Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2Y14R antagonists with potential high efficiency against acute gouty arthritis

Author(s):  
Ran Lu ◽  
Yilin Wang ◽  
Chunxiao Liu ◽  
Zhenguo Zhang ◽  
Baiyang Li ◽  
...  
2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Miao Guo ◽  
Xiangtao Kong ◽  
Chunzhi Li ◽  
Qihua Yang

AbstractHydrogenation of benzoic acid (BA) to cyclohexanecarboxylic acid (CCA) has important industrial and academic significance, however, the electron deficient aromatic ring and catalyst poisoning by carboxyl groups make BA hydrogenation a challenging transformation. Herein, we report that Pt/TiO2 is very effective for BA hydrogenation with, to our knowledge, a record TOF of 4490 h−1 at 80 °C and 50 bar H2, one order higher than previously reported results. Pt/TiO2 catalysts with electron-deficient and electron-enriched Pt sites are obtained by modifying the electron transfer direction between Pt and TiO2. Electron-deficient Pt sites interact with BA more strongly than electron-rich Pt sites, helping the dissociated H of the carboxyl group to participate in BA hydrogenation, thus enhancing its activity. The wide substrate scope, including bi- and tri-benzoic acids, further demonstrates the high efficiency of Pt/TiO2 for hydrogenation of BA derivatives.


2020 ◽  
Vol 28 (15) ◽  
pp. 115600
Author(s):  
Thales Kronenberger ◽  
Glaucio Monteiro Ferreira ◽  
Alfredo Danilo Ferreira de Souza ◽  
Soraya da Silva Santos ◽  
Antti Poso ◽  
...  

2019 ◽  
Vol 56 ◽  
pp. 41-48 ◽  
Author(s):  
M. S. Eliseev ◽  
E. L. Nasonov

A significant part of patients with gout has contraindications to taking nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids. Such therapy is often ineffective, particularly in patients with the severe tophaceous gout what hampers treatment of acute arthritis attack assuming the need for other methods of therapy. During the last years several medications have been introduced the mechanism of anti-inflammatory action of which is associated with inhibition of interleukin 1 (IL1) playing a key role in the development of acute gouty arthritis. To date, the most well-studied and the only registered drug for relief of acute arthritis attack is canakinumab, recommended for use in situations where other therapy options are unacceptable. Despite these limitations, the use of IL1 inhibitors, in particular canakinumab, seems promising due to the high efficiency of the drug, the ability to use it in patients with comorbid diseases, as well as a favorable effect on the risk of cardiovascular disease.


2019 ◽  
Author(s):  
K Georgousaki ◽  
N Tsafantakis ◽  
S Gumeni ◽  
V González-Menéndez ◽  
G Lambrinidis ◽  
...  

2019 ◽  
Vol 15 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Samridhi Thakral ◽  
Vikramjeet Singh

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.


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