CN1616474A - Acetamido glucose devicative of indomethacin and its synthetic method and use - Google Patents
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Abstract
The present invention relates to acetamido glucose derivatives of indomethacin and their synthesis process and use. The kinds of acetamido glucose derivatives of indomethacin prepared with indomethacin and acetamido glucose are 1-O-[1-(4-chloro-benzoyl)-5 -methoxy-2-methyl-3-indolyl-acetoxy]-2-acetylamino-2-deoxy-alpha-D-glucose and 6-O-[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-3-indolyl-acetoxy]-2-acetylamino-2-deoxy-alpha-D-glucose. The derivatives of the present invention has the activity of inhibiting mouse ear dropsy caused by croton oil and may be used in preparing antiphlogistic medicine.
Description
Technical field
The present invention relates to a kind of acetylglucosamine derivative and synthetic method and application of indomethacin.This derivative has physiologically active, can be used for preparing anti-inflammatory drug.
Background technology
Indomethacin is a kind of NSAID (non-steroidal anti-inflammatory drug), and treatment rheumatism, rheumatoid arthritis etc. are had significant curative effect.But the same with most other NSAID (non-steroidal anti-inflammatory drug) class medicines, indomethacin has stronger side effects such as gastrointestinal mucosa damage, and has problems such as bioavailability is lower.Once adopted several different methods to reduce its toxic side effect and raising bioavailability in recent years, the ester derivative of synthetic NSAID (non-steroidal anti-inflammatory drug) is one of them.Nearest Borowiecka etc. has synthesized the 2-bromo sugar derivative of the NSAID (non-steroidal anti-inflammatory drug) that comprises indomethacin, acetylsalicylic acid, diclofenac, and RainerK.Uhrig etc. have synthesized compound 1-O-acyl group-glucosyl group-Ibuprofen BP/EP.Prove that through preliminary pharmacological tests this analog derivative has higher target, toxic side effect significantly reduces.And bioavailability is improved, and this is because glycoconjugate can see through hemato encephalic barrier by the transhipment effect of some special sugared transferring enzyme.And when the treatment osteoarthritis, NSAID (non-steroidal anti-inflammatory drug) only can play the effect of analgesia and anti-inflammatory, and can not fundamentally suppress the cause of disease.
Summary of the invention
The ester derivative and the synthetic method thereof that the purpose of this invention is to provide a kind of indomethacin acetylglucosamine, and the ester derivative of indomethacin acetylglucosamine is used to prepare anti-inflammatory drug, it can overcome the above-mentioned shortcoming of NSAID (non-steroidal anti-inflammatory drug).
A kind of ester derivative of indomethacin acetylglucosamine is characterized in that its structural formula is:
Wherein R is
The time, be 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose; R is
The time, be 6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose.
The synthetic method of the acetylglucosamine derivative of above-mentioned indomethacin, it is characterized in that with the acetylglucosamine being raw material, make 2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose or 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose; Make 2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose or 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose respectively with indomethacin generation esterification, generate 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxidation-alpha-D-glucose or 1-O-benzyl-6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose; Make 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 3; 4; 6-three-O-benzyl-2-deoxidation-alpha-D-glucose or 1-O-benzyl-6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose and palladium carbon/hydrogen effect, make 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose or 6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose.
Above-mentioned indomethacin acetylglucosamine derivative is used to prepare anti-inflammatory drug.
Embodiment
The used reaction solvent of the present invention is an analytical reagent, and used sherwood oil boiling point is 60-90 ℃.Column chromatography silica gel (100-200 order) is homemade silica gel.TLC adopts Merk Silica gel 60 F
254Plate.Various peacekeeping two dimensional NMR (NMR) wave spectrums record with JEOL JNM-ECP 600 nuclear magnetic resonance spectrometers.In the reaction formula of specific embodiment,
Embodiment 1:1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose (hereinafter to be referred as compound 1) synthetic
Step 1: benzyl protection
Compound 3 compounds 4 compounds 5
Compound 6 compounds 7
1mmol acetylglucosamine (hereinafter to be referred as compound 3) is dissolved in 10mL N, in the dinethylformamide (hereinafter to be referred as DMF), behind the ice bath reaction 30min, add 6mmol benzyl bromine, after stirring 10min, add the tetrabutylammonium iodide of 9.3mmol barium oxide, 1.7mmol barium hydroxide octahydrate and catalytic amount.Ice bath reaction 5h, room temperature reaction spends the night.Add the dilution of 15mL methylene dichloride, help with diatomite to filter insolubles, filter cake with washed with dichloromethane for several times.With the filtrate evaporate to dryness, methylene dichloride dissolving after washing twice, anhydrous sodium sulfate drying, evaporate to dryness get 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose (hereinafter to be referred as compound 4) 376mg, yield 64.7%, white solid, R
f0.15 (chloroform: sherwood oil=6: 1).The feed ratio of described acetylglucosamine and benzyl bromine is 1: 2-15 (mol ratio); The described reaction times is 1-48h; Described temperature of reaction is 0-40 ℃.
