23501-39-5Relevant articles and documents
Design and synthesis of novel quinazolinone-based fibrates as PPARα agonists with antihyperlipidemic activity
Abdallah, Heba M. I.,Abdel-Maksoud, Mohammed S.,Ali, Islam H.,El Kerdawy, Ahmed M.,Ghannam, Iman A. Y.,Hassan, Rasha M.,Sciandra, Francesca
, (2021/12/30)
Aiming to discover new antihyperlipidemic agents, a new set of quinazolinone-fibrate hybrids 9a–r bearing the essential features for peroxisome proliferator-activated receptor-α (PPARα) agonistic activity was synthesized and the structures were confirmed by different spectral data. All the target compounds were screened for their PPARα agonistic activity. Compounds 9o and 9q exhibited potent activity, with EC50 values better than that of fenofibrate by 8.7- and 27-fold, respectively. Molecular docking investigations were performed for all the newly synthesized compounds in the active site of the PPARα receptor to study their interactions and energies in the receptor. Moreover, the antihyperlipidemic and antioxidant activities of compounds 9o and 9q were determined using Triton WR-1339-induced hyperlipidemic rats. Compound 9q exhibited effective hypolipidemic activity in a dose-dependent manner, where it significantly reduced the serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol. Furthermore, it possesses a powerful antioxidant profile where it significantly elevated the levels of reduced glutathione as well as the total antioxidant capacity and significantly decreased the malondialdehyde level. The histopathological studies revealed that compound 9q improved the aortic architecture and hepatic steatosis. These findings support that compound 9q could be a promising lead compound for the development of new antihyperlipidemic agents.
Discovery of novel urea derivatives as dual-target hypoglycemic agents that activate glucokinase and PPARγ
Li, Yongqiang,Tian, Kang,Qin, Aifang,Zhang, Lijian,Huo, Lianchao,Lei, Lei,Shen, Zhufang,Song, Hongrui,Feng, Zhiqiang
, p. 182 - 192 (2014/03/21)
Motivated by the discovery of a potential ligand that activates both glucokinase (GK) and perioxisome proliferator-activated receptor-γ (PPARγ), this work presents the rational design and synthesis of a series of novel urea derivatives as potent dual-targ
FIBRATE COMPOUNDS HAVING PPAR AGONIST ACTIVITY
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Page/Page column 42, (2010/10/20)
There are provided derivatives having PPAR agonist activity. The derivatives include compounds and/or their pharmaceutically acceptable salts; the compounds having the formula (I) wherein A has the structure (II) or (III); X is chosen from -CH2-, -O-, -NH-, and -S-; Y is chosen from -O-, -NH-, and -S-; Z, which may be located in any position of substitution, is hydrogen or halogen; R1 and R2, which may be the same or different, are independently chosen from hydrogen and C1-C8 alkyl, or R1 and R2 together form a carbocyclic ring having from 4 to 6 carbon atoms; R3 is chosen from hydrogen and C1-C8 alkyl; R4, R5, and R6, which may be the same or different, are independently chosen from hydrogen and C1-C8 alkyl; and n is 1 to 6. Various embodiments and variants are provided. In accordance with other aspects, the invention also provides methods of producing a PPARα agonist activity in a mammal, the methods including administering to the mammal an effective amount of certain derivative(s) of the first aspect of the invention, a method of producing a PPARα agonist activity and a PPARα agonist activity in a mammal, the method including administering to the mammal an effective amount of certain derivative(s); and a pharmaceutical composition that includes the derivative(s) of the first aspect of the invention and one or more pharmaceutically-acceptable excipients. Various embodiments and variants are provided.
