CN110128473A - A kind of crystal form III of oxazolidinones antibacterials free acid and its preparation method and application - Google Patents
A kind of crystal form III of oxazolidinones antibacterials free acid and its preparation method and application Download PDFInfo
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- CN110128473A CN110128473A CN201910544648.8A CN201910544648A CN110128473A CN 110128473 A CN110128473 A CN 110128473A CN 201910544648 A CN201910544648 A CN 201910544648A CN 110128473 A CN110128473 A CN 110128473A
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- free acid
- crystal form
- antibacterials
- form iii
- oxazolidinones
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- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 66
- 229940088710 antibiotic agent Drugs 0.000 title claims abstract description 62
- 239000013078 crystal Substances 0.000 title claims abstract description 54
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 239000002253 acid Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000007787 solid Substances 0.000 claims abstract description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000012065 filter cake Substances 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002243 precursor Substances 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000001291 vacuum drying Methods 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 5
- 238000001228 spectrum Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 abstract description 10
- 239000007864 aqueous solution Substances 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 4
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 abstract 1
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229960003907 linezolid Drugs 0.000 description 2
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to crystal forms III of oxazolidinones antibacterials free acid and its preparation method and application, the preparation of crystal form III can effectively be solved, change crystallinity, the problem of further increasing stability and medical value in aqueous solution, method is, oxazolidinones antibacterials free acid precursor molecule is dissolved in 1, at solution in 4- dioxane, then the solution is added in hydrochloric acid solution at 0-5 DEG C, it is heated to 55 DEG C, it is stirred at room temperature 10 hours, it is cooled back to 0-5 DEG C, with NaOH tune pH value, continue to stir, filtering, filter cake is washed with methanol, filtering, it is dry, obtained oxazolidinones antibacterials free acid is added in solvent without fixed solid to be dissolved, it stirs at room temperature, filtering, filter cake vacuum drying, obtain crystal form III；The crystal form III of the method for the present invention preparation has water solubility well, has extraordinary stability in aqueous solution, is suitble to prepare pharmaceutical preparation or pharmaceutical composition, and then be prepared into antibacterials, has opened up the new way of antibacterials.
Description
Technical field
The present invention relates to medicine, especially a kind of crystal form III of oxazolidinones antibacterials free acid and preparation method thereof
And application.
Background technique
Due to abuse of the antibiotic in poultry feed and human diseases, bacterial resistance problem is caused to get worse, the mankind
The challenge of superbacteria will be faced in forthcoming years, and leads to the available situation of no medicine.Various countries increase novel antibacterial as a result,
The investment of medicament research and development, and gratifying achievement is achieved in recent years, including, disclosed in Chinese patent CN106478723B,
A kind of crystal form B of oxazolidinones antibacterials and its preparation method and application, shown in chemical structural formula such as formula (1):
Disclosed data shows that formula (1) compound represented has stronger inside and outside antibacterial activity compared with similar compound,
Better drug metabolism activity and lower drug toxicity.
But the study found that the crystal form of the molecular structural formula is different, performance is not identical, and drug effect is not also identical, especially ties
Brilliant degree is different, and stability in aqueous solution is not also identical, and the medicinal effects reached are not also identical, therefore, because small molecule
The crystal form for learning drug has important influence to the activity and stability of drug, and the present invention is prepared by the method for optimization crystallization
A kind of crystal form III of the oxazolidinones antibacterials free acid.A kind of oxazolidinones antibacterials free acid
Crystal form III have crystallinity high, stability in aqueous solution is good, is suitble to prepare pharmaceutical preparation or pharmaceutical composition, Jin Ergeng
It is suitable for being prepared into antibacterials, but so far there are no open report.
Summary of the invention
For above situation, for the defect for overcoming the prior art, the purpose of the present invention is just to provide a kind of oxazolidinones
Crystal form III of antibacterials free acid and its preparation method and application can effectively solve the preparation of crystal form III, change crystallinity, into
The problem of one step increase stability in aqueous solution and medical value.
