3-amino-4-indole-n-methyl maleimide compound, preparation and use thereof

Abstract

The invention relates to 3-amino-4-indo-N-methylmaleimide compounds and preparation and uses of the same. The general structural formula of the compounds is on the right. The preparation comprises a step that 3-bromo-4-indo-N- methylmaleimide reacts with various substituted amines at 80 to 95 DEG C in the presence of N,N- dimethyl formamide and triethylamine to form the 3-amino-4-indo-N-methylmaleimide compounds. The uses comprise use in the preparation of drugs of for preventing and treating tumor, diabetes and complications of the diabetes.

Description

Technical field

[0001] The invention relates to the field of amino-substituted indole maleimide compounds, in particular to a 3-amino-4-indole-N-methylmaleimide compound capable of preventing and treating tumors and diabetes complications. Imide compound and its preparation method and use. Background technique

[0002] In recent years, as people’s living standards have improved, industrial modernization has accelerated, chemicals have been widely used in food, cosmetics, and materials, and environmental pollution has increased. The incidence of gastric cancer, lung cancer, leukemia, and breast cancer has increased. An upward trend year by year. At present, the anti-tumor drugs used in the clinic such as Cyclophosphamide, Cisplatin, Fluorouracil, Doxifluridine, and folic acid anti-tumor drugs such as methotrexate There are disadvantages such as toxicity and lack of general anti-tumor effect.

[0003] In recent years, with the rapid development of tumor biology and related discipli...

Examples

Embodiment 1

[0033] Example 1 3-(1H-Indole-3)-4-(di-n-butylamino)-1-methyl-1H-pyrrole-2,5-dione

[0034]

[0035]0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.36g (2.8mmol) di-n-butylamine, 5mLN,N-dimethylformaldehyde Amide (DMF) and 0.2g (1.98mmol) of triethylamine were sequentially added to the flask, reacted at 90~95℃ for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined Organic phase, washed with water, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.45 g of dark red solid with a yield of 78%.

[0036] The properties of 3-(1H-indole-3)-4-(di-n-butylamino)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0037] This product is light red crystal, mp: 197~199℃;

[0038] IR (KBr): 3429, 1699, 1650, 1552, 1386, 745cm -1 ;3429cm in infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, ...

Embodiment 2

[0042] Example 2 3-(1H-Indole-3)-4-(isopropylamino)-1-methyl-1H-pyrrole-2,5-dione

[0043]

[0044] 0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.17g (2.8mmol) isopropylamine, 5mL N,N-dimethylformamide ( DMF), 0.2g (1.98mmol) of triethylamine, were sequentially added to a stirred flask, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), combined the organic phases , Washed, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.31 g of dark red solid with a yield of 67%.

[0045] The properties of 3-(1H-indole-3)-4-(isopropylamino)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0046] This product is light red crystal, mp: 203~206℃;

[0047] IR (KBr): 3448, 3319, 1700, 1647, 1615, 1549, 1385, 745cm -1 ;3448cm in infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, 1700...

Embodiment 3

[0051] Example 3 3-(1H-Indole-3)-4-(1-morpholinyl)-1-methyl-1H-pyrrole-2,5-dione

[0052]

[0053] 0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.20g (2.8mmol) morpholine, 5mL N,N-dimethylformamide ( DMF), 0.2g (1.98mmol) of triethylamine, were sequentially added to a stirred flask, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), combined the organic phases , Washed, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.44 g of dark red solid with a yield of 87%.

[0054] The properties of 3-(1H-indole-3)-4-(1-morpholinyl)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0055] This product is light red crystal, mp: 209~213℃;

[0056] IR (KBr): 3391, 3282, 1701, 1651, 1539, 1452, 1386, 746cm -1 ; 3391cm in the infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, 1701 ...

Technical field

[0001] The invention relates to the field of amino-substituted indole maleimide compounds, in particular to a 3-amino-4-indole-N-methylmaleimide compound capable of preventing and treating tumors and diabetes complications. Imide compound and its preparation method and use. Background technique

[0002] In recent years, as people’s living standards have improved, industrial modernization has accelerated, chemicals have been widely used in food, cosmetics, and materials, and environmental pollution has increased. The incidence of gastric cancer, lung cancer, leukemia, and breast cancer has increased. An upward trend year by year. At present, the anti-tumor drugs used in the clinic such as Cyclophosphamide, Cisplatin, Fluorouracil, Doxifluridine, and folic acid anti-tumor drugs such as methotrexate There are disadvantages such as toxicity and lack of general anti-tumor effect.

[0003] In recent years, with the rapid development of tumor biology and related discipli...

Examples

Embodiment 1

[0033] Example 1 3-(1H-Indole-3)-4-(di-n-butylamino)-1-methyl-1H-pyrrole-2,5-dione

[0034]

[0035]0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.36g (2.8mmol) di-n-butylamine, 5mLN,N-dimethylformaldehyde Amide (DMF) and 0.2g (1.98mmol) of triethylamine were sequentially added to the flask, reacted at 90~95℃ for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined Organic phase, washed with water, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.45 g of dark red solid with a yield of 78%.

[0036] The properties of 3-(1H-indole-3)-4-(di-n-butylamino)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0037] This product is light red crystal, mp: 197~199℃;

[0038] IR (KBr): 3429, 1699, 1650, 1552, 1386, 745cm -1 ;3429cm in infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, ...

Embodiment 2

[0042] Example 2 3-(1H-Indole-3)-4-(isopropylamino)-1-methyl-1H-pyrrole-2,5-dione

[0043]

[0044] 0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.17g (2.8mmol) isopropylamine, 5mL N,N-dimethylformamide ( DMF), 0.2g (1.98mmol) of triethylamine, were sequentially added to a stirred flask, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), combined the organic phases , Washed, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.31 g of dark red solid with a yield of 67%.

[0045] The properties of 3-(1H-indole-3)-4-(isopropylamino)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0046] This product is light red crystal, mp: 203~206℃;

[0047] IR (KBr): 3448, 3319, 1700, 1647, 1615, 1549, 1385, 745cm -1 ;3448cm in infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, 1700...

Embodiment 3

[0051] Example 3 3-(1H-Indole-3)-4-(1-morpholinyl)-1-methyl-1H-pyrrole-2,5-dione

[0052]

[0053] 0.5g (1.64mmol) 3-bromo-4-(1H-indole-3)-N-methylmaleimide, 0.20g (2.8mmol) morpholine, 5mL N,N-dimethylformamide ( DMF), 0.2g (1.98mmol) of triethylamine, were sequentially added to a stirred flask, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), combined the organic phases , Washed, anhydrous Na 2 SO 4 After drying and spin-drying the solvent, the mixed solvent of n-hexane and ethyl acetate (1:1) was recrystallized to obtain 0.44 g of dark red solid with a yield of 87%.

[0054] The properties of 3-(1H-indole-3)-4-(1-morpholinyl)-1-methyl-1H-pyrrole-2,5-dione are as follows:

[0055] This product is light red crystal, mp: 209~213℃;

[0056] IR (KBr): 3391, 3282, 1701, 1651, 1539, 1452, 1386, 746cm -1 ; 3391cm in the infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on indole, 1701 ...

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