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. 2011 Jul 1;21(13):4016-9.
doi: 10.1016/j.bmcl.2011.04.143. Epub 2011 May 13.

Pyridazine-derived γ-secretase modulators

Zehong Wan  1 , Adrian Hall, Yun Jin, Jia-Ning Xiang, Eric Yang, Andrew Eatherton, Beverley Smith, Guang Yang, Haihua Yu, Ju Wang, Liang Ye, Lit-Fui Lau, Ting Yang, William Mitchell, Wei Cai, Xiaomin Zhang, Yingxia Sang, Yonghui Wang, Zhaolong Tong, Ziqiang Cheng, Ishrut Hussain, John D Elliott, Yasuji Matsuoka
Affiliations

Pyridazine-derived γ-secretase modulators

Zehong Wan et al. Bioorg Med Chem Lett. .

Abstract

SAR of a novel series of pyridazine-derived γ-secretase modulators is described. Compound 25 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain the levels of total Aβ. Furthermore, 25 demonstrated excellent pharmacokinetic parameters as well as good CNS penetration in the rat.

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