1. Pyridine-derived γ-secretase modulators
- Author
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Wan, Zehong, Hall, Adrian, Sang, Yingxia, Xiang, Jia-Ning, Yang, Eric, Smith, Beverley, Harrison, David C., Yang, Guang, Yu, Haihua, Price, Helen S., Wang, Jian, Hawkins, Julie, Lau, Lit-Fui, Johnson, Matthew R., Li, Tina, Zhao, Wei, Mitchell, William L., Su, Xiaobo, Zhang, Xiaomin, and Zhou, Yanjiao
- Subjects
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ENZYME inhibitors , *PYRIDINE , *STRUCTURE-activity relationship in pharmacology , *HETEROCYCLIC compounds , *PHARMACEUTICAL chemistry , *BRAIN physiology , *THERAPEUTICS - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2011
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