α-Neebisin derivatives and their preparation methods and applications

Abstract

The present invention provides an α-mangostin derivative having a structure of general formula I, a preparation method thereof, and an application of the same in preparing a drug for treating a brain injury caused by ischemia, such as vascular dementia and cerebral infarction. The vascular dementia is learning and memory impairment induced by a vascular disease or brain ischemia or cell loss in the dentate gyrus of the hippocampus.

Description

technical field

[0001] The present invention relates to α-azadirin derivatives, a preparation method of α-azadirin derivatives, and the application of α-azadirin derivatives in the preparation of drugs for treating ischemic brain injury, and belongs to the invention in the technical field of medicine. Background technique

[0002] Brain diseases caused by vascular lesions have become a serious threat to health, especially with the increasing number of elderly people in China, this problem has become more prominent. Cerebral infarction refers to ischemic necrosis or encephalomalacia of limited brain tissue caused by cerebral blood supply disturbance, ischemia, and hypoxia. The common clinical types of cerebral infarction include cerebral thrombosis, lacunar infarction, and cerebral embolism. , Cerebral infarction accounts for 80% of all strokes. Vascular dementia (vascular dementia, VD) is a dementia syndrome caused by brain tissue damage caused by cerebrovascular factors, a...

Examples

Embodiment 1

[0038] Embodiment 1: the synthesis (synthetic route figure such as figure 1 shown)

[0039]

[0040] Take α-Neebisin (40mg, 0.1mmol) in toluene solution, stir until dissolved, the solution turns yellow at this time, add 2,3-dichloro-5,6 dicyanoquinone (DDQ, 45mg, 0.2mmol) , reacted at 40°C, detected by TLC during the reaction, the reaction was completed after 5 hours, the toluene was distilled off under reduced pressure, separated and purified by silica gel column chromatography, and the yellow solid compound HZA was obtained with a yield of 85%.

[0041] Weigh BTC (60mg, 0.202mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add equivalent N-methylaniline, triethylamine (0.25mmol) and Add 5mL of dichloromethane slowly in an ice bath, remove the ice-salt bath after the addition, and stir at room temperature for 4 hours.

[0042] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, ...

Embodiment 2

[0044] Embodiment 2: the synthesis (synthetic route figure such as figure 1 shown)

[0045]

[0046] The synthetic method of compound HZA is the same as above.

[0047] Weigh BTC (58mg, 0.2mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add an equivalent amount of N-ethylaniline, triethylamine (0.25mmol) and Add 5mL of dichloromethane slowly in an ice bath, remove the ice-salt bath after the addition, and stir at room temperature for 4 hours.

[0048] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, and stir magnetically at room temperature until completely dissolved. Slowly add the solution dropwise to the reaction solution in the previous step under the ice-salt bath, remove the ice-salt bath after the dropwise addition, and stir at room temperature. After the reaction is completed, add 3 to 6 times the volume of distilled water to the above reaction solution, then extract...

Embodiment 3

[0050] Embodiment 3: the synthesis (synthetic route figure such as figure 1 shown)

[0051]

[0052] The synthetic method of compound HZA is the same as above.

[0053] Weigh BTC (58mg, 0.2mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add an equivalent amount of N-methyl-o-methylaniline, triethylamine (0.25 mmol) and 5mL of dichloromethane were slowly added dropwise in an ice bath, and the ice-salt bath was removed after the dropwise addition, and stirred at room temperature for 4h.

[0054] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, and stir magnetically at room temperature until completely dissolved. Slowly add the solution dropwise to the reaction solution in the previous step under the ice-salt bath, remove the ice-salt bath after the dropwise addition, and stir at room temperature. After the reaction is completed, add 3 to 6 times the volume of distilled water t...

technical field

[0001] The present invention relates to α-azadirin derivatives, a preparation method of α-azadirin derivatives, and the application of α-azadirin derivatives in the preparation of drugs for treating ischemic brain injury, and belongs to the invention in the technical field of medicine. Background technique

[0002] Brain diseases caused by vascular lesions have become a serious threat to health, especially with the increasing number of elderly people in China, this problem has become more prominent. Cerebral infarction refers to ischemic necrosis or encephalomalacia of limited brain tissue caused by cerebral blood supply disturbance, ischemia, and hypoxia. The common clinical types of cerebral infarction include cerebral thrombosis, lacunar infarction, and cerebral embolism. , Cerebral infarction accounts for 80% of all strokes. Vascular dementia (vascular dementia, VD) is a dementia syndrome caused by brain tissue damage caused by cerebrovascular factors, a...

Examples

Embodiment 1

[0038] Embodiment 1: the synthesis (synthetic route figure such as figure 1 shown)

[0039]

[0040] Take α-Neebisin (40mg, 0.1mmol) in toluene solution, stir until dissolved, the solution turns yellow at this time, add 2,3-dichloro-5,6 dicyanoquinone (DDQ, 45mg, 0.2mmol) , reacted at 40°C, detected by TLC during the reaction, the reaction was completed after 5 hours, the toluene was distilled off under reduced pressure, separated and purified by silica gel column chromatography, and the yellow solid compound HZA was obtained with a yield of 85%.

[0041] Weigh BTC (60mg, 0.202mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add equivalent N-methylaniline, triethylamine (0.25mmol) and Add 5mL of dichloromethane slowly in an ice bath, remove the ice-salt bath after the addition, and stir at room temperature for 4 hours.

[0042] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, ...

Embodiment 2

[0044] Embodiment 2: the synthesis (synthetic route figure such as figure 1 shown)

[0045]

[0046] The synthetic method of compound HZA is the same as above.

[0047] Weigh BTC (58mg, 0.2mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add an equivalent amount of N-ethylaniline, triethylamine (0.25mmol) and Add 5mL of dichloromethane slowly in an ice bath, remove the ice-salt bath after the addition, and stir at room temperature for 4 hours.

[0048] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, and stir magnetically at room temperature until completely dissolved. Slowly add the solution dropwise to the reaction solution in the previous step under the ice-salt bath, remove the ice-salt bath after the dropwise addition, and stir at room temperature. After the reaction is completed, add 3 to 6 times the volume of distilled water to the above reaction solution, then extract...

Embodiment 3

[0050] Embodiment 3: the synthesis (synthetic route figure such as figure 1 shown)

[0051]

[0052] The synthetic method of compound HZA is the same as above.

[0053] Weigh BTC (58mg, 0.2mmol) into a 25mL two-necked bottle, add 5mL of anhydrous dichloromethane, stir magnetically, add an equivalent amount of N-methyl-o-methylaniline, triethylamine (0.25 mmol) and 5mL of dichloromethane were slowly added dropwise in an ice bath, and the ice-salt bath was removed after the dropwise addition, and stirred at room temperature for 4h.

[0054] Add HZA (40mg, 0.1mmol) to a 10ml single-necked bottle, add a trace of DMAP, 5mL of dichloromethane, and stir magnetically at room temperature until completely dissolved. Slowly add the solution dropwise to the reaction solution in the previous step under the ice-salt bath, remove the ice-salt bath after the dropwise addition, and stir at room temperature. After the reaction is completed, add 3 to 6 times the volume of distilled water t...

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