CN102381972B - Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof - Google Patents
Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof Download PDFInfo
- Publication number
- CN102381972B CN102381972B CN 201110263939 CN201110263939A CN102381972B CN 102381972 B CN102381972 B CN 102381972B CN 201110263939 CN201110263939 CN 201110263939 CN 201110263939 A CN201110263939 A CN 201110263939A CN 102381972 B CN102381972 B CN 102381972B
- Authority
- CN
- China
- Prior art keywords
- disoprofol
- propofol
- ester
- compound
- acid ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Disclosed are a propofol hydroxy acid ester compound with an ester constitutional terminal, a preparation method for the same and application thereof. As shown in the constitutional formula (I) of the compound, Y refers to a C1-4 linear carbon chain, and R refers to acetyl or propiono. The propofol hydroxy acid ester compound can be prepared by utilizing corresponding propofol hydroxy acid ester as raw materials and is obtained by means of esterification reaction with corresponding acid anhydride. As experiments show, the compound is stable in vitro but capable of quickly releasing propofol with sedation and hypnogenesis and/or narcotism in blood plasma. Since hydroxy in propofol hydroxy butyric ester molecules is protected by means of shielding, heat stability of the propofol hydroxy acid ester compound is improved, and self-decomposition of the propofol hydroxy acid ester compound caused by lactonization is reduced.
Description
Technical field
The present invention relates to a kind of derivative of Disoprofol, specifically is a kind of Disoprofol alcohol ester compounds with the ester structure end, with and preparation method thereof and application in pharmacy.
Background technology
Disoprofol (Propofol), chemical name is 2,6-Bis(1-methylethyl)phenol, be at present clinically the general anesthesia of widespread use induce, keep and the downern during Intensive Care Therapy, have rapid-action, the characteristics that the metabolism inactivation is fast.This compound has progressively been applied in worldwide since 1977 make clinical report first.Disoprofol also finds to have other many-sided pharmacological actions except the pharmacological action aspect anesthesia, such as anti-epileptic, treatment migraine etc., therefore the research that oral propofol is derived become study hotspot.Because Disoprofol has very significant first pass effect, need to modify to reduce first pass effect to it.And if the propofol derivative after modifying can not discharge the former medicine of Disoprofol fast, can't play again the pharmacological action of expectation.Therefore, to the research through the propofol derivative of various chemically modifieds, be a present hot subject.
Summary of the invention
In view of the foregoing, the present invention at first provides a kind of Disoprofol alcohol ester compounds with the ester structure end, and the preparation method of this compound further is provided, and the application of this compound in pharmacy.
The present invention is with the Disoprofol alcohol ester compounds of ester structure end, structure shown in formula I,
（Ⅰ）
Y in the formula is C
1 ~ 4The straight chain carbochain, R is ethanoyl or propionyl.
The Y of above-mentioned formula I structure is preferably saturated carbon chains.Further more preferably Y is-CH
2-CH
2-or-CH
2-CH
2-CH
2-.
On the basis of said structure, the straight chain carbochain Y in the above-mentioned formula I structure also allows for the form that has at least a H to be replaced by the group that comprises methyl, ethyl, cyclopropyl, hydroxyl, sulfydryl, amino or substituted-amino on it.
The preparation with the Disoprofol alcohol ester compounds of ester structure end of structure shown in the above-mentioned formula I of the present invention, can be raw material with the disclosed Disoprofol alcohol ester (II) of publication number CN101906039A, obtain formula I structural object product with diacetyl oxide or propionic anhydride through esterification.Experiment shows that this esterification can both be carried out usually smoothly under 0 ℃ ~ 95 ℃ condition.According to different temperature of reaction, reaction can be finished in 30 minutes to 24 hours.Wherein, the Y in the raw material formula II structure is C
1 ~ 4The straight chain carbochain.