Behind the mixed-liquor return reaction 30h with 5.16mmol compound 4,125mL hydrochloric acid soln (3mol/L) and 180mL tetrahydrofuran (THF), steam and remove tetrahydrofuran (THF), remainder water solution 150mL dichloromethane extraction.Organic phase is used saturated sodium bicarbonate solution and water washing successively, and behind anhydrous sodium sulfate drying, evaporate to dryness gets pale yellow oily matter 3,4,6-three-O-benzyl-2-deoxidation-D-glucosamine hydrochloride (hereinafter to be referred as compound 5).The described reaction times is 10-40h.
Compound 5 is dissolved in the 50mL pyridine, adds the 5mL diacetyl oxide, behind the stirring at room 24h, add the 300mL methylene dichloride, wash successively with 5% hydrochloric acid soln, saturated sodium bicarbonate, water successively.Steam behind the anhydrous sodium sulfate drying and desolventize.Products therefrom is 1-O-ethanoyl-2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose (hereinafter to be referred as compound 6).Described compound 5 is 1 with the feed ratio of diacetyl oxide: 2-30; The feed ratio of described pyridine and diacetyl oxide is 1.5-20: 1 (volume ratio).The described reaction times is 1-48h; Described temperature of reaction is 0-40 ℃.
Compound 6 is dissolved in the 100mL methyl alcohol, adds the catalytic amount sodium methylate, room temperature reaction 2h.After the TLC detection reaction finished, the solid that the adding methylene dichloride is separated out all dissolved, and adds Dowex H
+Resin neutralization reaction liquid is to neutral.The filtering resin, steaming desolventizes, and the gained solid gets 2-acetylaminohydroxyphenylarsonic acid 3,4 with ethyl alcohol recrystallization, 6-three-O-benzyl-2-deoxy-D-glucose (hereinafter to be referred as compound 7) 950mg, white solid.Mother liquor gets pale yellow solid 630mg through the silicagel column purifying.R
f(0.19 chloroform: methyl alcohol, 40: 1), three step yields 62.3%.The described reaction times is 0.5-12h; Described temperature of reaction is 0-40 ℃.
Step 2: esterification
Compound 7 compounds 8
1.76mmol compound 7,1.93mmol indomethacin are dissolved in the 60mL methylene dichloride, after ice bath stirred 30min down, with 2.11mmol N, the 4-methylamino pyridine of N-dicyclohexylcarbodiimide, catalytic amount added in the reaction flask, under ice bath behind the stirring reaction 1h, room temperature reaction.TLC follows the tracks of reaction process; after question response finishes; the filtering precipitation; the filtrate decompression distillation; silicagel column separate light yellow solid 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 3; 4,6-three-O-benzyl-2-deoxidation-alpha-D-glucose (hereinafter to be referred as compound 8) 1.09g, productive rate 74.7%.R
f(0.17 ethyl acetate/petroleum ether, 1: 1).The spectral data of compound 8:
1H-NMR (CDCl
3, 600MHz): δ 7.58 (d, 1H, J=8.5Hz, Ar-H), 7.36-7.26 (m, 13H, Ar-H), 7.22-7.21 (m, 2H, Ar-H), 7.15-7.14 (m, 2H, Ar-H), 7.01 (d, 1H, J=2.6Hz, Ar-H), 6.94 (d, 1H, J=8.8Hz, Ar-H), 6.69 (dd, 1H, J
1=2.6,8.8Hz, Ar-H), 6.07 (d, 1H, J=3.7Hz, H-1-α), 4.74 (d, 1H, J=10.6Hz, Ph-CH-), 4.70 (d, 1H, J=11.3Hz, Ph-CH-), 4.58 (d, 1H, J=12.1Hz, Ph-CH-), 4.56 (d, 1H, J=9.1Hz, N-H), 4.51 (d, 1H, J=11.0Hz, Ph-CH-), 4.46 (d, 1H, J=12.1Hz, Ph-CH-), 4.37 (d, 1H, J=11.4Hz, Ph-CH-), 4.28-4.24 (m, 1H, H-2), 3.74 (m, 1H, H-3), 3.71 (s, 3H ,-OCH
3), 3.69 (s, 2H ,-CH
2-), 3.66 (dd, 1H, J=3.7,11.0Hz, H-6), 3.59 (ddd, 1H, J
1=1.8,3.7,9.9Hz, H-5), 3.56 (dd, 1H, J=1.9,11.0Hz, H-6), 3.38 (dd, 1H, J=8.8,10.7Hz, H-4), 2.37 (s, 3H ,-CH
3), 1.48 (s, 3H ,-CH
3). described compound 7 is 1-2 with the feed ratio of indomethacin: 1-2; Described indomethacin and N, the feed ratio of N-dicyclohexylcarbodiimide is 1: 1.1-5; Used solvent is methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), dioxane, or the mixed solution of above-mentioned solvent.The described reaction times is 0.5-24h; Described temperature of reaction is 0-40 ℃.
