CN103333084A - 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof - Google Patents
3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof Download PDFInfo
- Publication number
- CN103333084A CN103333084A CN2013102324585A CN201310232458A CN103333084A CN 103333084 A CN103333084 A CN 103333084A CN 2013102324585 A CN2013102324585 A CN 2013102324585A CN 201310232458 A CN201310232458 A CN 201310232458A CN 103333084 A CN103333084 A CN 103333084A
- Authority
- CN
- China
- Prior art keywords
- azo
- phenylformic acid
- butyryl
- butyryl acyloxy
- acid
- 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.)
- Granted
Links
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses 3,3'-azobis[6-(butanoyloxy)benzoic acid] and a preparation method and application thereof. The method comprises the following steps of: synthesizing a symmetric compound 1,3-dibutanoyloxy-2-carbonyl propane by taking 1,3-dihydroxy acetone as a synthesis raw material, and reducing the 1,3-dibutanoyloxy-2-carbonyl propane into dibutyrate 1,3-dibutanoyloxy-2-carbonyl propane; and carrying out an ester condensation reaction between dibutyrate 1,3-dibutanoyloxy-2-carbonyl propane and 1,3-dibutanoyloxy-2-carbonyl propane in the presence of EDCI serving as a dehydrating agent and DMAP serving as a catalyst to generate the target compound 3,3'-azobis[6-(butanoyloxy)benzoic acid]. After being orally taken into colon, 3,3'-azobis[6-(butanoyloxy)benzoic acid] is decomposed to release 5-aminosalicylic acid which acts together with butyric acid on the colon focus to realize a treatment effect.
Description
Technical field
The invention belongs to the medicament for resisting ulcerative colitis technical field, relate to 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] and its preparation method and application.
Background technology
(ulcerative colitis is a kind of chronic nonspecific inflammation of mainly involving rectum, mucous membrane of colon UC) to ulcerative colitis, and clinical manifestation is mainly diarrhoea, stomachache, mucosanguineous feces etc.; Its pathological change is the tissue reaction of filling the air, and comprises that the non-opposite sex of holding such as ulceration, crypt abscess, polyangitis disease, goblet cell minimizing and all kinds cell infiltration show.Can take place with the various autoimmune disease, as erythema nodosum, sacroiliitis, ankylosing spondylitis, sclerosing cholangitis, autoimmune hemolytic anemia etc.Course of disease protracted course of disease reaches the more than ten years, even decades and the possibility of canceration is arranged.Its sickness rate is about 3～14.3/10 ten thousand in American-European countries, China over nearly 10 years case surpass 20,000.The epidemiologic data prompting, the sickness rate of UC has the trend that increases year by year at home and abroad.This disease cause and onset of disease mechanism is still very not clear and definite; Be difficult to cure, very easily recur; The course of disease is tediously long, has a strong impact on patient body Health and Living quality, is classified as one of modern difficult treatment by the World Health Organization.
Summary of the invention
It is a kind of 3 that the problem that the present invention solves is to provide, 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] and preparation method thereof and with for the preparation of the pharmaceutical use for the treatment of ulcerative colitis.
The present invention is achieved through the following technical solutions:
A kind of compound, this compound are 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid], and its structural formula is:
With butyryl oxide and 3,3 '-azo two (6-hydroxy-benzoic acid) is used the base catalysis esterification, generates 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid];
Perhaps with butyryl oxide and 3, two (6-hydroxy-benzoic acid) heating reflux reactions of 3 '-azo generate 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid].
Described base catalysis esterification may further comprise the steps:
3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in the anhydrous propanone, adds the butyryl oxide that is dissolved in anhydrous propanone, adds triethylamine again, stirring at room, and after fully reacting, the vacuum concentration solvent; Water and ethyl acetate extraction residue are got organic layer, use HCl, NaHCO respectively
3Washing is regulated pH to neutral, concentrates with anhydrous sodium sulfate drying; With residue dissolving and be splined on silicagel column, carry out wash-out with the mixed solution of sherwood oil and ethyl acetate as elutriant, collect product, steam desolventize after, get 3,3 '-azo pair [6-(butyryl acyloxy) phenylformic acid].
Described sherwood oil is to mix according to the volume ratio of 10:1～5 to obtain elutriant with ethyl acetate.
Described heating reflux reaction may further comprise the steps:
With 3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in butyryl oxide, is heated to 81～82 ℃ of back flow reaction, fully after the reaction, uses petroleum ether, filters, and gets 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid].
