CN1235599A - Biphenyl dicarboxylic acid derivatives and preparation thereof - Google Patents
Biphenyl dicarboxylic acid derivatives and preparation thereof Download PDFInfo
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- CN1235599A CN1235599A CN97199192A CN97199192A CN1235599A CN 1235599 A CN1235599 A CN 1235599A CN 97199192 A CN97199192 A CN 97199192A CN 97199192 A CN97199192 A CN 97199192A CN 1235599 A CN1235599 A CN 1235599A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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Abstract
The present invention relates to a novel biphenyl dicarboxylic acid derivative represented by formula (1), being effective for the treatment of liver disorder as well as hepatitis, and process for preparing them, wherein, M1 and M2 are the same or different, and each represents independently alkali metal atom.
Description
Background of invention
Invention field
The present invention relates to the represented novel biphenyl dicarboxylic acid derivatives of following formula (1), can effectively treat hepatic insufficiency and hepatitis, and relate to their preparation method
Wherein, M
1And M
2, can be identical or different, represent alkali metal atom separately.
Prior art is described
Generally speaking, biphenyl dicarboxylic acid derivatives can effectively be treated hepatitis, this point is appeared in the newspapers, particularly following formula (2) represented 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dimethyl ester (this paper is called " D.D.B ") Ceng Zuowei antihepatitis drug obtains commercial applications.
The represented D.D.B of following formula (2) that can effectively treat hepatic insufficiency is a kind of synthesis of derivatives, the similar chemical structure of schisandrin C that has Yu extract from schisandra fruit.The effect of D.D.B is to stop and virus, toxin or the relevant hepatocellular injury of medicine.D.D.B also can effectively strengthen liver function, and particularly to the serum transaminase value of hepatitis patient, promptly serum glutamic pyruvic transminase (this paper is called " S-GPT ") value is effective.The preparation method of D.D.B and physicals thereof have more detailed description in the clear and 60-209582 of Japanese Patent Laid publication number.
Although D.D.B is fine to S-GPT value normalizing effect aspect effect, make curative effect little [European patent application publication No. 90-353358] aspect serum glutamic oxalacetic transaminase (this paper is called " S-GOT ") the value normalizing.Shown in following formula (2), because its chemical structure generally is to be made of water-insoluble xenyl, methoxycarbonyl and alkyl phenyl ether, so D.D.B shows extremely low solubleness in water, less than 0.01% (W/W).In this respect, have and report, 26 1 phases of volume " solubilising of biphenyl dicarboxylic acid dimethyl ester and the design of its soft capsule "] owing to its absorptivity difference in gi tract causes bioavailability in the human body less than the pharmacology meeting of 30%[Korea S.
And because in fact D.D.B does not dissolve in water, it is mixed with oral liquid to desire or the injection form then is difficult to accomplish, therefore only limits to make solid form such as oral or capsule.
For overcoming the shortcoming of the represented D.D.B of following formula (2), the inventor is devoted for years to the development research of novel biphenyl dicarboxylic acid derivatives, a kind of hepatitis there is fabulous curative effect by synthetic, can makes the normal novel biphenyl dicarboxylic acid derivatives of S-GPT and S-GOT value simultaneously and finish the present invention.Because above-claimed cpd has very high solubleness in water, so can be mixed with oral liquid or injection.
Summary of the invention
It is a kind of that have a good curative effect to hepatopathy and can be mixed with some new type water-solubility biphenyl dicarboxylic acid derivatives as medicine types such as oral liquid or injections to the purpose of this invention is to provide, its preparation method and contain the pharmaceutical composition of this derivative as activeconstituents.
Brief description Fig. 1 a is 4,4 '-dimethoxy-5,6,5 ', the I.R spectrogram that 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid two is received; Fig. 1 b is 4,4 '-dimethoxy-5,6,5 ', H '-NMR spectrogram that 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid two is received; Fig. 2 a is 4,4 '-dimethoxy-5,6,5 ', the I.R spectrogram of 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid dipotassium; Fig. 2 b is 4,4 '-dimethoxy-5,6,5 ', the H '-NMR spectrogram of 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid dipotassium; Fig. 3 a is 4,4 '-dimethoxy-5,6,5 ', the I.R spectrogram of 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid potassium sodium; Fig. 3 b is 4,4 '-dimethoxy-5,6,5 ', the H ' of 6 '-two (methylene radical dioxy base) biphenyl dicarboxylic acid potassium sodium-NMR figure;
Detailed Description Of The Invention
The present invention relates to the represented biphenyl dicarboxylic acid derivatives of following formula (1):
Wherein, M1And M2Can be identical or different, represent separately alkali metal atom.
