CN103374008A - Salt of chelerythrine derivative - Google Patents
Salt of chelerythrine derivative Download PDFInfo
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- CN103374008A CN103374008A CN2012101117865A CN201210111786A CN103374008A CN 103374008 A CN103374008 A CN 103374008A CN 2012101117865 A CN2012101117865 A CN 2012101117865A CN 201210111786 A CN201210111786 A CN 201210111786A CN 103374008 A CN103374008 A CN 103374008A
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- compound
- chelerythrine
- pharmaceutically acceptable
- iii
- formula
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Abstract
The invention relates to chelerythrine, fumarate of a derivative of the chelerythrine or a pharmaceutically acceptable solvate of the chelerythrine and applications of the chelerythrine, the fumarate and the solvate in preparation of medicaments for treating hepatitis B.
Description
Invention field
The present invention relates to the pharmaceutical chemistry field, particularly, the present invention relates to white chelerythrine organic acid salt and pharmacy thereof and use.
Background technology
For now, although the hepatitis b virus infected medicine for the treatment of is existing a variety of, existing these medicines easily cause many and heavy untoward reaction, the generation resistance that has, and the result for the treatment of of existing medicine is still not ideal enough.The Chinese invention patent application publication number is to have described some in the patent application of CN101084906A to have the active compound for the treatment of hepatitis B.
Summary of the invention
The invention discloses some novel compound, the preparation method of these compounds contains the pharmaceutical composition of these compounds and the pharmacy of these compounds and composition and uses.
These compound exhibits good water-soluble stability and solid form stability.The special good stability of some compound exhibits of these compounds.These compounds are compared with corresponding free alkali, and it has very high solvability in water.
These compounds are compared with corresponding free alkali and are shown that in surprise its anticancer activity is higher because of between the two synergy.
Effective preparation and a large amount of advantages that provide of using are provided surprising and significant stable, water-soluble, the antiviral activity of these compounds.
Therefore, the invention provides a kind of formula (III) compound:
{(I)H}+II
-；
Wherein the chemical structure of I is as follows:
Wherein the chemical structure of II is as follows:
And/or pharmaceutically acceptable solvate, wherein:
II
-The expression counter ion.
Suitable counter ion II
-The ion that is provided by pharmaceutically acceptable organic acid is provided.
The preferred acceptable organic acid of medicine comprises cholic acid, Chenodiol, ursodesoxycholic acid, Deoxycholic Acid, tartrate, toxilic acid, fumaric acid, particularly fumaric acid.
Preferred counter ion 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.This method comprises formula (I) compound:
Counter ion II with above-mentioned definition
-The source reaction after this if necessary, prepares its pharmaceutically acceptable solvate again.
Suitable counter ion II
-The source is pharmaceutically acceptable organic acid.
The preferred acceptable organic acid of medicine comprises cholic acid, Chenodiol, ursodesoxycholic acid, Deoxycholic Acid, tartrate, toxilic acid, fumaric acid, particularly fumaric acid.
Preferred source of counter ions is fumaric acid.
Formula (I) compound and counter ion II
-Reaction between the source is normally carried out under conventional salt-forming condition, for example, in solvent, be generally C1---C4 alkanol solvent such as ethanol, can provide under the arbitrary temp that generates required suitable speed, usually in the temperature that raises for example under the temperature of solvent refluxing, conveniently be with the molar weight that waits approximately but the slightly excessive counter ion II of preferred usefulness
-In the situation in source with formula (I) compound and counter ion II
-The source is mixed then crystallization and is gone out required product (III).
The pharmaceutically acceptable solvate of formula (III) compound can prepare with the chemical process of routine.
Formula (I) compound can be that the method for describing in the patent application of CN 101084906A prepares according to the Chinese invention patent application publication number.
Suitable source of counter ions is knownly can easily obtain through commercial approach, and for example fumaric acid perhaps can prepare according to known method required source of counter ions.