（Ⅱ）
Because one of raw material that above-mentioned esterification is used is diacetyl oxide or propionic anhydride, so this esterification carries out under the condition that has the disacidify agent to exist, and obviously is more favourable.Wherein said disacidify agent can be selected by the usual manner of this type of reaction.The disacidify agent of recommendation among the present invention can be preferably and has more alkaline pyridine or comprise the tertiary amine compounds such as triethylamine.
Experiment shows, the esterification of the above-mentioned preparation process of the present invention, generally can be chosen in the similar esterification and carry out in the normally used reaction medium solvent, as selecting to comprise at least a as reaction solvent in methylene dichloride, chloroform, tetracol phenixin, chlorobenzene, benzene, toluene, sherwood oil, hexanaphthene, normal hexane, acetonitrile, acetone, DMF, DMSO, tetrahydrofuran (THF), ether, triethylamine or the pyridine.Wherein, preferred reaction solvent is doublely to do triethylamine or the pyridine that acid scavenger uses simultaneously.
Above-mentioned esterification can also be carried out under the condition of reactionless solvent except can carrying out in said solvent medium.
In as preparation the compounds of this invention raw material formula II compound; although the phenolic hydroxyl group in the Disoprofol and hydroxycarboxylic acid have obtained shielding after forming ester; protected the first hydroxyl of being attacked in the elimination of crossing of Disoprofol; reduced the ability of Disoprofol first pass metabolism; but compound (II) is not good in external stability, especially to thermo-responsive.In order to increase the thermostability of compound (II), through great many of experiments and research, the present invention has designed the Disoprofol alcohol ester compounds with the ester structure end of formula I structure formation, and proved Disoprofol alcohol ester that this formula I compound can not only effectively overcome formula II external to heat-labile shortcoming, improved its stability, and have in blood plasma and can discharge quickly the characteristics that produce the Disoprofol with tranquilizing soporific and/or anaesthetic effect, and the alcohol acid that discharges and corresponding esterification products do not have toxicity for human body yet.Thereby the compound of above-mentioned formula I structure formation is as the prodrug of Disoprofol, be configured to the pharmaceutically formulation such as acceptable emulsion, outside vein or the vein approach of can be used as is used the maincenter suppressive drug that the animal or human produces tranquilizing soporific and/or anesthetic action, and can produce desirable effect.
Below in conjunction with the embodiment by the accompanying drawing illustrated embodiment, foregoing of the present invention is described in further detail again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.Do not breaking away from the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made all should comprise within the scope of the invention.
Description of drawings
Fig. 1 is the mass spectrum of the acetic ester of embodiment 1 Disoprofol butyric ester.
Fig. 2 is the mass spectrum of the propionic ester of embodiment 5 Disoprofol butyric esters.
Fig. 3 is the mass spectrum of the acetic ester of embodiment 9 Disoprofol hydroxyl valerates.
Fig. 4 is the mass spectrum of the propionic ester of embodiment 10 Disoprofol hydroxyl valerates.
Fig. 5 is the external rabbit plasma rate of decomposition of the ester compound graphic representation of the different Disoprofol alcohol esters of the present invention.
Embodiment
Embodiment 1
The preparation of the acetic ester of Disoprofol butyric ester:
4 g are dissolved in 20 ml methylene dichloride with the Disoprofol 4 hydroxybutyric acid ester that the mode of publication number CN101906039A prepares, add 10 ml acetic anhydride, be cooled to 0 ℃, drip 3 ml triethylamines, keep temperature stirring reaction 24 h, react and reaction solution is poured in the 100 ml water after complete, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure by column chromatography for separation and wash-out after (elutriant (v/v, below all herewith): cyclohexane/ethyl acetate=95/5), the elutriant that contains product steams and desolventizes, and gets colorless oil 3.7 g, productive rate 79.7%.The structure detection result of product:
1) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
1 HNMR（δ）：1.187~1.204?(2s,?12H),?2.084(s,3H),2.090~2.144?(m,?2H),?2.709~2.747?(m,?2H),?2.846~2.914?(m,?2H),?4.181-4.212(m,2H),?7.143~7.249?(m,?3H)?。
2) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
13 CNMR（δ）：20.29,23.12,24.10,27.60,30.60,63.30,123.95,126.58,140.24,145.48,171.01,
171.46。
3) high resolution mass spectrum detects: mass spectrograph: the API3000 LC-Ms/Ms of American AB I company, ionization mode: EDI.
