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Chemical Structure| 61394-50-1 Chemical Structure| 61394-50-1

Structure of 5-Cyanooxindole
CAS No.: 61394-50-1

Chemical Structure| 61394-50-1

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Product Citations

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Strang, Juliet E ; Astridge, Daniel D ; Chandler, Caleb ; Reigan, Phil ;

Abstract: AMP-activated protein kinase (AMPK) acts as a central cellular sensor at the interface of metabolic and signaling networks, that supports cell survival in energetically unfavorable environments. Due to its role in the direct mediation of fatty acid oxidation via acetyl-CoA carboxylase 2 (ACC2), there has been intensive development of small molecule activators for the treatment of metabolic diseases, such as and non-alcoholic fatty liver disease. In , inhibitors may be more effective in disrupting catabolic processes that support cell growth and survival. However, there has been little development of inhibitors and those that have been reported have limitations that prevent clinical evaluation. We have previously reported a structure-activity study of substituted oxindoles based on the multi-kinase inhibitor to determine the structural requirements for inhibition and found that a 5-(2-cyanoethyl)-substituted oxindole displayed selectivity for over VEGFR-2. Interestingly, the 5-cyano-oxindole has been reported as a GSK3β inhibitor and was also found to inhibit in a limited screen. Here, we report a further series of 3,5-substituted oxindoles that demonstrate that 5-cyano-oxindoles can inhibit both GSK3β and , but the 5-(2-cyanoethyl)-substitution and the orientation of the 3-substituent of the oxindole are critical determinants for inhibition and selectivity.

Keywords: ; GSK3β ; kinase ; oxindole ; small molecule inhibitor

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Product Details of [ 61394-50-1 ]

CAS No. :61394-50-1
Formula : C9H6N2O
M.W : 158.16
SMILES Code : N#CC1=CC2=C(NC(C2)=O)C=C1
MDL No. :MFCD02179599
InChI Key :NZOSLRYUVHMXTQ-UHFFFAOYSA-N
Pubchem ID :2773346

Safety of [ 61394-50-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H317-H319-H335
Precautionary Statements:P260-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338

Application In Synthesis of [ 61394-50-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 61394-50-1 ]

[ 61394-50-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 124467-36-3 ]
  • [ 61394-50-1 ]
  • 2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% With sodium hexamethyldisilazane; In tetrahydrofuran; at 110℃; for 0.166667h;Microwave irradiation; 3.3 2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbonitrileTo a suspension of <strong>[124467-36-3]2-chloro-7,8-dihydroquinolin-5(6H)-one</strong> (50 mg, 0.275 mmol) and 2-oxoindoline-5-carbonitrile (45.7 mg, 0.289 mmol) in tetrahydrofuran (1.4 mL) was added a 1.0 M solution of sodium bis(trimethylsilyl)amide (641 muL, 0.641 mmol). The mixture was stirred for 3 min at RT and then heated in a microwave oven to 110 C. for 10 min. After cooling to RT the reaction was quenched by addition of methanol (1 mL). The resulting solution was evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol) yielding an orange solid. Amount 17 mg. Yield 20%.1H-NMR (DMSO-d6, 400 MHz) delta 2.17 (m, 2H), 2.59 (t, 2H), 3.08 (t, 2H), 7.06 (d, 1H), 7.38 (dd, 1H), 7.68 (d, 1H), 7.98 (m, 2H), 11.11 (s, 1H), 14.78 (bs, 1H)MS (ES-API) m/z 304 (M+H+, 100%).
 

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