Document Detail


Optimization of a Natural Product-Based Class of Gamma Secretase Modulators.
MedLine Citation:
PMID:  23030762     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A series of triterpene-based gamma-secretase modulators is optimized. An acetate present at the C24 position of the natural product was replaced with either carbamates or ethers to provide compounds with better metabolic stability. With one of those pharmacophores in place at C24, morpholines or carbamates were installed at the C3 position to refine the physicochemical properties of the analogs. This strategy gave compounds with low clearance and good distribution into the central nervous system (CNS) of CD-1 mice. Two of these compounds, 100 and 120 were tested for a pharmacodynamic effect in the strain and lowered brain Aβ42 levels.
Authors:
Jed L Hubbs; Nathan O Fuller; Wesley F Austin; Ruichao Shen; Steffen P Creaser; Timothy D McKee; Robyn M B Lourerio; Barbara Tate; Weiming Xia; Jeffrey L Ives; Brian S Bronk
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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