3, the application of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] in the preparation medicament for resisting ulcerative colitis.
Described medicament for resisting ulcerative colitis is for lowering the medicine of mucosa injury exponential sum disease activity index.
Described medicament for resisting ulcerative colitis is for reducing the medicine of intestinal tissue MPO level.
Compared with prior art, the present invention has following beneficial technical effects:
Provided by the invention 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA), be that the collaborative prodrug of 5-aminosalicylic acid and butyric acid is with treatment UC, when it is oral enter colon after, be decomposed into 5-aminosalicylic acid and butyric acid, the two acting in conjunction is in colon lesions position performance therapeutic action then.
Provided by the invention 3, the preparation method of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is with 1, the 3-otan becomes ester synthetic compound 1 with butyryl oxide, 3-two butyryl acyloxies-2-carbonyl propane generate 1,3-, two butyryl acyloxies-2-hydroxy propane with its reduction again; Adopt EDCI as dewatering agent, DMAP is as catalyzer, with dibutyrate 1, and 3-two butyryl acyloxies-2-hydroxy propane and 1,3-, two butyryl acyloxies-2-hydroxy propane generation ester condensation reaction, synthesising target compound.Its synthetic route is simple, the productive rate height.
Provided by the invention 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] should can effectively lower mouse mucosa injury exponential sum and improve the DAI degree in the preparation of medicament for resisting ulcerative colitis, reduces intestinal tissue MPO level.Compare with Sodium propanecarboxylate mixture control group with using 5-aminosalicylic acid, all be better than 5-aminosalicylic acid and Sodium propanecarboxylate mixture control group in a plurality of detection indexs and DAI index.
Description of drawings
Fig. 1 is 3, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the figure that influences of mouse body weight change;
Fig. 2 is 3, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the figure that influences of mouse DAI index variation;
Fig. 3 is 3, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the figure that influences of the heavy index of mouse intestines;
Fig. 4 is 3, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the figure that influences of mouse colonic mucosal injury index;
Fig. 5 is 3, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the figure that influences of the MPO of mouse colon activity.
Embodiment
The invention provides the collaborative prodrug 3 of 5-aminosalicylic acid and butyric acid, 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) and the effect of preparation and resistive connection enteritis.The present invention is described in further detail below in conjunction with specific embodiment, and the explanation of the invention is not limited.
Adopt 3,3 '-azo two (6-hydroxy-benzoic acid) is carrier, is combined with ester bond with butyric acid, makes up collaborative prodrug treatment UC, in the hope of realizing Synergistic treatment UC.Adopt two kinds of synthesis technique synthesising target compounds 3 respectively, 3 '-azo two [6-(butyryl acyloxy) phenylformic acid].Behind synthesising target compound, determine the target compound structure by Fourier's infrared analysis, nucleus magnetic hydrogen spectrum analysis and mass spectrum; Investigate the effect of the anti-mouse experiment colitis of OLZ-BA on this basis.
1,3, (OLZ-BA) synthetic of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid]
3, two [6-(butyryl acyloxy) phenylformic acid] synthetic routes of 3 '-azo:
Synthetic route one:
Synthetic route two:
1.13, synthetic (route one) of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid]:
1g(0.0033mol) 3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in the 20mL anhydrous propanone, adds the 1.44g(0.0099mol that is dissolved in the 10mL anhydrous propanone in this heterogeneous solution) butyryl oxide, be added dropwise to the 2.0mL triethylamine, stirring at room.The detection reaction progress, until 3,3 '-azo two (6-hydroxy-benzoic acid) reacts completely the vacuum concentration solvent.Water and ethyl acetate extraction residue are got organic layer, use 1mol/LHCl, 1mol/LNaHCO respectively
3Washing is regulated pH to neutral, concentrates with anhydrous sodium sulfate drying, gets colorless oil.With residue dissolving and be splined on silicagel column, sherwood oil: ethyl acetate (10:1) is as eluent, and the ethyl acetate ratio increases progressively.Collect product, solvent evaporated under reduced pressure gets 3, and two [6-(butyryl acyloxy) phenylformic acid] 0.8g of 3 '-azo are the safran pulverulent solids; Productive rate is 54.4%.Its fusing point is 216.0 ℃.
