CN105732627A - Medicinal application of evodiamine derivative - Google Patents
Medicinal application of evodiamine derivative Download PDFInfo
- Publication number
- CN105732627A CN105732627A CN201410766851.7A CN201410766851A CN105732627A CN 105732627 A CN105732627 A CN 105732627A CN 201410766851 A CN201410766851 A CN 201410766851A CN 105732627 A CN105732627 A CN 105732627A
- Authority
- CN
- China
- Prior art keywords
- compound
- pharmaceutically acceptable
- acid
- compounds
- rutaecarpin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- TXDUTHBFYKGSAH-UHFFFAOYSA-N CN(C1N2CCc3c1[nH]c1ccccc31)c1ccccc1C2=O Chemical compound CN(C1N2CCc3c1[nH]c1ccccc31)c1ccccc1C2=O TXDUTHBFYKGSAH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to evodiamine malate or a pharmaceutically acceptable solvate thereof, and application of the compounds in preparation of a medicine for preventing and treating rice blast.
Description
Invention field
The present invention relates to medicinal chemistry art, specifically, the present invention relates to the acylate of rutaecarpin derivant and medicinal usage thereof.
Background technology
For now, although the medicine of preventing and treating rice blast is existing a variety of, but these medicines existing easily cause drug resistance, and the prevention effect of some medicines is still not ideal enough.Chinese invention patent Authorization Notice No. is some reactive compounds with preventing and treating rice blast effect described in the patent documentation of CN1200608C.
Summary of the invention
The invention discloses some new compound, the preparation method of these compounds, pharmaceutical composition and the pharmacy of these compounds and compositions containing these compounds are applied.
These compounds show good water solublity stability and solid form stability.Some compound of these compounds shows special good stability.It has significantly high dissolubility to these compounds in water compared with corresponding free alkali.
These compounds show because of Synergistic between the two that compared with corresponding free alkali the activity of its preventing and treating rice blast is higher in surprise.
Surprising and the significant stability of these compounds, water solublity, preventing and treating rice blast activity be effective preparation and a large amount of use provides advantage.
Therefore, the invention provides a kind of formula III compound:
{(Ⅰ)H}+Ⅱˉ；
Wherein the chemical constitution of I is as follows:
Wherein the chemical constitution of II is as follows:
And/or pharmaceutically acceptable solvate, wherein:
ⅡˉRepresent counter ion counterionsl gegenions.
Suitable counter ion counterionsl gegenions IIˉIncluding the ion provided by pharmaceutically acceptable organic acid.
Preferred pharmaceutically acceptable organic acid includes cholic acid, chenodeoxycholic acid, ursodesoxycholic acid, deoxycholic acid, tartaric acid, maleic acid, malic acid, particularly malic acid.
Preferred counter ion counterionsl gegenions are malate ion.
Formula III compound is salt.
Suitable pharmaceutically acceptable solvate is hydrate.
Additionally, present invention also offers formula III and/or the preparation method of pharmaceutically acceptable solvate.The method includes formula I compound:
With counter ion counterionsl gegenions II defined aboveˉSource is reacted, hereafter if it is desirable, prepare its pharmaceutically acceptable solvate again.
Suitable counter ion counterionsl gegenions IIˉSource is pharmaceutically acceptable organic acid.
Preferred pharmaceutically acceptable organic acid includes cholic acid, chenodeoxycholic acid, ursodesoxycholic acid, deoxycholic acid, tartaric acid, maleic acid, malic acid, particularly malic acid.
Preferred source of counter ions is malic acid.
Formula I compound and counter ion counterionsl gegenions IIˉReaction between source usually carries out when conventional salt formation, such as, in a solvent, it is generally C1---C4 alkanol solvent such as ethanol, under the arbitrary temp generating required suitable rate can be provided, generally at the temperature of the temperature such as solvent refluxing raised, it is conveniently the mole about to wait but preferably with the counter ion counterionsl gegenions II of the amount of skipping overˉBy formula I compound and counter ion counterionsl gegenions II when sourceˉThen source mixing crystallizes out required product (III).