Step 3: remove benzyl
Compound 8 compounds 1
1.31mmol compound 8 is dissolved in 100mL ethyl acetate/ethanol (1: 1), adds 0.1g palladium-carbon (10%), room temperature reaction spends the night under atmosphere of hydrogen.TLC follows the tracks of reaction to the reaction end, filtering palladium-carbon (diatomite helps filter).After the filtrate decompression distillation, silicagel column separate light yellow solid compound 1 (585mg, productive rate 79.5%).R
f(0.24 chloroform: methyl alcohol, 6: 1).The spectral data of compound 1:
1H-NMR (CD
3OD, 600MHz): δ 7.69-7.68 (m, 2H, Ar-H), 7.56-7.53 (m, 2H, Ar-H), 6.99 (d, 1H, J=2.6Hz, Ar-H), 6.90 (d, 1H, J=9.1Hz, Ar-H), 6.68 (dd, 1H, J=2.6,9.2Hz, Ar-H), 6.15 (d, 1H, J=3.7, H-1-α), 3.96 (dd, 1H, J=3.7,11.0Hz, H-2), 3.87 (d, 1H, J=15.8Hz ,-CH
2-), 3.80 (s, 3H ,-OCH
3), 3.76 (d, 1H, J=16.1Hz ,-CH
2-), 3.61 (dd, 1H, J=8.8,10.6Hz, H-3), 3.53 (dd, 1H, J=4.4,12.1Hz, H-6), 3.49 (dd, 1H, J=2.2,12.1Hz, H-6), 3.42 (t, 1H, J=8.8Hz, H-4), 3.27 (ddd, 1H, J=2.6,4.4,9.9Hz, H-5), 2.34 (s, 3H ,-CH
3), 1.90 (s, 3H ,-CH
3).
13CNMR (CD
3OD, 150MHz): δ 173.8,171.4, and 169.9,157.7,140.2,137.1,135.5,132.4,133.2,131.8,130.3,116.0,113.7,112.7,102.5,92.6,76.2,72.4,71.3,61.9,56.2,54.4,30.9,22.4,13.4.Used solvent is the mixed solution of methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), ethyl acetate, ethanol, methyl alcohol or above-mentioned solvent.The described reaction times is 0.5-24h; Described temperature of reaction is 0-50 ℃.
Embodiment 2:6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose (hereinafter to be referred as compound 2) synthetic
Step 1: benzyl protection
Compound 3 compounds 9
After the mixed solution of 0.01mol compound 3 and 20mL phenylcarbinol stirred, add the 0.1mL boron trifluoride diethyl etherate, reflux.The TLC detection reaction is chilled to 0 ℃ with reaction solution after finishing, and slowly adds the 120mL ether, has a large amount of precipitations to separate out.After 4 ℃ of standing over night, filter, filter cake washs with ether, gets white solid 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose (hereinafter to be referred as compound 9) 2.60g, yield 83.6%, R after the drying
f0.30 (chloroform: methyl alcohol=6: 1).When the charging capacity of compound 3 was 0.01mol, the charging capacity of described phenylcarbinol was 5-50ml, and the charging capacity of described boron trifluoride diethyl etherate is 0.05-0.3ml.The described reaction times is 1-24h.