And, the invention further relates to the preparation method of the represented biphenyl dicarboxylic acid derivatives of following formula (1), this method comprises: the represented compound of formula (2) is distributed in the cosolvent of moisture and lower alcohol; Alkali hydroxide soln is joined in the said mixture reacting by heating; The regulator solution pH value is about 7, and decompression concentrates down; Acetone is added dropwise to above-mentioned solution makes its precipitation.
In addition, the invention still further relates to and contain the represented biphenyl dicarboxylic acid derivatives of following formula (1), contain the pharmaceutical composition that pharmacology can be accepted carrier simultaneously as activeconstituents.Be used for the treatment of hepatic insufficiency and hepatitis.
Hereinafter will explain the present invention in more detail.
The present invention relates to a kind of novel biphenyl dicarboxylic acid derivatives that has fabulous hepatoprotective effect and better solubleness is arranged in water.Thereby this derivative can be mixed with the medicine type of oral liquid or injection, is used for the treatment of hepatic insufficiency and hepatitis.
Specifically, by the present invention, the represented desirable biphenyl dicarboxylic acid derivatives of following formula (1) comprises 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid disodium, 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dipotassium, 4,4 ' dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid potassium sodium.
According to the present invention, the represented biphenyl dicarboxylic acid derivatives of following formula (1) prepares as follows:
At first, the represented D.D.B of following formula (2) is scattered in the cosolvent of moisture and lower alcohol.The amount ranges of cosolvent is preferably about 10～20 times of (weight) D.D.B, if cosolvent content is less than 10 times (weight), then the meltage as starting raw material D.D.B is few, causes speed of response slow excessively, and is if surpass 20 times (weight), then economical inadequately.The ratio of mixture of water and lower alcohol preferably maintains volume ratio 4: 6～6: 4 in 8: 2～2: 8 (volume) scopes.Such ratio be for the concentration of keeping starting raw material D.D.B and alkali metal hydroxide in constant scope.
Then, alkali hydroxide soln is joined in the above-mentioned dispersion soln, and under heating, reacted 4～10 hours.Therefore, the used alkali metal hydroxide of this reaction can be simplification compound or their mixture, and especially preferably uses sodium hydroxide, potassium hydroxide or their mixture.The alkali metal hydroxide amount among the D.D.B of adding is 1: 2.1～1: 2.2 equivalence ratio, if add-on is less than 2.1 equivalence ratios, then reaction is difficult to fully, and is if greater than 2.2 equivalence ratios, then economical inadequately.In addition, the temperature of described reacting by heating preferably maintains 70～90 ℃ temperature at 60～100 ℃, and less than 60 ℃, then speed of response becomes very slow as if temperature of reaction, if surpass 100 ℃, temperature of reaction will be above the boiling point of cosolvent.Therefore, any heating that exceeds the said temperature scope is all not ideal enough.
After described sufficient reacting carries out, the pH value of reaction soln is adjusted to 6～8, be preferably 7, decompression concentrates down then, obtains residue.The amount of acetone with 4～6 times of (weight) scopes is added in the residue, so that the represented compound precipitation of following formula (1).Preferably regulate pH value as neutralization reagent with 1NHCl.
For the purity of the compound that improves required following formula (1) expression, can use lower alcohol to carry out recrystallization in addition, obtain thus greater than 99.0% highly purified compound, yield is higher, greater than 90%.
According to the present invention, some lower alcohols that are used as reaction or recrystallization solvent in the preparation process are alkylol cpds of 1～3 carbon, more particularly, comprise methyl alcohol, ethanol, n-propyl alcohol and Virahol.If adopt some more than 4 carbon atoms replace lower alcohol than higher alcohols, then the solubleness of required compound significantly reduces, and makes yield become extremely low.