The stable available conventional quantitative analysis method of the compounds of this invention is measured; For example the stability of solid chemical compound can be measured with the stability test of accelerating, for example dsc (DSC), thermo-gravimetric analysis (TGA) and the test of the thermoisopleth in intensification.This test comprises the room temperature storage test.(in wherein during known under temperature and humidity control condition storage test compound).The quantitative analysis of test compound is before storage period, in storage period or after storage period.Stability with respect to 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 solvability in water.The ordinary method of measuring like this stability of the compounds of this invention in the aqueous solution be included in known temperature condition and known during in be settled out the degree of parent free alkali in the aqueous solution of mensuration by test compound, we go out good aqueous stability at discoverable type (III) compound exhibits.II wherein particularly
-Formula (III) compound of the fumaric acid radical of expression is stable especially in the aqueous solution.More surprised is II wherein
-Formula (III) compound of the fumaric acid radical of expression is unusual stablizing in the aqueous solution.
Described test compound quantitative analysis test can ordinary method, usually 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 pharmaceutically acceptable solvate as therapeutic active substance.
Like this, the invention provides as treatment and/or suppress hepatitis b virus infected formula (III) compound and/or pharmaceutically acceptable solvate.
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, composition and the component to people and animal doctor's use, and for example, term " pharmaceutically acceptable salt " comprises the upper acceptable salt of animal doctor.
Suitable pharmaceutical composition is the composition of unit dosage, for example oral liquid, tablet, capsule, injection liquid, sprays.
Optimum pharmaceutical composition is oral liquid, sprays.
According to the convention on the medicine of routine, carrier can comprise thinner, weighting agent, disintegrating agent, wetting agent, lubricant, tinting material, seasonings or other conventional additives.
Optimum composition is to be configured to unit dosage.
Usually, activeconstituents can the 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 hepatitis B virus.
The below provides embodiments of the invention and is used for further specifying and describing in more detail the present invention.
Embodiment 1
The white chelerythrine fumarate
Compound white chelerythrine 3.50 gram (0.01mol) and fumaric acid 1.17 are restrained in 80 milliliters of the ethanol that (0.01mol) be dissolved in boiling.This hot solution is through diatomite filtration, and then Slow cooling under mild stirring leaves standstill a few hours in 0-5 ℃ temperature environment, separate out white chelerythrine fumarate crystal, leach white chelerythrine fumarate crystal, with washing with alcohol and dry under 50 ℃ of vacuum conditions, get 4.63 gram products.
Embodiment 2
The white chelerythrine fumarate
Compound white chelerythrine fumarate 3.50 gram and fumaric acid 1.17 grams are stirred to solid in 80 milliliters of the ethanol of backflow all dissolve.Add gac, this hot solution through diatomite filtration, is cooled to room temperature in the stirring.In 0-5 ℃ temperature environment, leave standstill a few hours, separate out white chelerythrine fumarate crystal, leach white chelerythrine fumarate crystal, with washing with alcohol and dry under 50 ℃ of vacuum conditions, get 4.61 gram products.
The present invention can summarize with other the specific 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 be thought can not limit the present invention to explanation of the present invention.
Claims (2)
1. white chelerythrine (I) fumaric acid (II) salt (III);
{(I)H}+II
-
(III)。
2. the compound of claim 1 is in preparation treatment hepatitis B and/or slow down application in the hepatitis B virus infective medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101117865A CN103374008A (en) | 2012-04-16 | 2012-04-16 | Salt of chelerythrine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101117865A CN103374008A (en) | 2012-04-16 | 2012-04-16 | Salt of chelerythrine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103374008A true CN103374008A (en) | 2013-10-30 |
Family
ID=49459893
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101117865A Pending CN103374008A (en) | 2012-04-16 | 2012-04-16 | Salt of chelerythrine derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103374008A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015114163A3 (en) * | 2014-02-03 | 2015-10-29 | Hermann Roth | Composition for the prophylaxis or treatment of oxidative stress |
-
2012
- 2012-04-16 CN CN2012101117865A patent/CN103374008A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015114163A3 (en) * | 2014-02-03 | 2015-10-29 | Hermann Roth | Composition for the prophylaxis or treatment of oxidative stress |
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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: 20131030 |