Application of chukrasone A in the preparation of monoamine oxidase inhibitor drugs

Abstract

The invention relates to an application of Chukrasone A in preparing MAO (Monoamine Oxidase) inhibitor medicines. Compared with existing MAO inhibitors, the MAO inhibitor provided by the invention is greatly improved in inhibitory activity and selectivity to MAO-A and MAO-B. The use of the Chukrasone A for preparing MAO inhibitor medicines provided by the invention is disclosed for the first time. As the framework type belongs to a brand-new framework type, and the inhibitory activity of the Chukrasone A to MAO is unimaginably strong, the probability of giving any enlightenment by other compounds does not exist. The Chukrasone A has remarkable substantial characteristics and meanwhile has remarkable progress for treating diseases associated to MAO disorder.

Description

(1) Technical field

[0001] The invention relates to the application of Chukrasone A in the preparation of monoamine oxidase (MAO) inhibitors. (2) Background technology

[0002] Since the anti-tuberculosis drug isoniazid was found to be a potential MAO inhibitor, research on MAO inhibitors has become a hot topic. Iproniazid became the first MAO inhibitor, because it was discovered that this kind of MAO inhibitor containing hydrazine structure can also inactivate P450s and cause liver toxicity; and studied the non-hydrazine MAO inhibition represented by tranylcypromine Agents, this category can be called the second generation. But because "cheesereaction" causes high blood pressure, its application is limited. Therefore, it is quite necessary and urgent to develop a newer and more efficient monoamine oxidase inhibitor.

[0003] The compound ChukrasoneA involved in the present invention is a new skeleton compound published in 2012 (Liu, H.B.etal., 2012.ChukrasonesAandB: Pote...

Examples

Embodiment 1

[0012] Embodiment 1: the preparation of the compound ChukrasoneA tablet involved in the present invention:

[0013] Take 20 grams of compound Chukrasone A, add 180 grams of conventional excipients for tablet preparation, mix well, and make 1000 tablets with a conventional tablet press machine.

Embodiment 2

[0014] Embodiment 2: the preparation of the compound ChukrasoneA capsule involved in the present invention:

[0015] Get 20 grams of compound Chukrasone A, add conventional auxiliary materials for preparing capsules such as 180 grams of starch, mix well, and pack into capsules to make 1000 tablets.

[0016] The following pharmacodynamic experiments will further illustrate its drug activity.

[0017] Compound ChukrasoneA detects the inhibitory activity to MAO-A and MAO-B with the method of fluorescent probe, and described method is carried out according to the following steps:

[0018] Dissolve the sample to be tested in DMSO to prepare a series of samples with concentration gradient. Take 4ul of MAO (10mg / ml), boric acid buffer (PH=8.4), 50ul of BSA (50mg / ml), add the sample solution to be tested, mix well, react in a water bath at 30-38°C for 3h, then add probe 7- (3-Aminopropoxy)coumarin 2ul (50mmol / ml), inhibitor final concentration 0~10 -2 mmol / l, the mixture was then r...

(1) Technical field

[0001] The invention relates to the application of Chukrasone A in the preparation of monoamine oxidase (MAO) inhibitors. (2) Background technology

[0002] Since the anti-tuberculosis drug isoniazid was found to be a potential MAO inhibitor, research on MAO inhibitors has become a hot topic. Iproniazid became the first MAO inhibitor, because it was discovered that this kind of MAO inhibitor containing hydrazine structure can also inactivate P450s and cause liver toxicity; and studied the non-hydrazine MAO inhibition represented by tranylcypromine Agents, this category can be called the second generation. But because "cheesereaction" causes high blood pressure, its application is limited. Therefore, it is quite necessary and urgent to develop a newer and more efficient monoamine oxidase inhibitor.

[0003] The compound ChukrasoneA involved in the present invention is a new skeleton compound published in 2012 (Liu, H.B.etal., 2012.ChukrasonesAandB: Pote...

Examples

Embodiment 1

[0012] Embodiment 1: the preparation of the compound ChukrasoneA tablet involved in the present invention:

[0013] Take 20 grams of compound Chukrasone A, add 180 grams of conventional excipients for tablet preparation, mix well, and make 1000 tablets with a conventional tablet press machine.

Embodiment 2

[0014] Embodiment 2: the preparation of the compound ChukrasoneA capsule involved in the present invention:

[0015] Get 20 grams of compound Chukrasone A, add conventional auxiliary materials for preparing capsules such as 180 grams of starch, mix well, and pack into capsules to make 1000 tablets.

[0016] The following pharmacodynamic experiments will further illustrate its drug activity.

[0017] Compound ChukrasoneA detects the inhibitory activity to MAO-A and MAO-B with the method of fluorescent probe, and described method is carried out according to the following steps:

[0018] Dissolve the sample to be tested in DMSO to prepare a series of samples with concentration gradient. Take 4ul of MAO (10mg / ml), boric acid buffer (PH=8.4), 50ul of BSA (50mg / ml), add the sample solution to be tested, mix well, react in a water bath at 30-38°C for 3h, then add probe 7- (3-Aminopropoxy)coumarin 2ul (50mmol / ml), inhibitor final concentration 0~10 -2 mmol / l, the mixture was then r...

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