Step 2: esterification
Compound 9 compounds 10
8mmol compound 9,8mmol indomethacin are dissolved in the mixed solution of 100mL tetrahydrofuran (THF) and 15mL dioxane, 0 ℃ adds 9.2mmolN, the 4-methylamino pyridine of N-dicyclohexylcarbodiimide and catalytic amount down.Behind the ice bath reaction 1h, room temperature reaction spends the night.TLC follows the tracks of reaction process; after question response finishes; the filtering precipitation; the filtrate decompression distillation; the silicagel column purifying gets white solid 1-O-benzyl-6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose (hereinafter to be referred as compound 10) 2.22g; productive rate 42.6%, R
f0.14 (chloroform: methyl alcohol=25: 1).The spectral data of compound 10:
1H-NMR (DMSO-d
6, 600MHz): δ 7.84 (d, 1H, J=8.4Hz, N-H), 7.62 (m, 4H, Ar-H), 7.32-7.25 (m, 5H, Ar-H), 7.06 (d, 1H, J=2.5Hz, Ar-H), 6.87 (d, 1H, J=8.8Hz, Ar-H), 6.70 (dd, 1H, J=2.6,9.2Hz, Ar-H), 5.30 (d, 1H, J=5.9Hz, 4-OH), 4.89 (d, 1H, J=5.5Hz, 3-OH), 4.66 (d, 1H, J=3.7Hz, H-1-α), 4.47 (d, 1H, J=12.5Hz, Ph-CH-), 4.37 (dd, 1H, J11.8,11.7Hz, H-6), 4.26 (d, 1H, J=12.5Hz, Ph-CH-), 4.12 (dd, 1H, J=6.6,12.1Hz, H-6), 3.81 (s, 2H ,-CH
2-), 3.74 (s, 3H ,-OCH
3), 3.71-3.66 (m, 2H, H-2, H-5), 3.54-3.50 (m, 1H, H-3), 3.19-3.15 (m, 1H, H-4), 2.32 (s, 3H ,-CH
3), 1.82 (s, 3H ,-CH
3). described compound 9 is 1-2 with the feed ratio of indomethacin: 1-2; Described indomethacin and N, the feed ratio of N-dicyclohexylcarbodiimide is 1: 1.1-5; Used solvent is the mixed solution of methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), dioxane or above-mentioned solvent.The described reaction times is 1-24h; Described temperature of reaction is 0-50 ℃.
Step 3: remove benzyl
Compound 10 compounds 2
1.29mmol compound 10 is dissolved in 60mL ethyl acetate/ethanol (1: 1), adds 0.2g palladium-carbon (10%), room temperature reaction under atmosphere of hydrogen.TLC follows the tracks of reaction to the reaction end, filtering palladium-carbon (diatomite helps filter).After the filtrate decompression distillation, the silicagel column purifying gets light yellow solid compound 2 (524mg, productive rate 72.4%), R
f0.31 (chloroform: methyl alcohol=8: 1).The spectral data of compound 2:
1H-NMR (CD
3OD, 600MHz): δ 7.68-7.65 (m, 2H, Ar-H), 7.56-7.52 (m, 2H, Ar-H), 7.00 (d, 1H, J=2.2Hz, Ar-H), 6.88 (d, 1H, J=9.1Hz, Ar-H), 6.63 (dd, 1H, J=2.6,9.2Hz, Ar-H), 5.07 (d, 1H, J=3.3Hz, H-1-α), 4.40 (dd, 1H, J=2.2,11.7Hz, H-6), 4.27 (dd, 1H, J=5.1,12.1Hz, H-6), 3.99 (ddd, 1H, J=2.2,5.1,10.3Hz, H-5), 3.82 (m, 1H, H-2), 3.80 (s, 3H ,-OCH
3), 3.76 (s, 2H ,-CH
2-), 3.69 (m, 1H, H-3), 3.15 (m, 1H, H-4), 2.29 (s, 3H ,-CH
3), 1.98 (s, 3H ,-CH
3).
13CNMR (CD
3OD, 150MHz): δ 173.7,173.0, and 171.2,157.3,137.1,133.9,132.4,132.0,130.6.130.2,130.0,115.9,113.9,112.6,102.4,92.6,72.6,72.5,70.7,65.4,56.2,55.8,30.6,22.6, the used solvent of 13.5. is the mixed solution of methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), ethyl acetate, ethanol, methyl alcohol or above-mentioned solvent.The described reaction times is 1-24h; Described temperature of reaction is 0-50 ℃.
