Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity was written by Chen, Zhao;Li, Di;Xu, Ning;Fang, Jinzhang;Yu, Yan;Hou, Wei;Ruan, Haoqiang;Zhu, Panpan;Ma, Renchao;Lu, Shiying;Cao, Danhui;Wu, Rui;Ni, Mowei;Zhang, Wei;Su, Weike;Ruan, Benfang Helen. And the article was included in Journal of Medicinal Chemistry in 2019.Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide The following contents are mentioned in the article:
Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, the authors explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogs with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing mols. However, both CB839 and its selenium analogs show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analog of CB839. This study involved multiple reactions and reactants, such as N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide (cas: 1439400-46-0Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide).
N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide (cas: 1439400-46-0) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Application In Synthesis of N-(6-Chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem