Pyridopyridazine antagonists of the hedgehog signaling pathway are described. Designed to optimize our previously described phthalazine smoothened antagonists, a representative compound eliminates a PXR liability while retaining potency and in vitro metabolic stability. Moreover, the compound has improved efficacy in a hedgehog/smoothened signaling mouse pharmacodynamic model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2010.06.006 | DOI Listing |
Publication Analysis
Top Keywords
addressing pxr
4
pxr liabilities
4
liabilities phthalazine-based
4
phthalazine-based hedgehog/smoothened
4
hedgehog/smoothened antagonists
4
antagonists novel
4
novel pyridopyridazines
4
pyridopyridazines pyridopyridazine
4
pyridopyridazine antagonists
4
antagonists hedgehog
4
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!