Pyridazine-derived gamma-secretase modulators

作者：Wan Zehong^*; Hall Adrian; Jin Yun; Xiang Jia Ning; Yang Eric; Eatherton Andrew; Smith Beverley; Yang Guang; Yu Haihua; Wang Ju; Ye Liang; Lau Lit Fui; Yang Ting; Mitchell William; Cai Wei; Zhang Xiaomin; Sang Yingxia; Wang Yonghui; Tong Zhaolong; Cheng Ziqiang; Hussain Ishrut; Elliott John D; Matsuoka Yasuji

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(13): 4016-4019.

DOI：10.1016/j.bmcl.2011.04.143

• SAR
• gamma-secretase
• Modulator
• AD
• GSI
• GSM
• Pyridazine
• Amyloid-beta

SAR of a novel series of pyridazine-derived gamma-secretase modulators is described. Compound 25 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 the levels of total A beta. Furthermore, 25 demonstrated excellent pharmacokinetic parameters as well as good CNS penetration in the rat.

• 出版日期2011-7-1