The pharmaceutically acceptable solvate of formula III compound can be prepared by conventional chemical method.
Formula I compound can the method described in the patent documentation that Chinese invention patent Authorization Notice No. is CN1200608C be prepared.
Suitable source of counter ions is known can easily to obtain through commercial sources, for instance malic acid, or can according to the required source of counter ions of known method preparation.
The stability of the compounds of this invention can use normal quantitative analysis method to measure；The stability of such as solid chemical compound can measure with the stability test accelerated, for instance differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA) is tested with the isothermal line in intensification.This test includes room temperature storage test.(wherein within known period when temperature and humidity control storage test compound).The quantitative analysis of test compound is before storage period, in storage period or after storage period.Stability relative to suitable reference standard determination test compound.
As it has been described above, the compound of the present invention it has significantly high dissolubility in water compared with corresponding free alkali.The conventional method so measuring the compounds of this invention stability in aqueous includes at known temperature conditions and measures in by the aqueous solution of test compound the degree being settled out parent free alkali in known period, it has been found that formula III compound demonstrates good aqueous stability.Particularly wherein IIˉThe formula III compound of the malate represented is particularly stable in aqueous.More surprisingly wherein IIˉStablizing of the formula III compound of the malate represented exception in aqueous.
Described test compound quantitative analysis test can in conventional manner, typically by chromatography, for instance high pressure lipuid chromatography (HPLC) carries out.
As it has been described above, the compound of the present invention has the therapeutic activity of practicality.
Therefore, the invention provides the formula III compound being used as preventing and treating rice blast active substance and/or pharmaceutically acceptable solvate.
So, the invention provides the formula III compound being used as preventing and treating rice blast and/or pharmaceutically acceptable solvate.
Formula III compound and/or pharmaceutically acceptable solvate can himself form be used, it is preferred that the form of the pharmaceutical composition that can also contain pharmaceutically acceptable carrier is used.
Therefore, present invention also offers a kind of pharmaceutical composition containing formula III compound and/or pharmaceutically acceptable solvate and pharmaceutically acceptable carrier.
Terminology used herein " pharmaceutically acceptable " includes compound, compositions and component that people and veterinary are used, for instance, term " pharmaceutically acceptable salt " includes the upper acceptable salt of veterinary.
Suitable pharmaceutical composition is the compositions of unit dosage forms, for instance oral liquid, tablet, capsule, injection, spray.
Optimum pharmaceutical composition is oral liquid, spray.
According to the convention on conventional medicine, carrier can include diluent, filler, disintegrating agent, wetting agent, lubricant, coloring agent, flavoring agent or other conventional additives.
Optimum compositions is arranged to unit dosage forms.
Generally, active component can aforementioned pharmaceutical compositions form be used.
Present invention also offers a kind of application on the medicine of preparation preventing and treating rice blast containing formula III compound and/or pharmaceutically acceptable solvate.
Embodiments of the invention are given below for further illustrating and being more fully described the present invention.
Embodiment 1
Rutaecarpin malate
Compound rutaecarpin 3.03 grams (0.01mol) and malic acid 1.34 grams (0.01mol) are dissolved in the ethanol 100 milliliters of boiling.This hot solution filters through kieselguhr, then Slow cooling under mild agitation, stands a few hours in the temperature environment of 05 DEG C, precipitate out rutaecarpin malate crystal, leach rutaecarpin malate crystal, dry with washing with alcohol and under 50 DEG C of vacuum conditions, obtain 4.27 grams of products.
Embodiment 2
Rutaecarpin malate
Compound rutaecarpin malate 3.03 grams and malic acid 1.34 grams are stirred in the ethanol 90 milliliters of backflow to solid and all dissolve.Add activated carbon, this hot solution is filtered through kieselguhr, stirring is cooled to room temperature.The temperature environment of 05 DEG C stands a few hours, precipitates out rutaecarpin malate crystal, leach rutaecarpin malate crystal, dry with washing with alcohol and under 50 DEG C of vacuum conditions, obtain 4.26 grams of products.
