CN113735726A - 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate and preparation method thereof - Google Patents
2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate and preparation method thereof Download PDFInfo
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- CN113735726A CN113735726A CN202110906572.6A CN202110906572A CN113735726A CN 113735726 A CN113735726 A CN 113735726A CN 202110906572 A CN202110906572 A CN 202110906572A CN 113735726 A CN113735726 A CN 113735726A
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 title claims abstract description 20
- 235000010234 sodium benzoate Nutrition 0.000 title claims abstract description 20
- 239000004299 sodium benzoate Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 77
- 239000005711 Benzoic acid Substances 0.000 claims abstract description 32
- 235000010233 benzoic acid Nutrition 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000011734 sodium Substances 0.000 claims abstract description 16
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 15
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000000843 powder Substances 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000013078 crystal Substances 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 2
- 230000008014 freezing Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 239000000243 solution Substances 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 abstract description 2
- 239000012266 salt solution Substances 0.000 abstract 1
- 239000000376 reactant Substances 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 7
- 206010039966 Senile dementia Diseases 0.000 description 5
- 229910017053 inorganic salt Inorganic materials 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000003940 inhibitory effect on alzheimer disease Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036403 neuro physiology Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate and a preparation method thereof, wherein 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate is dissolved in pure water, sodium base is added, and sodium base is stirred for reaction to generate a 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate solution. The salt solution is frozen and dried to obtain the sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate. Compared with 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid, the salified product has better water solubility and stability. Is beneficial to the preparation, and simultaneously improves the dissolution performance and bioavailability of the finished product medicine. The process flow is simple, the operation is easy, and the potential utilization value is realized.
Description
Technical Field
The invention belongs to the field of preparation of pharmaceutical compounds, and particularly relates to 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate and a preparation method thereof.
Background
Senile dementia, Alzheimer Disease (AD), is a degenerative disease of the central nervous system that is mainly characterized by progressive cognitive impairment and memory impairment, and dementia is the most prominent mental symptom thereof. As the etiology and pathogenesis of the senile dementia are not known, a specific etiology treatment method is still lacked at present, but according to research findings of medical scientists for many years, a plurality of medicines have good effects on improving the memory capacity and cognitive function of senile dementia patients, delaying senility and the like. The research and development of the medicine for treating the senile dementia arouses high importance of the medicine world in various countries, and with the continuous and deep research on the aspects of neurophysiology, biochemistry, pharmacology and the like of the elderly, the development and research of related medicines are continuously advanced.
Korean reuuter corporation developed a compound having a superior therapeutic effect for treating neurological diseases such as alzheimer's disease and parkinson's disease, which is referred to as 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid;
the English name 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethyl) ] benzoic acid, and the structural formula is shown as follows.
Chinese patent CN101874016A discloses the compound and its preparation technology, and clinical tests show that the compound has better inhibitory effect on Alzheimer's disease. However, the solubility of the medicine in water at normal temperature and pressure is low, so that the dissolution rate of the prepared tablet is low, and the bioavailability is low.
Disclosure of Invention
The invention aims to provide 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate and a preparation method thereof, wherein the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid is salified to improve the solubility aiming at poor water solubility of the existing 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid, and the salified 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid is formed by reacting with an alkaline substance under certain conditions, so that the solubility and the bioavailability of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid are improved.
In order to solve the technical problems, the following technical scheme is adopted:
a preparation method of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate is characterized by comprising the following steps:
(1) adding a solvent into a reaction vessel, adding 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid into the reaction vessel, heating and stirring until the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid is completely dissolved to obtain a 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid solution;
(2) adding a certain amount of alkali into the reaction vessel, and stirring for 4-10 hours to ensure that the alkali and the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid fully react;
(3) and (3) carrying out post-treatment on the product obtained in the step (2) to obtain 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate crystal powder.
Preferably, in the step (1), the solvent is pure water, and the feed liquid mass ratio of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid to the solvent pure water is 1: 2, the temperature of the reaction solution is 60-80 ℃.
Preferably, the alkali in the step (2) is a sodium-based alkali selected from one of sodium hydroxide, sodium bicarbonate and sodium carbonate.
Preferably, the post-treatment step in the step (3) is: freezing the product at low temperature to solidify, and freeze drying.
2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate, and 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate crystal powder prepared by the preparation method.
Preferably, said crystalline powder of sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate has a melting point of 153 ℃.
