25045-82-3Relevant academic research and scientific papers
From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase
Juillet, Charlotte,Ermolenko, Ludmila,Boyarskaya, Dina,Baratte, Blandine,Josselin, Béatrice,Nedev, Hristo,Bach, Stéphane,Iorga, Bogdan I.,Bignon, Jér?me,Ruchaud, Sandrine,Al-Mourabit, Ali
, p. 1197 - 1219 (2021/02/05)
Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analogue EL-228 (1), whose structure could be optimized into the potent CJ2-150 (37). Here we present the synthesis of new inhibitors of Aurora B kinase, which is an important target for cancer therapy through mitosis regulation. The biologically oriented synthesis yielded several nanomolar inhibitors. The optimized compound CJ2-150 (37) showed a non-ATP competitive allosteric mode of action in a mixed-type inhibition for Aurora B kinase. Molecular docking identified a probable binding mode in the allosteric site "F"and highlighted the key interactions with the protein. We describe the improvement of the inhibitory potency and specificity of the novel scaffold as well as the characterization of the mechanism of action.
Synthesis, crystal structure and vibrational properties of N-(8-(3-(3-(tert-butyl)ureido)phenyl)imidazo[1,2-a]pyridin-6-yl)acetamide
Chen, Dongmei,Chen, Yumei,Liao, Weike,Wu, Qingmei,Zhang, Xiaohan,Zhou, Zhixu
, (2021/07/31)
Derivatives of imidazo[1,2-a]pyridine, a type of fused heterocyclic substance, play major roles in the chemical fields and are confirmed to be the core fragments of various drug molecules. In this study, the title compound was designed and synthesized from the coupling reaction of N-(8-iodoimidazo[1,2-a]pyridin-6-yl)acetamide and 1-(tert-butyl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea. The crystals of the title compound were obtained by solvent evaporation at room temperature. The structure of N-(8-(3-(3-(tert-butyl)ureido)phenyl)imidazo[1,2-a]pyridin-6-yl)acetamide was demonstrated by 1H NMR, 13C NMR, FT-IR and single crystal X-ray diffraction studies. Additionally, theoretical calculations, based on the density functional method B3LYP at the 6-311+G(d, p) level, were performed on the title compound, and the molecular structure optimized using DFT was consistent with the results obtained using X-ray diffraction. In addition, hydrogen bonding, intramolecular π–π stacking and the Van der Waals forces significantly stabilized of N-(8-(3-(3-(tert-butyl)ureido)phenyl)imidazo[1,2-a]pyridin-6-yl)acetamide, as shown in the packing diagram. Moreover, the vibrations of the title compound were reliably assigned on the basis of characteristic vibrational absorption bands. Finally, frontier molecular orbital (FMO) was employed to verify the charge transfer interaction involving the electron acceptor and electron donor groups.
Preparation process of 8-iodo-6-nitroimidazo[1,2-a]pyridine
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Paragraph 0026-0028; 0014-0016; 0020-0022, (2017/09/13)
The invention discloses a preparation process of 8-iodo-6-nitroimidazo[1,2-a]pyridine. The preparation process comprises the following step: by taking 2-amino-5-nitropyridine as a raw material, performing two-step reaction of cyclization and substitution to prepare the target product 8-iodo-6-nitroimidazo[1,2-a]pyridine. According to the route, the raw material is cheap and easily available, the 8-iodo product can be selectively obtained, the reaction conditions are mild, the process is simple to operate, and no organic metallic reagent causing severe environmental pollution is used, thereby being beneficial to environmental protection.
