title: Pyridine-derived γ-secretase modulators.
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.
authors: Research and Development, GlaxoSmithKline Pharmaceuticals, 898 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai 201023, China. Zehong.2.Wan@gsk.com
authors: Zehong
authors: Z
authors: Wan
authors: Adrian
authors: A
authors: Hall
authors: Yingxia
authors: Y
authors: Sang
authors: Jia-Ning
authors: JN
authors: Xiang
authors: Eric
authors: E
authors: Yang
authors: Beverley
authors: B
authors: Smith
authors: David C
authors: DC
authors: Harrison
authors: Guang
authors: G
authors: Yang
authors: Haihua
authors: H
authors: Yu
authors: Helen S
authors: HS
authors: Price
authors: Jian
authors: J
authors: Wang
authors: Julie
authors: J
authors: Hawkins
authors: Lit-Fui
authors: LF
authors: Lau
authors: Matthew R
authors: MR
authors: Johnson
authors: Tina
authors: T
authors: Li
authors: Wei
authors: W
authors: Zhao
authors: William L
authors: WL
authors: Mitchell
authors: Xiaobo
authors: X
authors: Su
authors: Xiaomin
authors: X
authors: Zhang
authors: Yanjiao
authors: Y
authors: Zhou
authors: Yun
authors: Y
authors: Jin
authors: Zhaolong
authors: Z
authors: Tong
authors: Ziqiang
authors: Z
authors: Cheng
authors: Ishrut
authors: I
authors: Hussain
authors: John D
authors: JD
authors: Elliott
authors: Yasuji
authors: Y
authors: Matsuoka
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D011725:Pyridines; D053829:Amyloid Precursor Protein Secretases; C023666:pyridine