry letters 08/2011; 21(16):4832-5. DOI:10.1016/j.bmcl.2011.06.042 · 2.33 Impact Factor