Preferably, the crystalline powder of sodium-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate is off-white crystalline powder, and the main characteristic diffraction peak positions are 6.0 °, 12.5 °, 18.1 °, 19.5 °, 26.7 °, 30.4 °, 34.5 ° +/-0.2 ° in 2 θ.
Due to the adoption of the technical scheme, the method has the following beneficial effects:
according to the salification method of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid, the water solubility and stability of the salified product are better than those of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid. Because the water solubility of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid is poor, the solubility of the benzoic acid in water solution can be increased after salification, the absorption in vivo after preparation is facilitated, and the treatment effect of the finished product medicament is improved; the process flow is simple, the operation is easy, and the cost is low.
Drawings
The invention is further described with reference to the accompanying drawings in which:
FIG. 1 is an X-ray diffraction pattern (XRD) of an inorganic salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid according to the present invention;
FIG. 2 is a differential scanning spectrum (DSC) of inorganic salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid in accordance with the present invention;
FIG. 3 is an infrared spectrum (FTIR) of the inorganic salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid of the present invention;
FIG. 4 is a Scanning Electron Micrograph (SEM) of the inorganic salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid according to the present invention.
FIG. 5 is a photograph of nuclear magnetic resonance (1HNMR) of an inorganic salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid according to the present invention.
Detailed Description
The invention aims to provide 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate with simple process flow and low cost and a preparation method thereof.
The drug 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino)]Sodium benzoate is an off-white powder crystal with molecular formula C16H16NO3And (4) Na. The structural formula is as follows:
the corresponding main characteristic X-ray diffraction peaks are at 6.0 °, 12.5 °, 18.1 °, 19.5 °, 26.7 °, 30.4 °, 34.5 ° +/-0.2 °.
The characteristic diffraction peaks of the rays corresponding to the sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate are shown in the following table, and correspond to the attached figure 1:
the melting point of the sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate is 153 ℃ by thermal analysis (as shown in figure 2) and calculation; the enthalpy value is 122.4J/g.
The FTIR characteristic absorption peaks (shown in figure 3) of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate are 3422cm-1, 1916cm-1, 1581cm-1, 1501cm-1, 1330cm-1, 1167cm-1, 1128cm-1, 1070cm-1, 833cm-1,817cm-1, 703cm-1 and the like.
The 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino)]Sodium benzoate nuclear magnetic resonance chemical shift (as shown in figure 5)1HNMR(300MHz,D2O)δ7.67(dd,J＝16.3,8.3Hz),7.35(t,J＝10.1 Hz),7.27–7.02(m),7.00(d,J＝6.2Hz),6.89,6.68(dd,J＝6.5,1.8Hz),6.64–6.49 (m),6.43,2.92,2.50(d,J＝11.2Hz)。
The invention selects a proper amount of samples to test the dissolving capacity of the samples in water. The test shows that the solubility of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate in water at 25 ℃ is improved by about 5-8 times compared with the solubility of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid, and the sodium benzoate has better solubility and better bioavailability.
The invention is further illustrated by the following specific examples:
example 1
60 g of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid as a raw material was weighed into a flask, and pure water was added dropwise to the flask while stirring, and the mixture was dissolved in a 60 ℃ constant temperature water bath. And dropwise adding a certain amount of sodium hydroxide solution into the clear solution, keeping the temperature at 60 ℃ unchanged, fully reacting for 6 hours, taking out the reactant, placing the reactant into a beaker, and carrying out freeze drying treatment. The target product was obtained after 72 hours and the calculated yield after weighing the product was about 83%.
Example 2
30 g of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid as a starting material was weighed into a flask, and pure water was added dropwise to the flask while stirring, followed by dissolving in a 70 ℃ constant temperature water bath. And (3) dropwise adding a certain amount of sodium carbonate aqueous solution into the clear solution, keeping the temperature at 70 ℃ unchanged, fully reacting for 5 hours, taking out the reactant, placing the reactant into a beaker, and carrying out freeze drying treatment. The target product was obtained after 60 hours and the calculated yield after weighing of the product was about 87%.
Example 3
50 g of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid as a starting material was weighed into a flask, and pure water was added dropwise to the flask while stirring, followed by dissolving in a water bath at a constant temperature of 80 ℃. Dropping a certain amount of sodium bicarbonate water solution into the clear solution, keeping the temperature at 80 ℃, fully reacting for 9 hours, taking out the reactant, placing the reactant in a beaker, and carrying out freeze drying treatment. The target product was obtained after 72 hours and the calculated yield after weighing of the product was about 86%.
