7326-74-1Relevant articles and documents
Synthesis,docking and evaluation of phenylacetic acid and trifluoro-methylphenyl substituted benzamide derivatives as potential ppar? agonists
Grewal, Ajmer Singh,Lather, Viney,Pandita, Deepti,Bhayana, Garima
, p. 1239 - 1251 (2017/11/14)
Background: Peroxisome proliferator-activated receptor (PPAR) ? is a type of PPARs belonging to the steroid or nuclear hormone receptor super family. Activation of PPAR? leads to metabolism of fat instead of glucose by body for energy requirements. PPAR? represent an emerging pharmacological target for the treatment of metabolic syndrome (MS). Many selective and potent PPAR? agonists had been synthesized with a potential role in the treatment of various disorders associated with MS including type 2 diabetes and inflammation. Objective: The present work was designed to synthesize and evaluate the antidiabetic and anti-inflammatory activity of some newer phenylacetic acid and trifluoromethylphenyl substituted benzamide derivatives as potential PPAR? agonists. Methods: This work involved the synthesis of newer sulfamoyl benzamide derivatives and their evaluation by molecular docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPAR? protein. Based on the results of the in silico studies, the selected compounds were tested for their antidiabetic and anti-inflammatory activity in the animal models. Results: Amongst the synthesized molecules, compound 7 showed higher anti-diabetic activity and compound 19 showed higher anti-inflammatory activity. The experimental results were found to be in concordance with that of the in silico results. Most of the synthesized molecules were found to have drug like properties as devised by Lipinski's rule of five. Conclusion: These molecules can act as the starting hits for the design of safe, effective and bioavailable PPAR? agonists for the potential treatment of MS and related diseases.
N'-Alkylaminosulfonyl Analogues of 6-Fluorobenzylideneindolinones with Desirable Physicochemical Profiles and Potent Growth Inhibitory Activities on Hepatocellular Carcinoma
Chen, Xiao,Yang, Tianming,Deivasigamani, Amudha,Shanmugam, Muthu K.,Hui, Kam-Man,Sethi, Gautam,Go, Mei-Lin
supporting information, p. 1548 - 1558 (2015/09/07)
The benzylideneindolinone 6-chloro-3-(3′-trifluoromethylbenzylidene)-1,3-dihydroindol-2-one (4) was reported to exhibit potent and selective growth inhibitory effects on hepatocellular carcinoma (HCC). Corroborative evidence supported multi-receptor tyrosine kinase (RTK) inhibition as a possible mode of action. However, the poor physicochemical properties of 4 limited its furtherance as a lead compound. In this study, the modification of 4 was investigated with the aim of improving its potency and physicochemical profile. The 6-fluorobenzylideneindolinone 3-12 bearing a 3′-N-propylaminosulfonyl substituent was found to be a promising substitute. Compound 3-12 [6-fluoro-3-(3′-N-propylaminosulfonylbenzylidene)-1,3-dihydroindol-2-one] was found to be tenfold more soluble than 4 and to have sub-micromolar growth inhibitory activities on HCC cells. It is apoptogenic and inhibits the phosphorylation of several RTKs in HuH7, of which the inhibition of FGFR4 and HER3 are prominent. Compound 3-12 decreased the tumor load in a physiologically relevant orthotopic HCC xenograft murine model. Structure-activity relationships support pivotal roles for the fluoro and N′-propylaminosulfonyl moieties in enhancing cell-based activity and moderating the physicochemical profile (solubility, permeability) of 3-12.