Ms + ：307.1917（C
18H
26O
6+H），329.1728（C
18H
26O
6+Na）。Collection of illustrative plates as shown in Figure 1.
The preparation of the acetic ester of Disoprofol butyric ester:
5 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 15 ml acetic anhydride, drip 3 ml triethylamines, stirring at room is reacted 3 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 4.84 g, productive rate 83.5%.
Embodiment 3
The preparation of the acetic ester of Disoprofol butyric ester:
5 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 15 ml acetic anhydride, drip 3 ml triethylamines, in 50 ℃ of stirring reaction 1 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 4.25 g, productive rate 73.3%.
The preparation of the acetic ester of Disoprofol butyric ester:
5 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 15 ml acetic anhydride, drip 3 ml triethylamines, in 95 ℃ of stirring reaction 30 min, be cooled to room temperature, reaction solution is poured in the 100 ml water, add 50 ml ethyl acetate, stir 10 min, standing demix is told organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 3.14 g, productive rate 54.1%.
Embodiment 5
The preparation of the propionic ester of Disoprofol butyric ester:
2 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 20 ml methylene dichloride, add 10 ml propionic anhydrides, be cooled to 0 ℃, drip 3 ml triethylamines, keep temperature stirring reaction 24 h, react and reaction solution is poured in the 100 ml water after complete, stir 10 min, standing demix is told organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure by column chromatography (elutriant: cyclohexane/ethyl acetate (v/v)=95/5) wash-out (following all herewith), after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.83 g, productive rate 75.4%.The structure detection result of product:
1) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
1 HNMR（δ）：1.153~1.205?(m,?15H),?2.098~2.167(m,2H),2.322~2.402?(m,?2H),?2.711~2.7478(m,?2H),?2.844~2.913?(m,?2H),?4.195-4.227(m,2H),?7.146~7.260?(m,?3H)?。
2) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
13 CNMR（δ）：?9.15,23.31,24.15,27.54,30.59,63.12,123.94,126.57,140.24,145.47,171.47,
174.42。
3) high resolution mass spectrum: mass spectrograph: the API3000 LC-Ms/Ms of American AB I company, ionization mode: EDI.
Ms + ：321.2065(C
19H
28O
4+H)，343.1886(C
19H
28O
4+Na)。Collection of illustrative plates as shown in Figure 2.
Embodiment 6
The preparation of the propionic ester of Disoprofol butyric ester:
2 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 10 ml propionic anhydrides, drip 3 ml triethylamines, stirring at room is reacted 3 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.89 g, productive rate 77.1%.
Embodiment 7
The preparation of the propionic ester of Disoprofol butyric ester:
2 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 10 ml propionic anhydrides, drip 3 ml triethylamines, in 50 ℃ of stirring reaction 1 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.77 g, productive rate 72.9%.
Embodiment 8
The preparation of the propionic ester of Disoprofol butyric ester:
2 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 10 ml propionic anhydrides, drip 3 ml triethylamines, in 95 ℃ of stirring reaction 30 min, be cooled to room temperature, reaction solution is poured in the 100 ml water, add 50 ml ethyl acetate, stir 10 min, standing demix is told organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.04 g, productive rate 43.1%.
