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pubmed:abstractText |
A novel series of oxime containing benzyl-1,3-dioxane-r-2-carboxylic acid derivatives (6a-k) were designed as selective PPAR? agonists, through bioisosteric modification in the lipophilic tail region of PPAR?/? dual agonist. Some of the test compounds (6a, 6b, 6c and 6f) showed high selectivity towards PPAR? over PPAR? in vitro. Further, highly potent and selective PPAR? agonist 6c exhibited significant antihyperglycemic and antihyperlipidemic activity in vivo, along with its improved pharmacokinetic profile. Favorable in-silico interaction of 6c with PPAR? binding pocket correlate its in vitro selectivity profile toward PPAR? over PPAR?. Together, these results confirm discovery of novel series of oxime based selective PPAR? agonists for the safe and effective treatment of various metabolic disorders.
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