Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach

…, S Chollate, AW Dunah, PA Snodgrass-Belt…

文献索引：Xin, Zhili; Peng, Hairuo; Zhang, Andrew; Talreja, Tina; Kumaravel, Gnanasambandam; Xu, Lin; Rohde, Ellen; Jung, Mi-Yong; Shackett, Melanie N.; Kocisko, David; Chollate, Sowmya; Dunah, Anthone W.; Snodgrass-Belt, Pamela A.; Moore Arnold; Taveras, Arthur G.; Rhodes, Kenneth J.; Scannevin, Robert H. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 24 p. 7277 - 7280

全文：HTML全文

被引用次数: 11

摘要

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 ...