According to the aforesaid corresponding preparation method of the present invention, basic fundamental design is that some methyl groups in the methyl esters that connects of D.D.B key are taken off by basic hydrolysis, and then with alkalimetal ion chemical combination, be used to prepare water-soluble salt.
In general, directly take place rapidly more to be better than the method for oral preparations based on the method for injectable formulation in the medication of effect.In this respect, because the low solubility of D.D.B in water be less than 0.01% (W/W), want it actually is mixed with oral liquid or injection is difficult to reach.Comparatively speaking, the represented The compounds of this invention of following formula (1) has higher solubleness, and greater than 100% (W/W), its adoptable dosage form such as injection can deliver medicine to the patient who suffers from serious hepatic insufficiency very effectively.And, because the represented compound pH value in 10% aqueous solution of above-mentioned formula (1) presents 6～8,, can be used as the drug molecule that is fit to absorb thus and exist so can absorb rapidly by gi tract by oral administration.Therefore, its remarkable enhanced bioavailability will help further to reduce dosage.
Therefore, the present invention contains the represented biphenyl dicarboxylic acid derivatives of at least a or multiple following formula (1), so just can be mixed with some medicine type such as oral or injectable formulation.
Oral preparations comprises tablet, capsule, pill and oral liquid.Except that activeconstituents, solid preparation such as tablet, capsule and pill can be by containing some of appropriate amount commonly used and pharmacology acceptable carrier such as vehicle, binding agent, lubricant, bag agent, coating and sweet taste and prepare.Oral liquid also can comprise that water prepares as thinner by sweeting agent, flavouring agent, tinting material and the sanitas that contains appropriate amount.There is the injection of solution and powder to prepare by containing solvent commonly used, vehicle and sanitas.
The present invention does more detailed the explanation by the following examples, but is not subjected to the restriction of these embodiment.Embodiment 1: preparation 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid disodium.
With 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dimethyl ester (20g) joins in the cosolvent that contains pure water (100ml) and methyl alcohol (150ml), (purity 99%, 4.2g) solution slowly is added drop-wise in the described mixture under room temperature, lasts 1 hour will to be dissolved in the sodium hydroxide of pure water (50ml) then.After adding, reactor connects condenser, and temperature of reaction rises to 75～80 ℃, and stirred solution is 6 hours then.
After reaction was finished, 1N HCl is added dropwise to solution, and to regulate pH value be 7.0, and decompression concentrates down, obtains residue.(100ml) slowly is added dropwise to described residue with acetone, lasts 1 hour.Then, under room temperature, stirred the mixture 2 hours, obtain white powder behind the suction strainer.Powder obtains 19.8g title compound (yield 95.4%, purity 99.5%) with methyl alcohol (1 liter) recrystallization.The IR of this compound and H
1-NMR spectrogram is shown in Fig. 1 a and 1b respectively.Results of elemental analyses (C
18H
12O
10Na
2) theoretical value: C (49.77), H (2.76), O (36.87), Na (10.60) observed value: C (48.89), H (2.84), O (37.12), Na (10.43) embodiment 2: preparation 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dipotassium
Be prepared by top embodiment 1 described same steps as, outside the difference be with potassium hydroxide (purity 95%, 6.0g) replace sodium hydroxide (purity 99%, 4.2g).Obtain 21.4g white powder title compound (yield 96.0%, purity 99.8%) thus.The IR of this compound and H
1-NMR spectrogram is shown in Fig. 2 a and 2b respectively.Results of elemental analyses (C
18H
12O
10K
2) theoretical value: C (46.33), H (2.57), O (34.32), K (16.77) observed value: C (46.58), H (2.46), O (33.79), K (16.44) embodiment 3: preparation 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid potassium sodium
Be prepared by top embodiment 1 described same steps as, difference be with sodium hydroxide (purity 99%, 2.1g) and potassium hydroxide (purity 99%, 3.0g) replacement sodium hydroxide (purity 99%, 4.2g).Obtain 20.6g white powder title compound (yield 95.7%, purity 99.3%) thus.The IR of this compound and H
1-NMR spectrogram is shown in Fig. 3 a and 3b respectively.Results of elemental analyses (C
18H
12O
10NaK) theoretical value: C (47.99), H (2.67), O (35.55), Na (5.11), K (8.69) observed value: C (48.63), H (2.52), O (35.40), Na (5.23), K (8.37) experimental example 1: measure solubleness
Under room temperature, every kind of compound is dissolved in the 10ml distilled water to saturated.Then, leach concentrated aqueous solution and dry behind the insolubles.Measure the solubleness of every kind of compound by measuring residual quantity, the results are shown in following table 1.Table 1
| Compound | Solubleness (g/100ml water) |
| 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid disodium | Greater than 110 |
| 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dipotassium | Greater than 130 |
| 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid potassium sodium | Greater than 120 |
| D.B | 0.01 |
All be higher than 10,000 times of D.D.B by the water solubility of every kind of compound of the embodiment of the invention 1～3 preparation.Experimental example 2: test is to the effect of improving of hepatic insufficiency
Healthy male Sprague-Dawley mouse weighs 230～250g, is used for this test, estimates the improve effect of some compounds of described embodiment 1 and 2 preparations to hepatic insufficiency.