Example 4
40 g of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid as a starting material was weighed into a flask, and pure water was added dropwise to the flask while stirring, followed by dissolving in a water bath at a constant temperature of 80 ℃. And dropwise adding a certain amount of sodium carbonate aqueous solution into the clear solution, keeping the temperature at 75 ℃ unchanged, fully reacting for 6 hours, taking out the reactant, and placing the reactant in a rotary evaporator to remove the solvent. The solvent was evaporated until the solvent was completely removed to obtain an oily substance, and the sodium salt of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid could not be obtained.
The above is only a specific embodiment of the present invention, but the technical features of the present invention are not limited thereto. Any simple changes, equivalent substitutions or modifications made on the basis of the present invention to solve the same technical problems and achieve the same technical effects are all covered in the protection scope of the present invention.
Claims (7)
1. A preparation method of 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate is characterized by comprising the following steps:
(1) adding a solvent into a reaction vessel, adding 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid into the reaction vessel, heating and stirring until the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid is completely dissolved to obtain a 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid solution;
(2) adding a certain amount of alkali into the reaction vessel, and stirring for 4-10 hours to ensure that the alkali and the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid fully react;
(3) and (3) carrying out post-treatment on the product obtained in the step (2) to obtain 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate crystal powder.
2. The process for preparing sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate according to claim 1, wherein: in the step (1), the used solvent is pure water, and the feed liquid mass ratio of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoic acid to the solvent pure water is 1: 2, the temperature of the reaction solution is 60-80 ℃.
3. The process for preparing sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate according to claim 1, wherein: the alkali in the step (2) is sodium-based alkali selected from one of sodium hydroxide, sodium bicarbonate and sodium carbonate.
4. The process for preparing sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate according to claim 1, wherein: the post-treatment step in the step (3) is as follows: freezing the product at low temperature to solidify, and freeze drying.
5. A sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate characterized by: crystalline powder of sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate obtained by the production method according to claim 1.
6. A sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate according to claim 5, wherein: the melting point of the 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] sodium benzoate crystal powder is 153 ℃.
7. A sodium 2-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate according to claim 5, wherein: the sodium-hydroxy-5- [2- (4- (trifluoromethylphenyl) ethylamino) ] benzoate crystal powder is off-white crystal powder, and the main characteristic diffraction peak positions of the powder are 6.0 degrees, 12.5 degrees, 18.1 degrees, 19.5 degrees, 26.7 degrees, 30.4 degrees, 34.5 degrees +/-0.2 degrees at 2 theta.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022121854A1 (en) * | 2020-12-08 | 2022-06-16 | 吉恩特药业株式会社 | 2-hydroxy-5-[2-(4-(trifluoromethylphenyl)ethylamino)]benzoic acid crystal forms and preparation method therefor |
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| CN102316863A (en) * | 2009-02-09 | 2012-01-11 | 纽若泰克制药株式会社 | The medical usage of 5-benzylamino salicyclic acid derivatives or its salt |
| WO2020136441A1 (en) * | 2018-12-28 | 2020-07-02 | Gnt Pharma Co., Ltd. | Compositions and methods for treating neurodegenerative disorders |
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- 2021-08-09 CN CN202110906572.6A patent/CN113735726A/en active Pending
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| CN101426484A (en) * | 2006-04-13 | 2009-05-06 | 纽若泰克株式会社 | Pharmaceutical composition for treating or preventing degenerative and inflammatory diseases |
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| CN102316863A (en) * | 2009-02-09 | 2012-01-11 | 纽若泰克制药株式会社 | The medical usage of 5-benzylamino salicyclic acid derivatives or its salt |
| WO2020136441A1 (en) * | 2018-12-28 | 2020-07-02 | Gnt Pharma Co., Ltd. | Compositions and methods for treating neurodegenerative disorders |
Non-Patent Citations (1)
| Title |
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| 吴瑜亮 等: "抗阿尔茨海默病药物2-羟基-5-[2-(4-(三氟甲基苯基)乙基氨基)]苯甲酸的合成", 《CHINESE JOURNAL OF NEW DRUGS》 * |
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| WO2022121854A1 (en) * | 2020-12-08 | 2022-06-16 | 吉恩特药业株式会社 | 2-hydroxy-5-[2-(4-(trifluoromethylphenyl)ethylamino)]benzoic acid crystal forms and preparation method therefor |
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Application publication date: 20211203 |