Embodiment 9
The preparation of the acetic ester of Disoprofol hydroxyl valerate:
2 g Disoprofol 5-hydroxyl valerates are dissolved in 10 ml acetic anhydride, drip 3 ml triethylamines, stirring at room is reacted 3 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.72 g, productive rate 74.9%.The structure detection result of product:
1) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
1 HNMR（δ）：?1.190~1.202?(2s,?12H),?1.774~1.810(2m,4H),2.069?(s,?3H),?2.658~2.683?(m,?2H),?2.861~2.907?(m,?2H),?4.127~4.148(m,2H),7.150~7.258?(m,?3H)。
2) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
13 CNMR（δ）：20.97,20.99,21.59,27.56,28.16,33.64,63.94,123.92,126.51,140.25,145.50,
171.16,171.86。
3) high resolution mass spectrum: mass spectrograph: the API3000 LC-Ms/Ms of American AB I company, ionization mode: EDI.
Ms + ：321.2069(C
19H
28O
4+H)，343.1881(C
19H
28O
4+Na)。Collection of illustrative plates as shown in Figure 3.
The preparation of the propionic ester of Disoprofol hydroxyl valerate:
2 g Disoprofol 5-butyric esters are dissolved in 10 ml propionic anhydrides, drip 3 ml triethylamines, react 1 h in stirring at room, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, after the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.68 g, productive rate 69.9%.The structure detection result of product:
1) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
1 HNMR（δ）：?1.149~1.199?(m,?15H),?1.674~1.887(2m,4H),2.340~2.363?(m,?2H),?2.670~2.680?(m,?2H),?2.884~2.894?(m,?2H),?4.097~4.157(m,2H),7.160~7.255?(m,?3H)。
2) nuclear magnetic resonance analyser: BRUKER 400M, with CDCl
3Be solvent, TMS is interior mark, and δ unit is ppm.
13 CNMR（δ）：9.15,21.61,22.78,27.56,28.20,33.65,63.75,123.90,126.50,140.24,145.50,
171.86,174.54。
3) high resolution mass spectrum: mass spectrograph: the API3000 LC-Ms/Ms of American AB I company, ionization mode: EDI.
Ms + ：335.2216(C
20H
30O
4+H)，357.2028(C
20H
30O
4+Na)。Collection of illustrative plates as shown in Figure 4.
Embodiment 11
The preparation of the propionic ester of Disoprofol butyric ester:
2 g Disoprofol 4 hydroxybutyric acid esters are dissolved in 10 ml propionic anhydrides, drip 3 ml pyridines, in 50 ℃ of stirring reaction 1 h, react and reaction solution is poured in the 100 ml water after complete, add 50 ml ethyl acetate, stir 10 min, standing demix, tell organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, the elutriant that contains product removes behind the solvent to get colorless oil 1.65 g, productive rate 67.9% under reduced pressure.
With the molten 20ml chloroform of 2 g Disoprofol 5-hydroxyl valerates, add 10 ml acetic anhydride, drip 3 ml triethylamines, stirring at room is reacted 3 h, reacts and reaction solution is poured in the 100 ml water after complete, adds 50 ml chloroforms, stir 10 min, standing demix is told organic layer, wash respectively organic layer once with saturated sodium carbonate solution and water, tell organic layer, concentrating under reduced pressure is by the column chromatography wash-out, and the elutriant that contains product removes solvent under reduced pressure, get colorless oil 1.71 g, productive rate 74.7%.
