Delaid ingoticotramine -based cylinder phenolohol hybridization compound and its drug composition and application

An acyl phloroglucinol and compound technology, applied in the directions of drug combination, organic chemistry, pharmaceutical formulation, etc., can solve the problems of poor selectivity, insufficient drug efficacy, large side effects, etc., and achieve the effect of convenient operation

Active Publication Date: 2022-06-17
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, almost all of these molecules have problems such as poor selectivity, insufficient drug efficacy, and large side effects. There is still an urgent need for new late sodium current inhibitory active molecules in the market.

Method used

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  • Delaid ingoticotramine -based cylinder phenolohol hybridization compound and its drug composition and application
  • Delaid ingoticotramine -based cylinder phenolohol hybridization compound and its drug composition and application
  • Delaid ingoticotramine -based cylinder phenolohol hybridization compound and its drug composition and application

Examples

Experimental program
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Effect test

preparation example Construction

[0033] The present invention provides a method for preparing the compounds hypulatone A and hypulatone B described in the above technical solution, which includes the following steps: extracting the whole dried S. japonica (12kg) with methanol for 3 times, each time for 2 days, the obtained extract is reduced Press distillation to obtain an extract, mix the extract with 100-200 mesh silica gel, and perform silica gel column chromatography, the eluent used is chloroform, to obtain a chloroform segment, and then the obtained chloroform part is mixed with polyamide. 70%–100% methanol–water was used as the mobile phase to pass through the MCI column, and 5 components A to E were collected in sequence. The A (16.4 g) component was subjected to silica gel column chromatography under gradient elution conditions, and petroleum ether was used. / Acetone was used as eluent to collect 5 components in sequence, which were denoted as A1-A5 components; A2 component was separated and purified ...

Embodiment 1

[0043] The preparation method of compound hypulatone A and hypulatone B comprises the following steps:

[0044] The present invention provides a method for preparing the compounds hypulatone A and hypulatone B described in the above technical solution, which includes the following steps: extracting the whole dried S. japonica (12kg) with methanol for 3 times, each time for 2 days, the obtained extract is reduced Press distillation to obtain an extract, mix the extract with 100-200 mesh silica gel, and perform silica gel column chromatography, the eluent used is chloroform, to obtain a chloroform segment, and then the obtained chloroform part is mixed with polyamide. 70%–100% methanol–water was used as the mobile phase to pass through the MCI column, and 5 components A to E were collected in sequence. The A (16.4 g) component was subjected to silica gel column chromatography under gradient elution conditions, and petroleum ether was used. / Acetone was used as eluent to collect ...

Embodiment 2

[0059] The deararylated prenyl acylated phloroglucinol derivatives hypulatone A and hypulatone B of the present invention v 1.5 The experimental methods and results of late sodium current inhibitory activity are as follows:

[0060] 1. Cell Preparation and Expression

[0061] Human embryonic kidney (HEK) 293 cells were cultured in DMEM (HyClone) medium supplemented with 10% calf serum (Gibco) and dual antibodies to penicillin (100 units / ml), streptomycin (0.1 mg / ml) (Biological Industries) . 293 cells in logarithmic growth phase were treated with LipoD293 TM (SignaGen Laboratories) transfection reagent for human pCDNA3.1-Na v 1.5. pCDNA3.1-hERG, pCDNA3.1-K v 1.5. pCDNA3.1-Ca v 3.1 and pCDNA3.1-EGFP plasmids were transfected into cells. Transfected human embryonic kidney (HEK) 293 cells should be used within 48 hours.

[0062] 2. Electrophysiological experiments

[0063] All experiments were performed at room temperature (22-25°C). Borosilicate glass preparation pipettes...

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Abstract

The invention provides dearomatized isopentenyl acylated phloroglucinol heteroterpene hypulatone A and hypulatone B, their preparation method, and a pharmaceutical composition using them as active ingredients, which are used in medicine, especially in the treatment of myocardial ischemia , angina pectoris, arrhythmia and heart failure and other diseases in the drug application. The novel compounds hypulatone A and hypulatone B provided by the invention are heteroterpene compounds of sesquiterpene with complex structure and dearomatization isopentenyl acylated phloroglucinol. hypulatone A and hypulatone B have selective and significant inhibitory activity on late sodium currents, with significant Na v 1.5 Sodium ion channel inhibitory activity, among which the compound hypulatone B is currently the most active natural inhibitor, and its effect is 30 times that of the positive control ranolazine, which has obvious advantages and potential medicinal value. It can be used to prepare medicines for preventing and / or treating diseases of the heart system.

Description

technical field [0001] The present invention relates to the technical field of medicine, in particular to the v 1.5 The novel compounds hypulatone A and hypulatone B with sodium ion channel inhibitory activity and their preparation method, and their application in medicine for treating myocardial ischemia, angina pectoris, arrhythmia and heart failure. Background technique [0002] Hypericum is a large genus of the family Guttiferae, with about 400 species worldwide. There are about 55 species and 8 subspecies in my country, which are distributed all over the country, mainly in the southwest region. This genus is widely used as a medicinal plant at home and abroad and has a long history. For example, there are 25 species of Hypericum in my country which are used as medicine in the folk, and have various pharmacological activities such as antidepressant, antitumor, antiviral and antibacterial. So far, various types of active ingredients have been discovered from the genus ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D493/10A61K31/343A61P9/10A61P9/06
CPCC07D493/10A61P9/10A61P9/06
Inventor 许刚年寅叶岩松杜叔宗姜娜娜
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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