AI Article Synopsis
- Efforts continued to find alternative compounds for the selective PPARγ modulator DS-6930 by replacing its 2-pyridine ring with 3- or 4-pyridyl groups.
- Modifying the pyridine ring didn't lead to strong partial agonists, prompting researchers to investigate changes to the benzimidazole ring for potential intermediate agonists.
- Among various modifications, the 7'-fluoro benzimidazole (DS19161384) showed promising results, significantly lowering plasma glucose levels while exhibiting good pharmacokinetic properties.
Article Abstract
Derivatization efforts were continued to discover backups for a potent selective PPARγ modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modifications of benzimidazole ring were explored to discover potent intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed to show potent efficacy in vivo, whereas 7'-fluoro benzimidazole (DS19161384) was found to result in robust plasma glucose reductions with excellent DMPK profiles.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421586 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.8b00645 | DOI Listing |
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