1.23, synthetic (route two) of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid]:
7.0g(23mmol) 3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in 36.4g(0.23mol) butyryl oxide 81-82 ℃ backflow.The monitoring reaction progress, until 3,3 '-azo two (6-hydroxy-benzoic acid) reacts completely, and uses petroleum ether, filters, and gets 3, and two [6-(butyryl acyloxy) phenylformic acid] 9.0g of 3 '-azo are the safran pulverulent solids; Productive rate is 95.7%.Its fusing point is 216.0 ℃.
Qualitative identification: at sherwood oil: ethyl acetate: triethylamine=2mL: 1mL: under 1 the development system, the silica GF254 fluorescent plate shows a spot under the 253.7nm ultraviolet wavelength, and fluorescence is arranged, and the Rf value is 0.67.
The comparison of two kinds of synthetic methods:
Synthetic route one: adopt the base catalysis esterification, be reflected at normal temperature and carry out, condition is easy to control.But product is more difficult, needs pickling, alkali cleaning, and need column chromatography for separation to purify, reduced productive rate.
Synthetic route two: adopt the heating in water bath for reaction raw material to 81-82 ℃, stir 2h and get final product; Aftertreatment is comparatively convenient, need not column chromatography for separation and purifies, and productive rate is higher.
1.33, the structure elucidation of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid]:
1) 3, two [6-(butyryl acyloxy) phenylformic acid] the Fourier's infrared spectras of 3 '-azo
At 2974.03cm
-1, 2665.44cm
-1, 2352.99cm
-1Be ν CH on the butyryl radicals
3-, ν-CH
2-, ν-CH
2-absorption peak; At 3458.13cm
-1, 1755.10cm
-1Absorption peak for ester bond C=O key; At 1143.71cm
-1The asymmetrical stretching vibration peak of ester bond C-O-C is so proof has ester bond to generate; At 1294.15cm
-1, 1228.57cm
-1Charateristic avsorption band for phenyl ring.
2) 3, two [6-(butyryl acyloxy) phenylformic acid] proton nmr spectras of 3 '-azo
Proton nmr spectra (DMSO) ownership is as follows:
(t 3H) is three hydrogen on the butyryl radicals α C to δ 0.8828; 1.0026 (t 3H) is two hydrogen on another butyryl radicals α C; (m 2H) is two hydrogen on the butyryl radicals β C to δ 1.5287; (m 2H) is two hydrogen on another butyryl radicals β C to δ 1.6844; (t 2H) is two hydrogen on the butyryl radicals γ C to δ 2.1590; (t 2H) is two hydrogen on another butyryl radicals γ C to δ 2.6027; (d, 2H), (d, 2H), (s 2H) is the benzene ring hydrogen to δ 8.4267 to δ 8.2097 to δ 7.4672.
3) 3, two [6-(butyryl acyloxy) phenylformic acid] mass spectrums of 3 '-azo
m/z443.1
In sum, the gained compound is 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid].
Said synthesis route is simple, the productive rate height.
Below, select mouse TNBS colitis model acute to the mankind and that the reactivity ulcerative colitis is similar for use, further specify 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) for the therapeutic action of ulcerative colitis.
2,3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is (OLZ-BA) to the therapeutic action of mouse TNBS colitis
2.1 the foundation of mouse TNBS colitis model
The mouse experiment chamber is conventional raises, and 48 mouse are divided into 4 groups immediately, 12 every group., weigh and record successively each group mouse label respectively with picric acid.Fasting 12h before the modeling freely drinks water.With the mouse of fasting 12h with the slight little anesthesia of ether, insert the mouse colonic with blunt nosed filling stomach pin per anum, head end is apart from about the about 4cm of anus, slowly inject volume fraction and be the 50% ethanolic soln 0.1ml of 2.5% TNBS, after keeping mouse to be inverted a downward posture 30s, put back to normal raising the in the cage; Normal control group mouse gives normal saline enema.Begin administration behind the modeling 24h.
2.2 experiment grouping and observation index
Normal control group, model control group, 5-aminosalicylic acid and Sodium propanecarboxylate mixture (5-ASA+BA) control group and 3 are established in experiment, and 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) is organized, gastric infusion, and be administered once every day, successive administration 5 days.Normal and model control group all gives 0.5% the CMC-Na aqueous solution of equivalent.5-aminosalicylic acid and Sodium propanecarboxylate mixture (5-ASA+BA) control group dosage are [100mg (5-ASA)+40mg (Sodium propanecarboxylate)] kg
-13,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is dosage 240mgkg (OLZ-BA)
-1After modeling the 6th day, the mouse anesthesia of fasting 12h to be put to death, back of the body position is fixing.Mouse is cut belly open, takes out total colectomy.Vertically cut off colon along mesentery, rinse out intestinal contents with cold saline, the situation of visual inspection colonic mucosal injury.
Colonic mucosal injury index standards of grading: 0 minute: not damaged; 1 minute: no ulcer, contrafluxion; 2 minutes: ulcer is arranged; 3 minutes: only a position existed ulcer and inflammation; 4 minutes: two a plurality of positions existed ulcer and inflammation; 5 minutes: ulcer surpassed 2cm.
Measure total colectomy length and weigh the heavy index (total colectomy weight/total colectomy length) of calculating intestines.Get one in colonic pathological change position tissue, MPO, SOD and GSH-PX activity and MDA and GSH content are measured in-20 ℃ of preservations, measure and are all undertaken by the testing cassete method.
Other observation index: 1) statistics is respectively organized the dead mouse situation; 2) observe the mouse body weight change; 3) observe the mouse disease activity index (Disease activity index, DAI), the DAI standards of grading see Table 1; Wherein stool in mice is occulted blood to measure and is adopted adjacent first benzidine method, and criterion sees Table 2.
Table 1 mouse DAI standards of grading
The adjacent first benzidine method of table 2 is measured the ight soil result of determination of occulting blood
| The result | Phenomenon |
| Normally | Still do not develop the color after adding reagent 2min |
| Occult blood+ | After adding reagent 10s, just show light blue, become blue gradually |
| Occult blood ++ | After adding reagent, just show light blue, turn blue brown gradually |
| Occult blood +++ | Show blue brown immediately after adding reagent |
[0066] MPO determination of activity: adopt the dianisidine method.Get mouse colon and weigh, add the pH7.0PBS of 9 times of volumes, 4 ℃ of homogenate 30s, the centrifugal 30min of 12000rpm abandons supernatant liquor, takes off the HTAB solution of layer tissue 50mg adding 0.5%, 4 ℃ of homogenate 30s, the centrifugal 15min of 12000rpm condition.Get supernatant liquor 0.1m, add ODD solution 2.9ml, mixing in 460nm METHOD FOR CONTINUOUS DETERMINATION 3min, calculates per minute absorbancy changing value fast.Being defined in the amount that per minute under 25 ℃ of conditions decomposes 1 micromole's superoxide is a unit of enzyme activity.
The enzymic activity of 100 μ l sample tissue units is:
Annotate: 1molL
-1H
2O
2Absorbancy to change be 1.13 * 10
4So according to definition, 1 MPO of unit is 1 μ molL
-1H
2O
2Absorbance, be 1.13 * 10
-2
2.3 statistical analysis
Experimental data is with means standard deviation
Expression, statistical method adopts the t check analysis.There is statistical significance P＜0.05 for difference.
2.4 experimental result
1) to the influence of mouse survival condition: 12 of normal control groups, 7 of TNBS groups, 6 of 5-aminosalicylic acid and Sodium propanecarboxylate mixture (5-ASA+BA) control groups, 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) is organized 8.
2) to the influence of mouse body weight change: each organizes mouse body weight change result as described in Figure 1.Mouse weight loss after the modeling, body weight is gone up gradually after the pharmacological agent.3, it is the most obvious that 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) is organized the mouse weight recovery.
3) to the influence of mouse DAI index: mouse all bloody stool, just rare can occur after the TNBS modeling behind 24h, and movable, feed reduces situations such as weight loss.Each DAI index variation of organizing mouse as shown in Figure 2, TNBS group mouse DAI index obviously raises, modeling is basicly stable after 3 days, the DAI index significantly reduces behind the drug treatment, 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) is better than 5-aminosalicylic acid and Sodium propanecarboxylate mixture (5-ASA+BA) control group to the influence of DAI index.
4) to the heavily influence of exponential sum colonic mucosal injury index of mouse intestines
The mouse colon mucous hyperemia oedema occurs after the TNBS bowel lavage is handled, the intestines wall thickening, and there are necrosis and ulceration in the surface, compares with normal group, and the mucosa injury index of TNBS group significantly increases (P＜0.01) and shows that the foundation of mouse ulcerative colitis model is good; Compare with TNBS group, 3, the mucosa injury index that 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) is organized significantly descend (P＜0.01).The saturating wall damage of colon necrosis appears in the part mouse, and there be hardening, distortion or narrow in various degree in enteron aisle.The colon contraction in length, the heavy index of its intestines significantly increases (P＜0.01), compares all decline (P＜0.01) to some extent of the heavy index of the mouse intestines of administration group with the TNBS group.Experimental result as shown in Figure 3, Figure 4.
Among Fig. 3, compare ##P＜0.01 with the normal control group; Compare * * P＜0.01 with the modeling group; Compare Δ P＜0.05 with 5-ASA with BA mixing group;
Among Fig. 4, compare ##P＜0.01 with the normal control group; Compare * * P＜0.01 with the modeling group; Compare Δ P＜0.05 with 5-ASA with BA mixing group;
5) to the influence of MPO activity in the mouse colon
The mouse colon obviously raises because MPO in the colons such as inflammation, oedema, ulceration is active after the TNBS bowel lavage is handled.Compare active significantly increase (P＜0.01) of MPO in the TNBS group mouse colon with normal group; Compare with TNBS group, 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) organize the active significantly decline (P＜0.01) of MPO in the mouse colon.Experimental result as shown in Figure 5.
Among Fig. 5, compare ##P＜0.01 with the normal control group; Compare * * P＜0.01 with the modeling group; Compare Δ Δ P＜0.01 with 5-ASA with BA mixing group.
To sum up, experimental result shows, provide 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid] (OLZ-BA) can effectively lower rat mucosa injury exponential sum and improve the DAI degree, reduces the MPO of colon level.
Claims (8)
1. a compound is characterized in that, this compound is 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid], and its structural formula is:
2. compound 3, and the preparation method of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is characterized in that, comprises following operation:
With butyryl oxide and 3,3 '-azo two (6-hydroxy-benzoic acid) is used the base catalysis esterification, generates 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid];
Perhaps with butyryl oxide and 3, two (6-hydroxy-benzoic acid) heating reflux reactions of 3 '-azo generate 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid].
3. compound 3 as claimed in claim 2, the preparation method of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is characterized in that described base catalysis esterification may further comprise the steps:
3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in the anhydrous propanone, adds the butyryl oxide that is dissolved in anhydrous propanone, adds triethylamine again, stirring at room, and after fully reacting, the vacuum concentration solvent; Water and ethyl acetate extraction residue are got organic layer, use HCl, NaHCO respectively
3Washing is regulated pH to neutral, concentrates with anhydrous sodium sulfate drying; With residue dissolving and be splined on silicagel column, carry out wash-out with the mixed solution of sherwood oil and ethyl acetate as elutriant, collect product, steam desolventize after, get 3,3 '-azo pair [6-(butyryl acyloxy) phenylformic acid].
4. compound 3 as claimed in claim 3, the preparation method of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is characterized in that described sherwood oil is to mix according to the volume ratio of 10:1～5 to obtain elutriant with ethyl acetate.
5. compound 3 as claimed in claim 2, the preparation method of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] is characterized in that described heating reflux reaction may further comprise the steps:
With 3,3 '-azo two (6-hydroxy-benzoic acid) is dissolved in butyryl oxide, is heated to 81～82 ℃ of back flow reaction, fully after the reaction, uses petroleum ether, filters, and gets 3,3 '-azo two [6-(butyryl acyloxy) phenylformic acid].
6.3, the application of 3 '-azo two [6-(butyryl acyloxy) phenylformic acid] in the preparation medicament for resisting ulcerative colitis.
7. as application as described in the claim 6, it is characterized in that described medicament for resisting ulcerative colitis is for lowering the medicine of mucosa injury exponential sum disease activity index.
8. as application as described in the claim 6, it is characterized in that described medicament for resisting ulcerative colitis is for reducing the medicine of intestinal tissue MPO level.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310232458.5A CN103333084B (en) | 2013-06-09 | 2013-06-09 | 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310232458.5A CN103333084B (en) | 2013-06-09 | 2013-06-09 | 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103333084A true CN103333084A (en) | 2013-10-02 |
| CN103333084B CN103333084B (en) | 2015-01-07 |
Family
ID=49241310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310232458.5A Active CN103333084B (en) | 2013-06-09 | 2013-06-09 | 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103333084B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101610670A (en) * | 2006-11-03 | 2009-12-23 | 萨利克斯药品公司 | The preparation and the purposes of 2-hydroxyl-5-phenylazobenzoic acid derivatives |
-
2013
- 2013-06-09 CN CN201310232458.5A patent/CN103333084B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101610670A (en) * | 2006-11-03 | 2009-12-23 | 萨利克斯药品公司 | The preparation and the purposes of 2-hydroxyl-5-phenylazobenzoic acid derivatives |
Non-Patent Citations (2)
| Title |
|---|
| SIGAL SAPHIER, ET AL.: "Bacterial Reduction as Means for Colonic Drug Delivery: Can Other Chemical Groups Provide an Alternative to the Azo Bond?", 《J. MED. CHEM.》, vol. 55, 19 November 2012 (2012-11-19), pages 10781 - 10785 * |
| 赖俊英: "偶氮类结肠靶向高分子药物的合成、生物降解和释药性能的研究", 《中国优秀博硕士学位论文全文数据库（博士） 工程科技I辑》, no. 07, 15 July 2006 (2006-07-15), pages 016 - 20 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103333084B (en) | 2015-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022089845A (en) | Medicament having action on anti-inflammatory bowel diseases, and preparation method therefor and applications thereof | |
| CN109912600A (en) | It is a kind of prevent and treat pulmonary fibrosis imidazopyrimidine analog derivative and its application | |
| CN108147951B (en) | Phenyl alkene compound and preparation method and application thereof | |
| CN107382796A (en) | A kind of series antineoplastic medicaments of CA 4, synthetic method and its application | |
| Luo et al. | Mechanism of Paeoniae Radix Alba in the treatment of non-alcoholic fatty liver disease based on sequential metabolites identification approach, network pharmacology, and binding affinity measurement | |
| Zhang et al. | Sequential self-assembly and disassembly of curcumin hydrogel effectively alleviates inflammatory bowel disease | |
| CN103333084A (en) | 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof | |
| CN103483220A (en) | Compound, preparation method thereof and applications of compound in prevention of ulcerative colitis | |
| CN102643316B (en) | A kind of acylated glycosides compound and its preparation method and application | |
| CN101182298B (en) | Compound 2-hydroxy-5-butyrylamino benzoic acid and uses thereof | |
| CN103483214A (en) | Compound, preparation method thereof and applications of compound in prevention of ulcerative colitis | |
| CN105198714B (en) | Red bayberry 01 derivatives and its preparation method and application | |
| CN105295007B (en) | One kind conjugation water-soluble polymer tracer material and preparation method thereof | |
| CN104095856B (en) | The application in preparing anti-acute renal failure medicine of the diethylamine derivative of Cleistanone Cleistanone | |
| CN105949146A (en) | Pleuromutilin-tizoxanide hybrid drug and preparation method thereof | |
| CN108203408B (en) | Pyrazole compound containing N-aryl sulfonate as well as synthesis and application thereof | |
| CN104434929B (en) | The application in preparing anti-acute renal failure medicine of O-(piperazinyl) ethyl derivative of Cleistanone | |
| CN103951760B (en) | A kind of Grateloupia filicina (Wulf.) oligosaccharides and its preparation method and application | |
| CN110105365B (en) | Quinoline derivative VCTb5 and application thereof in preparation of anti-cancer drugs | |
| CN102670574A (en) | Application of curcumin in preparing medicine for treating intestinal ischemia reperfusion injury | |
| CN114478493B (en) | Traceable 5-aminosalicylic acid derivative and preparation and application thereof | |
| CN112190571B (en) | Application of gastrodia tuber source derivative in preparing medicine for treating inflammatory bowel disease | |
| CN102488675B (en) | Applications of flavonoid compound used in preventing or curing of inflammatory diseases | |
| CN103113307B (en) | Benzimidazoles compound and application thereof | |
| CN103463642A (en) | Preparation and application of human serum albumin-ruthenium inorganic medicine compound |
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 | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 710075 No. two, No. 69, hi tech Zone, Shaanxi, Xi'an Patentee after: Shaanxi pharmaceutical holding group new drug technology development Co.,Ltd. Address before: 710075 No. two, No. 69, hi tech Zone, Shaanxi, Xi'an Patentee before: SHAANXI PHARMACEUTICAL DEVELOPMENT CENTER |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200910 Address after: Room 10101, unit 1, building 3, No. 69, Keji 2nd Road, hi tech Zone, Xi'an City, Shaanxi Province Patentee after: MEDICINE Research Institute OF SHAANXI PHARMACEUTICAL HOLDING COOPERATION Address before: 710075 No. two, No. 69, hi tech Zone, Shaanxi, Xi'an Patentee before: Shaanxi pharmaceutical holding group new drug technology development Co.,Ltd. |