1'-thio-aza indirubin compound, application and preparation method thereof

A technology of indirubin and compounds, which is applied in the field of medicine, can solve the problems that the anti-tumor effect of indirubin compounds has not been investigated, and achieve the effect of inhibiting or killing tumor cells

Inactive Publication Date: 2010-06-23
SHANGHAI JIAO TONG UNIV
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  • Abstract
  • Description
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Problems solved by technology

[0004] Chinese Invention Patent Application Publication CN101074229A (publication date: 2007.11.21) describes the introduction of a nitrogen atom at the 7-position of the indirubin nucleus, and the synthesis of 7-azaindirubin compounds with a new structure, which can overcome Indirubin compounds have the disadvantage of poor solubility and anti-tumor effect, but this article only changed the 7-position of the indirubin core structure, and did not investigate the effect of other heteroatoms on the anti-tumor effect of indirubin compounds influences

Method used

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  • 1'-thio-aza indirubin compound, application and preparation method thereof
  • 1'-thio-aza indirubin compound, application and preparation method thereof
  • 1'-thio-aza indirubin compound, application and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0048] 1′-Thio-7′-azaidirubin

[0049] Add 20mL methanol, isatin (76mg, 0.52mmol), thieno[2,3-b]pyridin-3-one (78mg, 0.52mmol) and anhydrous sodium carbonate (137mg, 1.29mmol) successively in a 50mL single-necked flask , stirred at room temperature for 6 h under nitrogen protection, and brown flocculent precipitates gradually precipitated. After filtration, the filter cake was washed successively with 50 mL of methanol, 50 mL of distilled water and 50 mL of methanol, and dried to obtain 125 mg of brown flocculent solid, yield 86.4%, mp>300°C. 1 H-NMR (300MHz, DMSO, δppm): 11.20 (s, 1H, NH), 8.99 (d, 1H, J=8.1Hz, H-4), 8.79 (dd, 1H, J=1.5Hz, 4.5Hz, H-6'), 8.22(dd, 1H, J=1.5Hz, 7.8Hz, H-4'), 7.40-7.49(m, 2H, H-6, 5'), 7.10(t, 1H, J= 8.1 Hz, H-5), 6.96 (d, 1H, J=7.8 Hz, H-7). IR (cm -1 , KBr): 3128, 3059, 1709, 1674, 1612, 1573, 1462, 1399, 1332, 1293, 1286, 1223, 1059, 1025, 1003, 761, 750, 740. ESI-MSm / z: 281.16[M+H] + .

Embodiment 2

[0051] 6-Fluoro-1′-thio-7′-azaidirubin

[0052] By 6-fluoroisatin and thieno [2,3-b] pyridin-3-one reaction in the system. Method is with embodiment 1.

[0053] Reddish-brown flocculent solid, yield 70.5%, mp>300°C. 1 H-NMR (300MHz, DMSO, δppm): 11.38(s, 1H, NH), 9.02-9.07(m, 1H, H-4), 8.79(dd, 1H, J=1.8Hz, 4.5Hz, H-6 '), 8.21(dd, 1H, J=1.8Hz, 7.5Hz, H-4'), 7.44-7.49(m, 1H, H-5'), 6.92(t, 1H, J=9.0Hz, H- 5), 6.77 (dd, 1H, J=2.7Hz, 9.0Hz, H-7). IR (cm -1 , KBr): 3119, 3073, 1722, 1678, 1621, 1578, 1498, 1450, 1408, 1333, 1298, 1153, 1136, 1055, 1005, 967, 846, 760, 743. ESI-MS m / z: 299.15[M+H] + .

Embodiment 3

[0055] 6-Chloro-1′-thio-7′-azaidirubin

[0056] By 6-chloro isatin and thieno [2,3-b] pyridin-3-one reaction in the system. Method is with embodiment 1.

[0057] Reddish-brown flocculent solid, yield 71.3%, mp>300°C. 1 H-NMR (300MHz, DMSO, δppm): 11.38(s, 1H, NH), 8.99(d, 1H, J=8.1Hz, H-4), 8.80(d, 1H, J=5.1Hz, H-6 '), 8.23 ​​(d, 1H, J=8.4Hz, H-4'), 7.45-7.50 (m, 1H, H-5'), 7.18 (d, 1H, J=8.1Hz, H-5), 6.99 (s, 1H, H-7). IR (cm -1 , KBr): 3119, 3074, 1722, 1679, 1613, 1576, 1454, 1443, 1406, 1326, 1294, 1098, 1050, 1003, 929, 853, 817, 758, 742. ESI-MS m / z: 313.2, 315.1 [M+H] + .

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Abstract

The invention discloses a 1'-thio-aza indirubin compound, application and a preparation method thereof, belonging to the field of medical technology. The preparation method of the compound comprises the steps of: respectively condensing 5-substituted, 6-substituted, 7-substituted isatin derivatives or 1-alkyl-7-azaindole-2,3-dione with thieno-(2,3-b)-pyridine-3-ketone or benzo-3(2H)-ketone to obtain a 1'-thio-aza indirubin compound in which R=O, wherein sodium carbonate is used as a catalyst; and reacting the 1'-thio-aza indirubin compound in which R=O with hydroxylamine to obtain a 1'-thio-aza indirubin compound in which R=NOH. The invention also relates to the application of the compound in the preparation of antineoplastic agents, acceptable salts in pharmacy synthesized by the compound with inorganic acid, organic acid or amino acid. The compound of the invention can suppress or kill tumor cells, have the character of anti-tumor activity and can be used for preparing medicines for treating tumors.

Description

technical field [0001] The invention relates to a compound in the technical field of medicine, its use and its preparation method, in particular to a 1'-thioazaidirubin compound, its use and its preparation method. Background technique [0002] Indirubin is clinically used to treat chronic myelogenous leukemia, but its solubility is poor, and it will cause side effects on the gastrointestinal tract. During clinical application, some patients have to stop taking the drug because of this. [0003] Find through literature search to prior art, Polychronopoulos, P. etc. published in " Journal of Medicinal Chemistry " (Journal of Medicinal Chemistry) 2004 the 47th phase 935~946 pages entitled " Structural basis for the synthesis of indirubins as potent and Selective inhibitors of glycogensynthase kinase-3 and cyclin-dependent kinases" (Structural basis of indirubin derivatives effectively selectively inhibiting glycogen synthesis kinase-3 and cyclin-dependent kinases), commented i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04C07D471/04A61K31/4365A61K31/437A61P35/00
Inventor 毛振民俞鸣烽张爱英
Owner SHANGHAI JIAO TONG UNIV
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