The technical solution that the present invention solves is, a kind of crystal form III of oxazolidinones antibacterials free acid spreads out in X-ray
Penetrate in map comprising following 2 θ angle of reflection measurement characteristic peak: 5.4 ± 0.2 °, 8.6 ± 0.2 °, 10.9 ± 0.2 °, 12.4 ±
0.2°、16.8±0.2°、20.0±0.2°、21.1±0.2°、21.9±0.2°、22.3±0.2°、22.6±0.2°、24.1±
0.2 °, 24.9 ± 0.2 °, 26.2 ± 0.2 °, 27.4 ± 0.2 °, 29.8 ± 0.2 °, chemical structural formula are as follows:
The preparation method of the crystal form III the following steps are included:
(1), oxazolidinones antibacterials free acid precursor molecule is dissolved in Isosorbide-5-Nitrae-dioxane into solution,
Then the solution is added in hydrochloric acid solution at 0-5 DEG C, reaction mixture is heated to 55 DEG C, be stirred at room temperature 10 hours；It will
Reaction mixture is cooled to 0-5 DEG C, with NaOH tune pH value, continues 0-5 DEG C and stirs 1 hour, filtering, the methanol of 10 volumes of filter cake
It washes 2 hours, filters in 10-20 DEG C, it is dry, oxazolidinones antibacterials free acid is obtained without fixed solid；
(2), oxazolidinones antibacterials free acid is added in solvent without fixed solid and is dissolved, stirred at room temperature
10-80 hours, filtering, by filter cake 40-60 DEG C vacuum drying 16-36 hours, obtain described in crystal form III；
The solvent is methanol, ethyl alcohol, isopropanol, isobutanol, 2- butanone, acetonitrile, acetone, water, ethyl acetate, toluene
One of.
Application of the crystal form III of the oxazolidinones antibacterials free acid in preparation antibacterials.
The drug includes the crystal form III of oxazolidinones antibacterials free acid and one or more pharmaceutical
Carrier
The crystal form III of the method preparation has water solubility well, has extraordinary stability in aqueous solution, very
It is suitble to prepare pharmaceutical preparation or pharmaceutical composition, and then is prepared into antibacterials, has opened up the new way of antibacterials, improved
The medical value and commercial value of oxazolidinones antibacterials, there is significant economic and social benefit.
Detailed description of the invention
Fig. 1 is the X-ray diffracting spectrum figure of the crystal form III of oxazolidinones antibacterials free acid of the invention.
Fig. 2 is a month stability X-ray diffraction of the crystal form III of oxazolidinones antibacterials free acid of the invention
As a result figure is folded.
Specific embodiment
It elaborates below in conjunction with concrete condition to a specific embodiment of the invention.
Embodiment 1
In specific implementation, a kind of preparation method of the crystal form III of oxazolidinones antibacterials free acid is the present invention,
Reaction process formula are as follows:
According to above formula, a kind of preparation method of the crystal form III of oxazolidinones antibacterials free acid of the invention, including with
Lower step:
(1), the free acid precursor molecule of 100g is added in Isosorbide-5-Nitrae-dioxane of 4L and forms solution, then in 0-
5 DEG C are added to the solution in the hydrochloric acid solution of 30 equivalent of 6M, at reaction mixture；Reaction mixture is heated to 55 DEG C, in room
Temperature stirring 10 hours, is cooled back to 0-5 DEG C, adjusts pH value to 2-3 with the NaOH of 1 equivalent of 1M, it is small to continue at 0-5 DEG C of stirring 1
When, filtering, the methanol of 10 times of volumes of filter cake is washed 2 hours in 10-20 DEG C, is filtered, and it is dry, obtain oxazole shown in the formula (1) of 89g
Alkanone class antibacterials free acid is detected without fixed solid through efficient liquid phase, and the oxazolidinones antibacterials are free
Acid is 99.3% without fixed solid enantiomeric purity, and the total impurities including 6 diastereoisomers are 0.7%.
(2), 25g oxazolidinones antibacterials free acid is weighed without fixed solid, is added into 1000ml round bottom burning
In bottle, 525mL 2- butanone is added, stirs 50 hours at room temperature, filter cake is dried in vacuo 30 hours at 50 DEG C, obtains by filtering
III solid of 23g crystal form, yield 92%, obtained solid carry out powder x-ray diffraction, X-ray diffracting spectrum such as Fig. 1 institute
Show.
Embodiment 2
A kind of preparation method of the crystal form III of oxazolidinones antibacterials free acid of the present invention, weighs 1 step of 10g embodiment
Suddenly the oxazolidinones antibacterials free acid of (1) preparation adds water 200mL, stirs 60 hours at 40 DEG C, mistake without fixed solid
Filter cake is dried in vacuo 28 hours at 50 DEG C, obtains III solid of 8.8g crystal form, yield 88% by filter, and obtained solid carries out powder
X-ray diffraction, X-ray diffracting spectrum are as shown in Figure 1.
