14910-06-6Relevant articles and documents
Synthesis, biological evaluation, and molecular modeling studies of acetophenones-tethered 1,2,4-triazoles and their oximes as epidermal growth factor receptor inhibitors
Abdel-Rahman, Hamdy M.,Ali, Ahmed M.,El-Wahab, Hend A. A. Abd,Qayed, Wesam S.
, (2021/11/27)
A series of 5-(4-pyridyl)-1,2,4-triazoles hybrids with acetophenones and their oxime derivatives was rationally designed and synthesized as epidermal growth factor receptor (EGFR) kinase inhibitors. Initially, drug Likeness and pharmacokinetics properties of the prepared compounds were evaluated. Afterward, the prepared compounds were in vitro screened for their ability to inhibit the growth of the NCI-60 human cancer cell lines where certain compounds showed moderate activity. Compounds 4e and 5b emerged as the most potent compounds in this series were further tested for their EGFR enzyme inhibition activity. They showed IC50 values of 0.14 and 0.18?μM, respectively, in comparison with Gefitinib as a reference with an IC50 value of 0.06?μM. Docking of compounds 4e and 5b into the binding site of EGFR tyrosine kinase was performed to explains their possible binding mode and to compare it with known inhibitors. Moreover, molecular dynamic simulations were estimated for deeper understanding of the binding mode of compounds 4e and 5b at the binding site of EGFR tyrosine kinase. The findings indicated that the novel ligands 4e and 5b were stable in the EGFR tyrosine kinase active site.
Heterocycles 39. Synthesis, characterization and evaluation of the anti-inflammatory activity of thiazolo[3,2-b][1,2,4]triazole derivatives bearing pyridin-3/4-yl moiety
Toma, Alexandra,Mogo?an, Cristina,Vlase, Laurian,Leonte, Denisa,Zaharia, Valentin
, p. 2602 - 2613 (2017/10/06)
Abstract: A series of pyridin-3/4-yl-thiazolo[3,2-b][1,2,4]triazole derivatives (5a–g, 6a–g) were synthesised by Hantzsch condensation of 5-pyridin-3/4-yl-1,2,4-triazole-3-thiol and diverse α-halocarbonyl compounds. Different reaction conditions (pH, temperature, solvent) were investigated for the efficient obtention of the target compounds. Under reflux and acidic conditions, the Hantzsch condensation was a one-step reaction. At room temperature and under basic conditions, it was possible to isolate the iminothioether intermediates 3/4a–g. These intermediates were cyclized in a subsequent step by treatment with concentrated sulphuric acid. The obtained compounds were evaluated for their anti-inflammatory activity. Three synthesised pyridyl-thiazolo[3,2-b][1,2,4]triazole derivatives (6c, 6d, 6f) were found to be good anti-inflammatory agents. Graphical Abstract: [InlineMediaObject not available: see fulltext.].
Synthesis and invitro Evaluation of West Nile Virus Protease Inhibitors Based on the 2-{6-[2-(5-Phenyl-4H-{1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide Scaffold
Samanta, Sanjay,Lim, Ting Liang,Lam, Yulin
, p. 994 - 1001 (2013/07/27)
In recent years, clinical symptoms resulting from West Nile virus (WNV) infection have worsened in severity, with an increased frequency in neuroinvasive diseases among the elderly. As there are presently no successful therapies against WNV for use in humans, continual efforts to develop new chemotherapeutics against this virus are highly desired. The viral NS2B-NS3 protease is a promising target for viral inhibition due to its importance in viral replication and its unique substrate preference. In this study, a WNV NS2B-NS3 protease inhibitor with a 2-{6-[2-(5-phenyl-4H-[1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide scaffold was identified during screening. Optimization of this initial hit by synthesis and screening of a focused compound library with this scaffold led to the identification of a novel uncompetitive inhibitor (1a24, IC50=3.4±0.2μM) of the WNV NS2B-NS3 protease. Molecular docking of 1a24 into the WNV protease showed that the compound interferes with productive interactions of the NS2B cofactor with the NS3 protease and is an allosteric inhibitor of the WNV NS3 protease.
