- Discovery of a novel and orally active Farnesoid X receptor agonist for the protection of acetaminophen-induced hepatotoxicity
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Acetaminophen (APAP) overdose is a leading cause of acute hepatic failure and liver transplantation, while the existing treatments are poorly effective. Therefore, it is necessary to develop effective therapeutic drugs for APAP-induced hepatotoxicity. Farnesoid X receptor (FXR) is a potential target for the treatment of liver disease, and the activation of FXR protects mice against APAP-induced hepatotoxicity. Compound 5, a glycine-conjugated derivative of FXR agonist 4, was designed to extend the chemical space of existing FXR agonists. Molecular modeling study indicated that compound 5 formed hydrogen bond network with key residues of FXR. Moreover, compound 5 (10?mg/kg) revealed better protective effects against APAP-induced hepatotoxicity than parent compound 4 (30?mg/kg). Further mechanical research indicated that compound 5 regulated the expressions of genes related to FXR and oxidative stress. These findings suggest that compound 5 is a promising FXR agonist suitable for further research, and it is the first time to verify that the glycine-conjugated derivative five exerted better protective effects than its parent compound.
- Cai, Zongyu,Wang, Bin,Zhou, Zongtao,Zhao, Xin,Hu, Lijun,Ren, Qiang,Deng, Liming,Li, Zheng,Wang, Guangji
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p. 483 - 495
(2021/12/29)
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- Highly efficient heterogeneous V2O5@TiO2 catalyzed the rapid transformation of boronic acids to phenols
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A V2O5@TiO2 catalyzed green and efficient protocol for the hydroxylation of boronic acid into phenol has been developed utilizing environmentally benign oxidant hydrogen peroxide. A wide range of electron-donating and the electron-withdrawing group-containing (hetero)aryl boronic acids were transformed into their corresponding phenol. The methodology was also applied successfully to transform various natural and bioactive molecules like tocopherol, amino acids, cinchonidine, vasicinone, menthol, and pharmaceuticals such as ciprofloxacin, ibuprofen, and paracetamol. The other feature of the methodology includes gram-scale synthetic applicability, recyclability, and short reaction time.
- Upadhyay, Rahul,Singh, Deepak,Maurya, Sushil K.
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supporting information
p. 3925 - 3931
(2021/08/24)
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- SUBSTITUTED ACRYLAMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A pharmaceutical composition comprising a compound having Formula (I) or a pharmacologically acceptable salt thereof as an active ingredient: [wherein, R1 is, for example, a C6-C10 aryl group which may be substituted with one group or more than one group selected from substituent group α; R2 is, for example, a C6-C10 aryl group which may be substituted with one group or more than one group selected from substituent group α; and X is, for example, a hydroxyl group or a C1-C6 alkoxy group].
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