AI Article Synopsis
- - The study focuses on creating new compounds called substituted pyrazolo[1,5-a]quinazolin-5(4H)-ones, which act as negative allosteric modulators for specific receptors (mGlu2 and mGlu3) in the brain.
- - The research builds on previous findings that showed small structural changes in similar compounds can significantly affect their activity on these receptors, encouraging exploration of these new analogues.
- - Among the compounds developed, one particularly effective analogue was identified, showing strong activity against both mGlu2 and mGlu3 receptors while remaining selective and not affecting other types of mGlu receptors.
Article Abstract
Herein we report the design and synthesis of a series of substituted pyrazolo[1,5-a]quinazolin-5(4H)-ones as negative allosteric modulators of metabotropic glutamate receptors 2 and 3 (mGlu2 and mGlu3, respectively). Development of this series was initiated by reports that pyrazolo[1,5-a]quinazoline-derived scaffolds can yield compounds with activity at group II mGlu receptors which are prone to molecular switching following small structural changes. Several potent analogues, including 4-methyl-2-phenyl-8-(pyrimidin-5-yl)pyrazolo[1,5-a]quinazolin-5(4H)-one (10b), were discovered with potent in vitro activity as dual mGlu2/mGlu3 NAMs, with excellent selectivity versus the other mGluRs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075068 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2014.04.051 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!