Experimental animal is divided into 4 groups, and (every group of 10 animals) are organized for first group in contrast, supplies with the 1ml pure water.Organize interior dosage oral D.D.B every day twice (totally 10 times) of five day time for second group as a comparison with 120mg/kg.The 3rd group then in five day time with the compound twice (totally 10 times) of oral embodiment 1 preparation dosage every day of 120mg/kg.The 4th group then in 5 day time with the compound twice (totally 10 times) of oral embodiment 2 preparations dosage every day of 120mg/kg.
After beginning to take medicine 4 days, the tetracol phenixin (1.2ml/kg) that is diluted in the equal-volume sweet oil is introduced the mouse body through intraperitoneal, to bring out liver injury.Introduce tetracol phenixin after 24 hours, mouse is anaesthetized, from aorta abdominalis, collect blood sample with ether.
After blood sample leaves standstill 1 hour, centrifugation.The serum of Huo Deing is used for measuring enzymic activity like this, as S-GOT, S-GPT and alkaline phosphatase.Test-results is shown in following table 2.Table 2.
| S-GPT(U/L) | s-GOT(U/L) | ALP(U/L) | |
| Control group | 1361±96 | 1798±135 | 384±51 |
| D.D.B. organize | 691±165 ** | 1821±386 | 285±37 * |
| Compound (embodiment 1) | 690±104 ** | 1000±215 ** | 239±25 * |
| Compound (embodiment 2) | 718±150 ** | 1143±278 | 227±18 * |
| *P＜0.05, **P＜0.01 | |||
It may be noted that with control group by last table 2 and to compare, can make the S-GPT value reduce to same level, can further make the ALP value descend manyly simultaneously than traditional D.D.B with traditional D.D.B by two kinds of compounds of the present invention.Make aspect the S-GOT reduction, do not observing any significantly differently between D.D.B group and control group, then presenting very significant curative effect by two kinds of compounds of the present invention, than the obviously reduction of S-GOT value of control group.
As mentioned above, the represented biphenyl dicarboxylic acid derivatives of following formula of the present invention (1) has following advantage: a) they can treat hepatic insufficiency well; B) because their the water-soluble conventional medicament that is much better than, so bioavilability is higher; C) can adopt various preparations to form. Therefore the compounds of this invention has larger improvement than conventional medicament.
In addition, preparation method of the present invention is very applicable to make industrial method, can obtain highly purified required compound by high yield, and preparation process is also relatively simple.
Therefore, the compounds of this invention can be used for making S-GPT and S-GOT value normal simultaneously very effectively, and in addition, because the compounds of this invention solubility in water is very high, it also can be used as oral liquid or injection is effective to improve liver function.
Claims (15)
1. the represented biphenyl dicarboxylic acid derivatives of following formula (1):
Wherein, M
1And M
2Can be identical or different, represent alkali metal atom separately.
2. according to the biphenyl dicarboxylic acid derivatives of claim 1, the represented compound of wherein said formula (1) is selected from 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid two receives, 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid dipotassium and 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy) biphenyl dicarboxylic acid potassium sodium.
