【文章名】Design, Synthesis, and Biological Evaluation of Novel Constrained meta-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor a and g Dual Agonists.
Design, Synthesis, and Biological Evaluation of Novel Constrained meta-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor a and g Dual Agonists.
[摘要]：In an effort to develop dual PPARa/g activators with improved therapeutic efficacy, a series of diaryl a-ethoxy propanoic acid compds. comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biol. activities were examd. Most of the compds. possessing an oxime ether linker were more potent PPARg activators than the lead PPARa/g dual agonist, tesaglitazar in vitro. Compd. I, one of the derivs. with an oxime ether linker, was found to selectively transactivate PPARg (EC50 = 0.028 mM) over PPARa (EC50 = 7.22 mM) in vitro and lower blood glucose in db/db mice more than muraglitazar after oral treatment for 11 days.