Crystal form III made by embodiment 1, embodiment 2 is through X-ray diffraction, includes following characteristics peak after measured: 5.4 ±
0.2°、8.6±0.2°、10.9±0.2°、12.4±0.2°、16.8±0.2°、20.0±0.2°、21.1±0.2°、21.9±
0.2°、22.3±0.2°、22.6±0.2°、24.1±0.2°、24.9±0.2°、26.2±0.2°、27.4±0.2°、29.8±
0.2 °, the crystal form crystallinity is high, and stability in aqueous solution is good, is suitble to prepare pharmaceutical preparation or pharmaceutical composition, and then make
It is standby at antibacterials, and through pharmacy test, drug effect has obtained large increase, and relevant information is as follows:
1, powder x-ray diffraction is tested:
Detecting instrument: Bruker D8Focus, LYNXEYE detector
Testing conditions:
As a result:
A kind of x-ray diffraction pattern of oxazolidinones antibacterials free acid crystal form III is shown in Fig. 1.
A kind of table 1: X- diffraction data of oxazolidinones antibacterials free acid crystal form III
2, In vivo antibacterial experiment:
Staphylococcus aureus (MRSA15-2) infecting mouse model is established according to the method for standard, with a kind of oxazolidone
Drug (testing drug) and Linezolid (control drug) the oral administration gavage administration that class antibacterials free acid crystal form III is prepared into
Infected mouse measures testing drug and control drug to the half effective dose (ED50) of infecting mouse, as a result such as table 2:
A kind of table 2: III antibacterial activity in vivo of oxazolidinones antibacterials free acid crystal form
The result shows that a kind of drug that oxazolidinones antibacterials free acid crystal form III is prepared into and control drug are oral
Gastric infusion has stronger Protective effect, a kind of oxazolidone to staphylococcus aureus MRSA 15-2 infecting mouse
The drug that class antibacterials free acid crystal form III is prepared into is 1.59mg/kg to the ED50 of infecting mouse, and interior curative effect is better than pair
According to medicine Linezolid more than 2 times, oxazolidinones antibacterials enantiomeric purity is greater than 99%, 6 diastereoisomers contained
For impurity summation inside less than 1%, oxazolidinones antibacterials enantiomeric purity is greater than 99%.
3, the stability experiment of a kind of oxazolidinones antibacterials free acid crystal form III in aqueous solution
The oxazolidinones antibacterials free acid crystal form III for weighing certain mass, places it in different temperatures and humidity item
It is saved under part, X-ray diffraction analysis is carried out after one month.Quality and condition used such as table 3.
A kind of table 3: III stability experiment condition of oxazolidinones antibacterials free acid crystal form
By Fig. 2 and table 3, the result shows that, the crystal form after high humidity hot conditions one month of crystal form III does not change, and shows non-
Often good stability.
Claims (9)
1. a kind of crystal form III of oxazolidinones antibacterials free acid, which is characterized in that include in X-ray diffracting spectrum
Below 2 θ angles of reflection measurement characteristic peak: 5.4 ± 0.2 °, 8.6 ± 0.2 °, 10.9 ± 0.2 °, 12.4 ± 0.2 °, 16.8 ±
0.2°、20.0±0.2°、21.1±0.2°、21.9±0.2°、22.3±0.2°、22.6±0.2°、24.1±0.2°、24.9±
0.2 °, 26.2 ± 0.2 °, 27.4 ± 0.2 °, 29.8 ± 0.2 °, chemical structural formula are as follows:
2. the crystal form III of oxazolidinones antibacterials free acid described in claim 1, which is characterized in that the crystal form III
X-ray diffracting spectrum it is as shown in Figure 1.
