- Development of imidazo[1,2- A[pyridine derivatives with an intramolecular hydrogen-bonded seven-membered ring exhibiting bright ESIPT luminescence in the solid state
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Imidazo[1,2-a]pyridine derivatives with different hydroxyaryl units (1-3), which could potentially form an intramolecular hydrogen-bonded seven-membered ring in either a planar or a twisted conformation, were newly developed, and the effect of conformatio
- Mutai, Toshiki,Muramatsu, Tatsuya,Yoshikawa, Isao,Houjou, Hirohiko,Ogura, Masaru
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- From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase
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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.
- 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
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p. 1197 - 1219
(2021/02/05)
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- N-(3-(IMIDAZO[1,2-B]PYRIDAZIN-3-YLETHYNYL)-4-METHYLPHENYL)-5-PHENYL-4,5-DIHYDRO-1H-PYRAZOLE-1-CARBOXAMIDE DERIVATIVE, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR TREATING KINASE-RELATED DISEASES
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The N-(3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylphenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide derivative exhibits excellent inhibitory activity against at least one kinase selected from the group consisting of ABL1, ABL2, AURKB, BRK, CDK11
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Paragraph 0315-0317
(2021/09/17)
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- BIARYL DERIVATIVE AND MEDICINE CONTAINING SAME
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Provided is a compound showing excellent antifungal activity against Trichophyton fungus, which is a major causative microorganism of superficial mycosis, and high effectiveness on diseases caused by Trichophyton fungi. A biaryl derivative represented by the formula (I) or a salt thereof: wherein ring A is an optionally substituted phenyl, or an optionally substituted 5- or 6-membered ring heteroaryl (ring A may be further condensed to form an optionally substituted fused ring); Q is CH2, C=O, NH, O, S or the like; X1, X2 and X3 are CR1 or N; Y is CH or N; Z is CR2b or N; R2a and R2b are each a hydrogen atom, a halogen atom, an optionally substituted C1-C6 alkyl group, a C1-C6 haloalkyl group or the like; R2a and R2b may form, together with carbon atoms bonded thereto, an optionally substituted carbocycle, or an optionally substituted heterocycle.
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Paragraph 0524
(2018/08/07)
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- PHARMACEUTICALS COMPRISING BIARYL DERIVATIVES OR SALTS THEREOF
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PROBLEM TO BE SOLVED: To provide compounds with excellent antimycotic activity against Trichophyton. SOLUTION: The invention provides pharmaceuticals comprising biaryl derivatives represented by general formula (I) or salts thereof, where ring A is optionally substituted phenyl or the like; Q is CH2 or the like; X1, X2 and X3 are CR1 or the like; and Y is CH or N. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0490
(2018/10/24)
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- METALLO-BETA-LACTAMASE INHIBITORS
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The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.
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Page/Page column 84
(2017/04/04)
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- Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators
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The design and the synthesis of several chemical subclasses of imidazole containing γ-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo p
- Bischoff, Francois,Berthelot, Didier,De Cleyn, Michel,MacDonald, Gregor,Minne, Garrett,Oehlrich, Daniel,Pieters, Serge,Surkyn, Michel,Trabanco, Andres A.,Tresadern, Gary,Van Brandt, Sven,Velter, Ingrid,Zaja, Mirko,Borghys, Herman,Masungi, Chantal,Mercken, Marc,Gijsen, Harrie J. M.
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supporting information
p. 9089 - 9106,18
(2020/10/15)
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