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 as the picture. 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 present 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 diseases such as tumors and diabetic complications. Imide compound and its preparation method and use. Background technique

[0002] In recent years, with the improvement of people's living standards, the acceleration of industrial modernization, the widespread use of chemicals in the fields of food, cosmetics and materials, and the aggravation of environmental pollution, the incidence of malignant tumors such as gastric cancer, lung cancer, leukemia and breast cancer has increased rapidly. rising trend year by year. At present, antineoplastic drugs such as cyclophosphamide (Cyclophosphamide), cisplatin (Cisplatin), fluorouracil (Fluorouracil), doxifluridine (Doxifluridine) and folic acid antineoplastic drugs such as methotrexate (methotrexate) used in clinical et...

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-dimethyl form Amide (DMF), 0.2g (1.98mmol) triethylamine were added to the flask in turn, reacted at 90-95°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), 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, 1699 and...

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, 5mLN, N-dimethylformamide ( DMF), 0.2g (1.98mmol) triethylamine, were added to a stirred flask in turn, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined the organic phases , 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 0.31 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 pea...

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, 5mLN, N-dimethylformamide ( DMF), 0.2g (1.98mmol) triethylamine, were added to a stirred flask in turn, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined the organic phases , 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 0.44 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 infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on...

technical field

[0001] The present 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 diseases such as tumors and diabetic complications. Imide compound and its preparation method and use. Background technique

[0002] In recent years, with the improvement of people's living standards, the acceleration of industrial modernization, the widespread use of chemicals in the fields of food, cosmetics and materials, and the aggravation of environmental pollution, the incidence of malignant tumors such as gastric cancer, lung cancer, leukemia and breast cancer has increased rapidly. rising trend year by year. At present, antineoplastic drugs such as cyclophosphamide (Cyclophosphamide), cisplatin (Cisplatin), fluorouracil (Fluorouracil), doxifluridine (Doxifluridine) and folic acid antineoplastic drugs such as methotrexate (methotrexate) used in clinical et...

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-dimethyl form Amide (DMF), 0.2g (1.98mmol) triethylamine were added to the flask in turn, reacted at 90-95°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), 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, 1699 and...

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, 5mLN, N-dimethylformamide ( DMF), 0.2g (1.98mmol) triethylamine, were added to a stirred flask in turn, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined the organic phases , 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 0.31 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 pea...

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, 5mLN, N-dimethylformamide ( DMF), 0.2g (1.98mmol) triethylamine, were added to a stirred flask in turn, reacted at 85°C for 10 hours, cooled to room temperature, added 20mL of water, extracted with ethyl acetate (20mL×3), and combined the organic phases , 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 0.44 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 infrared IR spectrum -1 Nearby are the N-H stretching vibration absorption peaks on...

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