Embodiment 12
Respectively three parts of concentration of each parallel preparation be 30 mg/ml above-described embodiment 1 the Disoprofol butyric ester acetic ester, embodiment 5 the Disoprofol butyric ester propionic ester, embodiment 9 the Disoprofol hydroxyl valerate acetic ester and
4.The propionic ester solution of the Disoprofol hydroxyl valerate of embodiment 10, add the rabbit plasma that places in advance water bath (37 ℃), mix, under 37 ℃ of conditions respectively at 0 min, 1 min, 3 min, 5 min, 7 min, 10 min, 20 min, 30 min, 1 h, 2 h, get above-mentioned 100 μ l plasma containing drugs when 3 h and 4 h, the HPLC method is measured the concentration of actives Propofol, and the result shows the acetic ester of Disoprofol butyric ester, the propionic ester of Disoprofol butyric ester, the propionic ester of the acetic ester of Disoprofol hydroxyl valerate and Disoprofol hydroxyl valerate can be decomposed into rapidly the actives Disoprofol in blood plasma.The external rabbit plasma rate of decomposition curve of the ester compound of multi-form Disoprofol alcohol ester as shown in Figure 5
Embodiment 13
Heat stability test: each 0.5 g of propionic ester of Disoprofol hydroxyl valerate of acetic ester, embodiment 10 of Disoprofol hydroxyl valerate of propionic ester, embodiment 9 of Disoprofol butyric ester that gets acetic ester, the embodiment 5 of the Disoprofol butyric ester of Disoprofol butyric ester (reference substance 1), Disoprofol hydroxyl valerate (reference substance 2) and above-described embodiment 1, in the clean container of opening, 60 ℃ of lower placements 10 days, respectively at the 5th day and sampling in the tenth day, detect each compounds content.Experimental result shows, the good thermal stability of the propionic ester of the acetic ester of the propionic ester of the acetic ester of Disoprofol butyric ester, Disoprofol butyric ester, Disoprofol hydroxyl valerate, Disoprofol hydroxyl valerate, and do not have Disoprofol butyric ester, Disoprofol hydroxyl valerate thermally-stabilised relatively poor of esterification.The result is as shown in table 1.
The experiment of the phenol hydroxy acid ester substituted ester compound thermostability of table 1 (60 ℃
)
| Compound (content wt%) | The 5th day content | The tenth day content |
| Reference substance 1(96%) | 43% | 21% |
| Reference substance 2(96%) | 64% | 40% |
| Embodiment 1(98%) | 96% | 95% |
| Embodiment 5(98%) | 97% | 95% |
| Embodiment 9(98%) | 97% | 96% |
| Embodiment 10(98%) | 98% | 98% |
Claims (4)
1. with the Disoprofol alcohol ester compounds of ester structure end, structure shown in formula I,
（Ⅰ）
Y in the formula is C
1 ~ 4The straight chain carbochain, R is ethanoyl or propionyl.
2. compound as claimed in claim 1, the Y that it is characterized in that said formula I structure is saturated carbon chains.
3. compound as claimed in claim 2 is characterized in that the Y of said formula I structure is-CH
2-CH
2-or-CH
2-CH
2-CH
2-.
4. the application of the compound of the described formula I structure of one of claims 1 to 3 in the maincenter suppressive drug preparation that the animal or human is produced tranquilizing soporific and/or anesthetic action as approach outside vein or vein.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110263939 CN102381972B (en) | 2011-09-08 | 2011-09-08 | Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110263939 CN102381972B (en) | 2011-09-08 | 2011-09-08 | Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102381972A CN102381972A (en) | 2012-03-21 |
| CN102381972B true CN102381972B (en) | 2013-10-30 |
Family
ID=45821868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110263939 Active CN102381972B (en) | 2011-09-08 | 2011-09-08 | Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102381972B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108164419B (en) * | 2017-12-25 | 2021-03-16 | 武汉大学 | Preparation and application of monodisperse polyethylene glycol monomethyl ether modified propofol prodrug |
