Pyridine-derived gamma-secretase modulators

作者：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; Zhou Yanjiao; Jin Yun; Tong Zhaolong; Cheng Ziqiang; Hussain Ishrut; Elliott John D; Matsuoka Yasuji

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(16): 4832-4835.

DOI：10.1016/j.bmcl.2011.06.042

• gamma-Secretase inhibitor
• gamma-Secretase modulator
• SAR
• Pyridine

SAR of a novel series of pyridine-derived gamma-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease A beta 42 and A beta 40, and maintain (or increase) the levels of total A beta. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower A beta 42 in the brain without altering Notch processing in the peripheral.

• 出版日期2011-8-15