3. the preparation method of the crystal form III of oxazolidinones antibacterials free acid described in claim 1, which is characterized in that packet
Include following steps:
(1), at solution in Isosorbide-5-Nitrae-dioxane, then oxazolidinones antibacterials free acid precursor molecule is dissolved in
The solution is added in hydrochloric acid solution at 0-5 DEG C, reaction mixture is heated to 55 DEG C, is stirred at room temperature 10 hours；It will reaction
Mixture is cooled to 0-5 DEG C, with NaOH tune pH value, continues 0-5 DEG C and stirs 1 hour, filtering, the methanol of 10 volumes of filter cake in
10-20 DEG C is washed 2 hours, is filtered, dry, obtains oxazolidinones antibacterials free acid without fixed solid；
(2), oxazolidinones antibacterials free acid is added in solvent without fixed solid and is dissolved, stir 10- at room temperature
80 hours, filtering, by filter cake 40-60 DEG C vacuum drying 16-36 hours, obtain described in crystal form III；
The solvent is methanol, in ethyl alcohol, isopropanol, isobutanol, 2- butanone, acetonitrile, acetone, water, ethyl acetate, toluene
It is a kind of.
4. the preparation method of the crystal form III of oxazolidinones antibacterials free acid according to claim 3, feature exist
In the solution is 2- butanone.
5. the preparation method of the crystal form III of oxazolidinones antibacterials free acid according to claim 3, feature exist
In the solution is water.
6. the preparation method of the crystal form III of oxazolidinones antibacterials free acid according to claim 3, feature exist
In, comprising the following steps:
(1), the free acid precursor molecule of 100g is added in Isosorbide-5-Nitrae-dioxane of 4L and forms solution, then at 0-5 DEG C
The solution is added in the hydrochloric acid solution of 6M30 equivalent, at reaction mixture；Reaction mixture is heated to 55 DEG C, is stirred in room temperature
It mixes 10 hours, is cooled back to 0-5 DEG C, adjust pH value to 2-3 with the NaOH of 1M1 equivalent, continue at 0-5 DEG C and stir 1 hour, mistake
Filter, the methanol of 10 times of volumes of filter cake are washed 2 hours in 10-20 DEG C, are filtered, dry, obtain oxazolidinones antibacterials free acid
Without fixed solid；
(2), 25g oxazolidinones antibacterials free acid is weighed without fixed solid, is added into 1000ml round-bottomed flask,
525mL2- butanone is added, stirs 50 hours at room temperature, filter cake is dried in vacuo 30 hours at 50 DEG C, obtains 23g crystal form by filtering
III solid.
7. the preparation method of the crystal form III of oxazolidinones antibacterials free acid according to claim 3, feature exist
In, weigh 10g claim 5 step (1) preparation oxazolidinones antibacterials free acid without fixed solid, add water
200mL is stirred 60 hours at 40 DEG C, is filtered, and filter cake is dried in vacuo 28 hours at 50 DEG C, obtains III solid of 8.8g crystal form.
8. application of the crystal form III of oxazolidinones antibacterials free acid described in claim 1 in preparation antibacterials.
9. the crystal form III of oxazolidinones antibacterials free acid answering in preparation antibacterials according to claim 8
With, which is characterized in that the drug include oxazolidinones antibacterials free acid crystal form III and it is one or more can
Medicinal carrier.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478723A (en) * | 2016-09-09 | 2017-03-08 | 浙江普洛得邦制药有限公司 | A kind of crystal formation B of oxazolidinone antibacterial medicine and its preparation method and application |
| CN106478724A (en) * | 2016-09-09 | 2017-03-08 | 浙江普洛得邦制药有限公司 | A kind of crystal formation C of oxazolidinone antibacterial medicine and its preparation method and application |
| CN107892701A (en) * | 2016-10-03 | 2018-04-10 | 浙江普洛得邦制药有限公司 | The preparation method of Yi Zhong oxazolidinone antibacterials |
-
2019
- 2019-06-21 CN CN201910544648.8A patent/CN110128473A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106478723A (en) * | 2016-09-09 | 2017-03-08 | 浙江普洛得邦制药有限公司 | A kind of crystal formation B of oxazolidinone antibacterial medicine and its preparation method and application |
| CN106478724A (en) * | 2016-09-09 | 2017-03-08 | 浙江普洛得邦制药有限公司 | A kind of crystal formation C of oxazolidinone antibacterial medicine and its preparation method and application |
| CN107892701A (en) * | 2016-10-03 | 2018-04-10 | 浙江普洛得邦制药有限公司 | The preparation method of Yi Zhong oxazolidinone antibacterials |
Non-Patent Citations (1)
| Title |
|---|
| BIN GUO 等: "Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyl-oxazolidinones", 《J. MED. CHEM.》 * |
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Application publication date: 20190816 |