| CN114105808A (en) * | 2021-11-19 | 2022-03-01 | 深圳市爱卫德为生物科技有限公司 | Propofol compound and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101633671A (en) * | 2009-07-13 | 2010-01-27 | 杭州奥默医药技术有限公司 | Phosphoryl carboxylic acid propofol ester derivative and preparation method thereof |
| CN101885735A (en) * | 2010-06-23 | 2010-11-17 | 四川大学华西医院 | Phenol hydroxy acid ester substituted phosphate compound, preparation method and application in medicines |
| CN101906039A (en) * | 2010-06-23 | 2010-12-08 | 四川大学华西医院 | Hydroxyl acid ester compound of substituted phenol, preparation method and application in drug |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA200504940B (en) * | 2003-01-28 | 2006-09-27 | Xenoport Inc | Amino acid derived prodrugs of propofol, compositions and uses thereof |
-
2011
- 2011-09-08 CN CN 201110263939 patent/CN102381972B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101633671A (en) * | 2009-07-13 | 2010-01-27 | 杭州奥默医药技术有限公司 | Phosphoryl carboxylic acid propofol ester derivative and preparation method thereof |
| CN101885735A (en) * | 2010-06-23 | 2010-11-17 | 四川大学华西医院 | Phenol hydroxy acid ester substituted phosphate compound, preparation method and application in medicines |
| CN101906039A (en) * | 2010-06-23 | 2010-12-08 | 四川大学华西医院 | Hydroxyl acid ester compound of substituted phenol, preparation method and application in drug |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102381972A (en) | 2012-03-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2877122C (en) | Preparation, uses and solid forms of obeticholic acid | |
| JP2019513422A (en) | Biosynthesis of cannabinoid prodrugs | |
| JP5856156B2 (en) | Hydroxy acid ester compound containing substituted phenol, process for producing the same, and central inhibitor using the same | |
| WO2017175064A1 (en) | Bioenzymatic synthesis of tetrahydrocannabivarin (thc-v), cannabinol (cbn), and cannabivarin (cbv) and their use as therapeutic agents | |
| Zhou et al. | Semi-synthesis and anti-tumor activity of 5, 8-O-dimethyl acylshikonin derivatives | |
| BRPI0711228A2 (en) | "compound, method of treating a mammal suffering from a disease or condition involving the enzymes cyclooxygenase, pharmaceutical composition, process for and deuteration of a compound for the exchange of at least one hydrogen atom of said compound with an atom of deuterium and process for prepare m compound " | |
| CA3168491A1 (en) | Cannabinoid derivatives | |
| Kazakova et al. | The synthesis and anti-inflammatory activity of quinopimaric acid derivatives | |
| CA3009149A1 (en) | Polymorphic crystalline forms of obeticholic acid | |
| CN111662294A (en) | Compound with activity of degrading Btk | |
| CN102381972B (en) | Propofol hydroxy acid ester compound with ester constitutional terminal, preparation method for same and application thereof | |
| Hua et al. | Syntheses and bioactivities of tricyclic pyrones | |
| CN105622558B (en) | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application | |
| JP2014534208A (en) | Polymorphs of CDDO acetate and uses thereof | |
| EP3252039B1 (en) | Compound containing indoleacetic acid core structure and use thereof | |
| JP2024509820A (en) | Synergistic cannabinoid esters, their salts and their uses | |
| CN111592520B (en) | 4, 5-disubstituted piperine derivatives, and preparation method and application thereof | |
| US7842721B2 (en) | Composition for treating cancer cells and synthetic method for the same | |
| EP2922834B1 (en) | 1-(dimethylamino)ethyl-substituted 6h-benzo[c]chromen-6-ones against senile dementia | |
| JP2754644B2 (en) | New lignans and 5-lipoxygenase inhibitors and aldose reductase inhibitors containing lignans as active ingredients | |
| CN102381997A (en) | Propofol hydroxy acid ester compound with amino-acid ester constitutional terminal, preparation method for same and application thereof | |
| Zhao et al. | Synthesis of azo derivatives of 4-aminosalicylic acid | |
| JP6205009B2 (en) | Method for producing phosphonocrotonic acid derivative | |
| JP6338276B2 (en) | Anticancer drug | |
| CN112824426B (en) | Allopregnanolone phosphonamide derivative, preparation method and medical application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |