Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-containing pyrazolo[3,4-b]pyridinones as a new series of AMPKα1β1γ1 activators was written by Xiao, Zhihong;Peng, Yajun;Zheng, Bifeng;Chang, Qi;Guo, Yating;Chen, Zhuo;Li, Qianbin;Hu, Gaoyun. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2021.Name: 2-(Trifluoromethoxy)benzonitrile This article mentions the following:
Three series of 1,2,4-oxadiazole-containing pyrazolo[3,4-b]pyridinone derivatives I [R1 = 2-Me, 3-OMe, 4-F, etc.; R2 = CF3, COOH; R3 = H, 4-methoxybenzyl; R4 = H, 4-methoxybenzyl] were synthesized and reported as AMPKα1β1γ1 activators. The in vitro biol. assay demonstrated that compounds I [R1 = 4-Cl; R2 = CF3; R3 = H; R4 = H] (EC50[AMPKα1γ1β1] = 180 nM) and I [R1 = 3-CF3; R2 = COOH; R3 = H; R4 = H] (EC50[AMPKα1γ1β1] = 2 nM) displayed significant enzyme activation. Mechanism studies indicated that both compounds reduced the levels of reactive oxygen species in a rat kidney fibroblast cell line (NRK-49F) stimulated by transforming growth factor-β and induced early apoptosis of NRK-49F cells at 10μM. Mol. docking studies suggested that compoundI [R1 = 3-CF3; R2 = COOH; R3 = H; R4 = H] exhibited critical hydrogen-bond interactions with the critical amino acid residues Lys29, Lys31, Asn111, and Asp88 at the binding site of the AMPK protein. These results enriched the structure pool of AMPK activators and provided novel lead compounds for the subsequent development of compounds with a promising therapeutic potential against DN. In the experiment, the researchers used many compounds, for example, 2-(Trifluoromethoxy)benzonitrile (cas: 63968-85-4Name: 2-(Trifluoromethoxy)benzonitrile).
2-(Trifluoromethoxy)benzonitrile (cas: 63968-85-4) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Name: 2-(Trifluoromethoxy)benzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts