Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARalpha selective activators.
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Li Z, Liao C, Ko BC, Shan S, Tong EH, Yin Z, Pan D, Wong VK, Shi L, Ning ZQ, Hu W, Zhou J, Chung SS, Lu XP
Design, synthesis, and evaluation of a new class of noncyclic 1,3-dicarbonyl compounds as PPARalpha selective activators.
Bioorg Med Chem Lett. 2004 Jul 5;14(13):3507-11.
- PubMed ID
- 15177462 [ View in PubMed]
- Abstract
Lipid accumulation in nonadipose tissues is increasingly linked to the development of type 2 diabetes in obese individuals. We report here the design, synthesis, and evaluation of a series of novel PPARalpha selective activators containing 1,3-dicarbonyl moieties. Structure-activity relationship studies led to the identification of PPARalpha selective activators (compounds 10, 14, 17, 18, and 21) with stronger potency and efficacy to activate PPARalpha over PPARgamma and PPARdelta. Experiments in vivo showed that compounds 10, 14, and 17 had blood glucose lowering effect in diabetic db/db mouse model after two weeks oral dosing. The data strongly support further testing of these lead compounds in other relevant disease animal models to evaluate their potential therapeutic benefits.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rosiglitazone Peroxisome proliferator-activated receptor alpha EC 50 (nM) 140 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor delta EC 50 (nM) 3620 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma EC 50 (nM) 2880 N/A N/A Details