The present invention can summarizing without prejudice to the spirit of the present invention or the concrete form of principal character with other.Therefore, no matter from which point, the embodiment above of the present invention all can only think that the description of the invention can not limit the present invention.
Claims (2)
1. rutaecarpin (I) malic acid (II) salt (III)；
2. the compound of claim 1 application in preparation preventing and treating rice blast medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410766851.7A CN105732627A (en) | 2014-12-11 | 2014-12-11 | Medicinal application of evodiamine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410766851.7A CN105732627A (en) | 2014-12-11 | 2014-12-11 | Medicinal application of evodiamine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105732627A true CN105732627A (en) | 2016-07-06 |
Family
ID=56241434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410766851.7A Pending CN105732627A (en) | 2014-12-11 | 2014-12-11 | Medicinal application of evodiamine derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105732627A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107365322A (en) * | 2016-11-16 | 2017-11-21 | 中国药科大学 | A kind of new rutaecarpin analog derivative, preparation method and the usage |
| CN112438272A (en) * | 2020-12-03 | 2021-03-05 | 兰州大学 | Evodiamine analog and application thereof in preventing and treating plant pathogenic fungi |
-
2014
- 2014-12-11 CN CN201410766851.7A patent/CN105732627A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107365322A (en) * | 2016-11-16 | 2017-11-21 | 中国药科大学 | A kind of new rutaecarpin analog derivative, preparation method and the usage |
| CN107365322B (en) * | 2016-11-16 | 2019-07-19 | 中国药科大学 | A kind of novel rutaecarpin analog derivative, preparation method and the usage |
| CN112438272A (en) * | 2020-12-03 | 2021-03-05 | 兰州大学 | Evodiamine analog and application thereof in preventing and treating plant pathogenic fungi |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105732627A (en) | Medicinal application of evodiamine derivative | |
| CN105732625A (en) | Medicinal application of hydroxyevodiamine derivative | |
| CN105732499A (en) | Medicinal application of isoboldine derivative | |
| CN105732626A (en) | Medicinal application of rutaecarpine derivative | |
| CN105732474A (en) | Medicinal application of radix aristolochiae lactam derivative | |
| CN105732500A (en) | Medicinal application of isocorydine derivative | |
| CN105732475A (en) | Medicinal application of saurloactam derivative | |
| CN105732629A (en) | Medicinal application of sophoridine derivative | |
| CN103833757A (en) | Salt of methoxy-canthin-6-tone derivative | |
| CN104710422A (en) | Cytisine derivative | |
| CN105732496A (en) | Medicinal application of lotusine derivative | |
| CN105732607A (en) | Medicinal application of trimethoxy phenanthroquinolizidine derivative | |
| CN103908449A (en) | Salt of isocorydine derivative | |
| CN103772475A (en) | Conimine derivative salts | |
| CN103833758A (en) | Salt of hydroxyl canthin-6-one derivative | |
| CN103772383A (en) | Salts of evodiamine derivatives | |
| CN104447552A (en) | Pharmaceutical use of corydine derivative | |
| CN104387381A (en) | Drug application of hydroxyl phenanthroquinolizidine derivatives | |
| CN104710370A (en) | Pymetrozine derivative | |
| CN103508953A (en) | Salts of nuciferine derivatives | |
| CN103508952A (en) | Salts of N-nornuciferine derivatives | |
| CN104710418A (en) | Oleracein E derivativen | |
| CN103910724A (en) | Salt of picrasma quassioides alkaloid derivative | |
| CN104693116A (en) | N-deethyl diacetyl chasmanine derivative | |
| CN104710353A (en) | Pyridine alkaloid derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160706 |
|
| WD01 | Invention patent application deemed withdrawn after publication |