Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370132 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Abstract
Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain Aβ42 levels in mice and rats.
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Related Topics
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Organic Chemistry
Authors
Zhili Xin, Hairuo Peng, Andrew Zhang, Tina Talreja, Gnanasambandam Kumaravel, Lin Xu, Ellen Rohde, Mi-yong Jung, Melanie N. Shackett, David Kocisko, Sowmya Chollate, Anthone W. Dunah, Pamela A. Snodgrass-Belt, H. Moore Arnold, Arthur G. Taveras,