CN103908449A - Salt of isocorydine derivative - Google Patents
Salt of isocorydine derivative Download PDFInfo
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- CN103908449A CN103908449A CN201310002562.5A CN201310002562A CN103908449A CN 103908449 A CN103908449 A CN 103908449A CN 201310002562 A CN201310002562 A CN 201310002562A CN 103908449 A CN103908449 A CN 103908449A
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- compound
- isocorydine
- pharmaceutically acceptable
- acid
- salt
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Abstract
The invention relates to an isocorydine fumarate or its pharmaceutically acceptable solvate and an application of isocorydine fumarate or its pharmaceutically acceptable solvate in preparation of medicines for treating HPV virus infection.
Description
Invention field
The present invention relates to pharmaceutical chemistry field, particularly, the present invention relates to acylate and the pharmacy application thereof of isocorydine alkali derivant.
Background technology
For now, although the medicine for the treatment of HPV viral infection is existing a variety of, existing these medicines easily cause many and heavy untoward reaction, some generation drug resistance, and the therapeutic effect of existing medicine is still not ideal enough.Chinese invention patent application publication No. is in the patent documentation of CN102389426 A, to have described some and have the reactive compound for the treatment of HPV viral infection.
Summary of the invention
The invention discloses some new compound, the preparation method of these compounds, the pharmacy application of the pharmaceutical composition that contains these compounds and these compounds and compositions.
These compounds have shown good water solublity stability and solid form stability.Some compound of these compounds shows special good stability.These compounds are compared with corresponding free alkali, and it has very high dissolubility in water.
These compounds are compared with corresponding free alkali and are shown that in surprise its antiviral activity is higher because of Synergistic between the two.
Surprising and the significant stability of these compounds, water solublity, antiviral activity are for effectively preparation and a large amount of use provide advantages.
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:
II-expression counter ion counterionsl gegenions.
Suitable counter ion counterionsl gegenions II-the comprise ion being provided by pharmaceutically acceptable organic acid.
The preferred acceptable organic acid of medicine comprises cholic acid, chenodeoxycholic acid, ursodesoxycholic acid, deoxycholic acid, tartaric acid, maleic acid, fumaric acid, particularly fumaric acid.
Preferred counter ion counterionsl gegenions are fumarate ions.
Formula III compound is salt.
Suitable pharmaceutically acceptable solvate is hydrate.
In addition, the present invention also provides the preparation method of formula III and/or pharmaceutically acceptable solvate.The method comprises formula I compound:
React with counter ion counterionsl gegenions defined above II-source, after this if necessary, then prepare its pharmaceutically acceptable solvate.
Suitable counter ion counterionsl gegenions II-source is pharmaceutically acceptable organic acid.
The preferred acceptable organic acid of medicine comprises cholic acid, chenodeoxycholic acid, ursodesoxycholic acid, deoxycholic acid, tartaric acid, maleic acid, fumaric acid, particularly fumaric acid.
Preferred source of counter ions is fumaric acid.
Reacting normally between formula I compound and counter ion counterionsl gegenions II-source carried out under conventional salt-forming condition, for example, in solvent, be generally C1---C4 alkanol solvent as ethanol, can provide under the arbitrary temp that generates required suitable speed, conventionally at the temperature of for example solvent refluxing of temperature raising, be conveniently mole approximately to wait but preferably formula I compound mixed to then crystallization with counter ion counterionsl gegenions II-source in the situation with slightly excessive counter ion counterionsl gegenions II-source and go out required product (III).
The pharmaceutically acceptable solvate of formula III compound can be prepared by conventional chemical method.
Formula I compound can be prepared by the method for describing in the patent documentation of CN 102389426A according to Chinese invention patent application publication No..
Suitable source of counter ions is knownly can easily obtain through commercial sources, for example fumaric acid, or can prepare required source of counter ions according to known method.
The stability of the compounds of this invention can be measured with conventional quantitative analysis method; The stability of for example solid chemical compound can be measured with the stability test accelerating, for example differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA) is tested with the isothermal line in intensification.This test comprises room temperature storage test.(in wherein during known under temperature and humidity controlled condition storage test compound).The quantitative analysis of test compound is before storage period, in storage period or after storage period.With respect to the stability of suitable reference standard determination test compound.
