Document Detail

Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach.
MedLine Citation:
PMID:  22061640     Owner:  NLM     Status:  Publisher    
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.
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; Kenneth J Rhodes; Robert H Scannevin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-19
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  -     ISSN:  1464-3405     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Department of Medicinal Chemistry, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Discovery, optimisation and in vivo evaluation of novel GPR119 agonists.
Next Document:  The discovery of novel cyclohexylamide CCR2 antagonists.