AI Article Synopsis
- - A new series of compounds (6a-k) were developed as selective PPARα agonists by modifying the lipophilic tail region of existing dual agonists.
- - Some of these compounds (6a, 6b, 6c, and 6f) showed strong selectivity for PPARα over PPARγ in lab tests, with compound 6c demonstrating impressive antihyperglycemic and antihyperlipidemic effects in live models.
- - The favorable interaction of compound 6c with the PPARα binding pocket supports its selectivity and effectiveness, indicating potential for treating metabolic disorders safely and effectively.
Article Abstract
A novel series of oxime containing benzyl-1,3-dioxane-r-2-carboxylic acid derivatives (6a-k) were designed as selective PPARα agonists, through bioisosteric modification in the lipophilic tail region of PPARα/γ dual agonist. Some of the test compounds (6a, 6b, 6c and 6f) showed high selectivity towards PPARα over PPARγ in vitro. Further, highly potent and selective PPARα agonist 6c exhibited significant antihyperglycemic and antihyperlipidemic activity in vivo, along with its improved pharmacokinetic profile. Favorable in-silico interaction of 6c with PPARα binding pocket correlate its in vitro selectivity profile toward PPARα over PPARγ. Together, these results confirm discovery of novel series of oxime based selective PPARα agonists for the safe and effective treatment of various metabolic disorders.
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| http://dx.doi.org/10.1016/j.bmcl.2010.12.032 | DOI Listing |
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