Design and structural analysis of novel pharmacophores for potent and selective peroxisome proliferator-activated receptor gamma agonists.
نویسندگان
چکیده
Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.
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عنوان ژورنال:
- Journal of medicinal chemistry
دوره 52 8 شماره
صفحات -
تاریخ انتشار 2009