Substituted benzhydryl piperazine derivative and preparation method and application thereof

A technology of benzhydrylpiperazine and derivatives is applied in the field of substituted benzhydrylpiperazine derivatives and their preparation, and the preparation of brain neuroprotective agents, which can solve the problem of poor oral bioavailability and difficulty in permeating blood. Brain barrier, neurobehavioral toxicity, etc.

Active Publication Date: 2013-02-27
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Technical problem to be solved: one of the technical problems to be solved in the present invention is to disclose a substituted benzhydryl piperazine derivative with medical value, so as to overcome the problems in the prior art of inducing hemorrhage and difficulty in penetrating the blood-brain barrier , Poor oral bioavailability, low selectivity and high neurobehavioral toxicity

Method used

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  • Substituted benzhydryl piperazine derivative and preparation method and application thereof
  • Substituted benzhydryl piperazine derivative and preparation method and application thereof
  • Substituted benzhydryl piperazine derivative and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0044] (E)-3-(4-ethoxyphenyl)acrylic acid

[0045] Add 4-hydroxybenzaldehyde (5.09g, 0.0417mol) and water (25mL) into the reaction flask, heat up to 55°C, add tetrabutylammonium bromide (1.07g, 0.0033mol), wash with 30%wtNaOH solution Adjust the pH to make it alkaline. After the 4-hydroxybenzaldehyde is completely dissolved (the solution is orange-red), continue to heat up to boiling, reflux, and then add diethyl sulfate (6.68g, 5.66mL, 0.0433mol) dropwise, and finish dropping in 20 minutes , add 30%wt NaOH solution to ensure that the reaction solution is alkaline, after reflux for 20 hours, stop the reaction, separate the solution, dissolve the organic layer with 20mL toluene, wash with 5%wt NaOH solution (10mL*3), wash with water 3 times, dried over anhydrous magnesium sulfate, and evaporated to dryness to obtain 4.6 g of the product white solid 4-ethoxybenzaldehyde, yield 70.8%.

[0046] Add 4-ethoxybenzaldehyde (8.5g, 0.0566mol), malonic acid (8.8g, 0.0849mol), pyridine (...

Embodiment 2

[0048] (E)-3-(2-ethoxyphenyl)acrylic acid

[0049] The preparation method is the same as in Example 1, 2-hydroxybenzaldehyde (10.18g, 8.8mL, 0.0834mol), diethyl sulfate (13.36g, 11.3mL, 0.0866mol), tetrabutylammonium bromide (2.14g, 0.0066mol ), reflux reaction for 5.5 hours, to obtain 9 g of yellow liquid, yield 69.2%.

[0050] 2-Ethoxybenzaldehyde (15g, 0.0999mol), malonic acid (15.6g, 0.15mol), pyridine (68mL), hexahydropyridine (1.8mL), heated to 95°C to obtain 10.8g of white solid, Yield 56.3%.

Embodiment 3

[0052] (E)-3-(4-methylphenyl)acrylic acid

[0053] The preparation method is the same as in Example 1, 4-methylbenzaldehyde (12.0g, 0.1mol), malonic acid (15.6g, 0.15mol), pyridine (68mL), hexahydropyridine (1.8mL), heated to 95°C for reaction , 12.3 g of white solid was obtained, yield 75.9%, mp 195.1-196°C.

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Abstract

The invention relates to a substituted benzhydryl piperazine derivative and a preparation method and an application of the substituted benzhydryl piperazine derivative. The substituted benzhydryl piperazine derivative has a compound in structural formula (I): FORMULA. A part of compound provided by the invention is administrated preventively to prolong the survival time of mice suffering from acute cerebral ischemia so that the derivative has a certain neuroprotective effect of preventing cerebral ischemia. Thus, the compound provided by the invention can be used to prepare medicines for treating cerebral arterial thrombosis.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a substituted benzhydryl piperazine derivative, a preparation method thereof, and an application of the derivative in preparing a brain neuroprotective agent. Background technique [0002] Stroke is one of the diseases with the highest mortality and disability rate today, and nearly 80% of strokes are ischemic strokes. The survival of brain cells after a stroke depends on how much neurons are damaged, that is, how much blood flow to the brain that supplies cells with oxygen and nutrients is reduced. When ischemic stroke occurs, the cerebral blood flow in the ischemic core is severely reduced, and irreversible damage occurs to the brain tissue after 60-90 minutes; while the cerebral blood flow in the peripheral ischemic penumbra of the core is relatively reduced, but the cell metabolism Within a few hours after the occurrence of ischemia, the abnormal electrical activity and metabolic disor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/192C07D317/60A61P25/00A61P9/10
Inventor 吴斌滕言波戴兆慧许逸李萍张晓平
Owner NANJING MEDICAL UNIV
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