As mentioned above, compound of the present invention is compared with corresponding free alkali, and it has significantly high dissolubility in water.The conventional method of measuring like this stability of the compounds of this invention in aqueous solution be included in known temperature conditions and known during in be settled out the degree of parent free alkali in the aqueous solution of mensuration by test compound, we find that formula III compound demonstrates good aqueous stability.Particularly wherein the formula III compound of the fumaric acid radical of II-expression is stable especially in aqueous solution.More surprised is formula III compound abnormal stablizing in aqueous solution of the fumaric acid radical of wherein II-expression.
Described test compound quantitative analysis test can conventional method, conventionally uses chromatography, and for example high pressure lipuid chromatography (HPLC) is carried out.
As mentioned above, compound of the present invention has practical therapeutic activity.
Therefore, the invention provides formula III compound and/or the pharmaceutically acceptable solvate as therapeutic active substance.
Like this, the invention provides formula III compound and/or the pharmaceutically acceptable solvate as treatment and/or inhibition HPV viral infection.
Formula III compound and/or pharmaceutically acceptable solvate can himself form be used, and the form that preferably also can contain the pharmaceutical composition of pharmaceutically acceptable carrier is used.
Therefore, the present invention also provides a kind of pharmaceutical composition that contains formula III compound and/or pharmaceutically acceptable solvate and pharmaceutically acceptable carrier.
Term used herein " pharmaceutically acceptable " comprises compound, compositions and the component to people and veterinary's use, and for example, term " pharmaceutically acceptable salt " comprises the upper acceptable salt of veterinary.
Suitable pharmaceutical composition is the compositions of unit dosage forms, for example oral liquid, tablet, capsule, injection, spray.
Optimum pharmaceutical composition is oral liquid, spray.
According to the convention on conventional medicine, carrier can comprise diluent, filler, disintegrating agent, wetting agent, lubricant, coloring agent, flavoring agent or other conventional additives.
Optimum compositions is to be configured to unit dosage forms.
Conventionally, active component can aforementioned pharmaceutical compositions form be used.
The present invention also provides a kind of contain formula III compound and/or the application of pharmaceutically acceptable solvate on the medicine of production for treating and/or inhibition HPV virus.
Provide embodiments of the invention below for further illustrating and describe in more detail the present invention.
Embodiment 1
Isocorydine fumarate
Compound isocorydine 3.41 grams (0.01mol) and fumaric acid 1.17 grams (0.01mol) are dissolved in 90 milliliters of the ethanol of boiling.This hot solution is through diatomite filtration, and then Slow cooling under gentle agitation leaves standstill a few hours in the temperature environment of 0-5 ℃, separate out isocorydine fumarate crystal, leach isocorydine fumarate crystal, with washing with alcohol dry under 50 ℃ of vacuum conditions, obtain 4.57 grams of products.
Embodiment 2
Isocorydine fumarate
1.17 grams of 3.41 grams of compound isocorydine fumarates and fumaric acid are stirred to solid in 90 milliliters of ethanol refluxing all to be dissolved.Add active carbon, this hot solution, through diatomite filtration, is cooled to room temperature in stirring.In the temperature environment of 0-5 ℃, leave standstill a few hours, separate out isocorydine fumarate crystal, leach isocorydine fumarate crystal, with washing with alcohol dry under 50 ℃ of vacuum conditions, obtain 4.55 grams of products.
The present invention can summarize with other the concrete form without prejudice to spirit of the present invention or principal character.Therefore,, no matter from which point, above-mentioned embodiment of the present invention all can only think explanation of the present invention can not limit the present invention.
Claims (2)
1. isocorydine (I) fumaric acid (II) salt (III);
2. the compound of claim 1 is in preparation treatment and/or slow down the application in HPV virus infective medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310002562.5A CN103908449A (en) | 2013-01-04 | 2013-01-04 | Salt of isocorydine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310002562.5A CN103908449A (en) | 2013-01-04 | 2013-01-04 | Salt of isocorydine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103908449A true CN103908449A (en) | 2014-07-09 |
Family
ID=51034655
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310002562.5A Pending CN103908449A (en) | 2013-01-04 | 2013-01-04 | Salt of isocorydine derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103908449A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105616413A (en) * | 2016-01-25 | 2016-06-01 | 兰州大学 | Application of isoquinoline alkaloid as medicine used for preventing and treating cervical cancer |
-
2013
- 2013-01-04 CN CN201310002562.5A patent/CN103908449A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105616413A (en) * | 2016-01-25 | 2016-06-01 | 兰州大学 | Application of isoquinoline alkaloid as medicine used for preventing and treating cervical cancer |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140709 |