3. the preparation method of the represented biphenyl dicarboxylic acid derivatives of following formula (1), this method comprises:
The represented compound of formula (2) is distributed in the cosolvent of moisture and lower alcohol;
Alkali hydroxide soln is joined in the said mixture reacting by heating;
The regulator solution pH value is about 7, and decompression concentrates down;
Acetone is added dropwise to above-mentioned solution makes its precipitation.
In the formula, M
1And M
2Can be identical or different, represent alkali metal atom separately.
4. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 3, wherein said alkali metal hydroxide is selected from sodium hydroxide and potassium hydroxide.
5. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 3 or 4, wherein said alkali metal hydroxide is simplification compound or their mixture.
6. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 5, wherein said alkali metal hydroxide uses with the equivalence ratio to the compound 2.1～2.2 of described formula (2) expression.
7. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 3, the cosolvent that wherein contains described water and lower alcohol mixed with volume ratio in 8: 2～2: 8.
8. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 7, the cosolvent that wherein contains described water and lower alcohol mixed with volume ratio in 4: 6～6: 4.
9. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 3, wherein said reacting by heating is carried out in 70～90 ℃ of scopes.
10. press the method for preparing biphenyl dicarboxylic acid derivatives of claim 3, wherein said precipitation lower alcohol recrystallization.
11. by the method for preparing biphenyl dicarboxylic acid derivatives of claim 3 or 10, wherein said hanging down is selected from methyl alcohol, ethanol, n-propyl alcohol and Virahol to alcohol.
12. contain the represented biphenyl dicarboxylic acid derivatives of following formula (1) as activeconstituents, contain the pharmaceutical composition that pharmacology can be accepted carrier simultaneously.
In the formula, M
1And M
2Can be identical or different, represent alkali metal atom separately.
13. according to the pharmaceutical composition of claim 12, pharmaceutical composition wherein is a kind of effective liver medicine, can be used for the treatment of hepatic insufficiency and hepatitis very effectively.
14. according to the pharmaceutical composition of claim 12, wherein said composition is an injection.
15. according to the pharmaceutical composition of claim 12, wherein said composition is an oral liquid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019960053721A KR100344099B1 (en) | 1996-11-13 | 1996-11-13 | Novel biphenyldicarboxylate derivative and method for manufacturing the same |
| KR1996/53721 | 1996-11-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1235599A true CN1235599A (en) | 1999-11-17 |
Family
ID=19481697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97199192A Pending CN1235599A (en) | 1996-11-13 | 1997-11-13 | Biphenyl dicarboxylic acid derivatives and preparation thereof |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JP2000503683A (en) |
| KR (1) | KR100344099B1 (en) |
| CN (1) | CN1235599A (en) |
| AU (1) | AU5068798A (en) |
| ID (1) | ID21896A (en) |
| WO (1) | WO1998021194A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100404527C (en) * | 2006-03-07 | 2008-07-23 | 河南省科学院质量检验与分析测试研究中心 | Chiral 4,4'-dimethoxy-5,6,5',6'-bis methylene dioxy -2,2'-phthalic acid derivatives and process for preparing same |
-
1996
- 1996-11-13 KR KR1019960053721A patent/KR100344099B1/en not_active IP Right Cessation
-
1997
- 1997-11-13 CN CN97199192A patent/CN1235599A/en active Pending
- 1997-11-13 ID IDW990270A patent/ID21896A/en unknown
- 1997-11-13 JP JP10522410A patent/JP2000503683A/en active Pending
- 1997-11-13 WO PCT/KR1997/000222 patent/WO1998021194A1/en active Application Filing
- 1997-11-13 AU AU50687/98A patent/AU5068798A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100404527C (en) * | 2006-03-07 | 2008-07-23 | 河南省科学院质量检验与分析测试研究中心 | Chiral 4,4'-dimethoxy-5,6,5',6'-bis methylene dioxy -2,2'-phthalic acid derivatives and process for preparing same |
Also Published As
| Publication number | Publication date |
|---|---|
| ID21896A (en) | 1999-08-05 |
| WO1998021194A1 (en) | 1998-05-22 |
| JP2000503683A (en) | 2000-03-28 |
| KR100344099B1 (en) | 2003-09-26 |
| AU5068798A (en) | 1998-06-03 |
| KR19980035382A (en) | 1998-08-05 |
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