Research and Development, GlaxoSmithKline Pharmaceuticals, 898 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai 201023, China.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4832-5. doi: 10.1016/j.bmcl.2011.06.042. Epub 2011 Jun 17.
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.
描述了一系列新型吡啶衍生γ-分泌酶调节剂的 SAR。发现化合物 5 是一种有效的体外调节剂，进一步研究发现，它可以降低 Aβ42 和 Aβ40，同时维持（或增加）总 Aβ 的水平。此外，代表性化合物 1 和 5 体内实验证明可以降低大脑中的 Aβ42，而不改变外周 Notch 的处理。