The experiment of mouse knoting oil dropsy of ear
The acetylglucosamine derivative of two kinds of indomethacins of the present invention has been carried out the inhibiting pharmacological evaluation of mouse ear Oleum Tiglii inflammation.The mouse random packet, is divided into control group and sample sets by 10 every group.Sample suspends with 5% gumwater, after pressing 0.042mmol/kg filling helmet administration 1h, mouse left side ear is coated with 2% crotons fluid [V (Oleum Tiglii): V (ethanol): V (ether)=2: 20: 78], 50 μ L, and 4h post-tensioning neck is put to death, and cuts ears, stainless steel blunderbuss with diameter 8mm sweeps away left and right sides auricle, weigh respectively, with about two ear weight differences be the swelling degree, with control group relatively, calculate the ear swelling inhibiting rate, formula is as follows:
The pharmacological results shows that the acetylglucosamine derivative compound 1 of indomethacin of the present invention and compound 2 and ear swelling inhibiting rate are respectively 24.1%, 25.4%.The ear swelling inhibiting rate of indomethacin is 25.0%.
Claims (1)
1. the acetylglucosamine derivative of an indomethacin is characterized in that its structural formula is:
Wherein R is
The time, be 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose; R is
The time, be 6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose.
The synthetic method of the acetylglucosamine derivative of indomethacin as claimed in claim 1, it is characterized in that with the acetylglucosamine being raw material, make 2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose or 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose; Make 2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose or 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose respectively with indomethacin generation esterification, generate 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxidation-alpha-D-glucose or 1O-benzyl-6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose; Make 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 3; 4; 6-three-O-benzyl-2-deoxidation-alpha-D-glucose or 1-O-benzyl-6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose and palladium carbon-hydrogen effect, make 1-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose or 6-O-[1-(4-chloro-benzoyl)-5-methoxyl group-2-methyl-3-indoles-acetoxyl group]-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-alpha-D-glucose.
Synthetic method as claimed in claim 2, it is characterized in that described 2-acetylaminohydroxyphenylarsonic acid 3,4,6-three-O-benzyl-2-deoxy-D-glucose or 1-O-benzyl-2-acetylaminohydroxyphenylarsonic acid 2-deoxy-D-glucose is methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), dioxane with the solvent that indomethacin generation esterification is used respectively, or the mixed solution of above-mentioned solvent.
The acetylglucosamine derivative of the described indomethacin of claim 1 is used to prepare anti-inflammatory drug.
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| CN100460413C (en) * | 2006-01-16 | 2009-02-11 | 中国药科大学 | Chemical compound synthesized by carboxylic acid analog non-steroid anti-inflammatory agent and aminoglucose or its salt, and its synthesis method and uses |
| CN102391323A (en) * | 2011-10-18 | 2012-03-28 | 首都医科大学 | Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof |
| CN102391323B (en) * | 2011-10-18 | 2013-09-25 | 首都医科大学 | Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof |
| CN102977159A (en) * | 2012-11-18 | 2013-03-20 | 大连九信生物化工科技有限公司 | Preparation method of hydroxyl located on C 3 position of benzyl oxide protected D-glucosamine derivative |
| CN107459538A (en) * | 2016-06-03 | 2017-12-12 | 首都医科大学 | The acetyl lysylamino glucose of two indoles, 2 propane, 2 indoles 3, it is synthesized, activity and application |
| CN107459539A (en) * | 2016-06-03 | 2017-12-12 | 首都医科大学 | Glucosulfone -2- indole-3-acetamide -2- propane, it is synthesized, activity and application |
| CN107459539B (en) * | 2016-06-03 | 2020-09-01 | 首都医科大学 | Di-glucose-2-indole-3-acetamide-2-propane, synthesis, activity and application thereof |
| CN107459538B (en) * | 2016-06-03 | 2020-10-16 | 首都医科大学 | Diindole-2-propane-2-indole-3-acetyl lysyl glucosamine, synthesis, activity and application thereof |
| CN107513082A (en) * | 2016-06-17 | 2017-12-26 | 首都医科大学 | Glucosyl group indoleacetamide base heteroauxin carbomethoxy propane, it is synthesized, activity and application |
| CN107513081A (en) * | 2016-06-17 | 2017-12-26 | 首都医科大学 | The acetyl glutamy Glucosamine propane of 2,2 2 indoles 3, it is synthesized, anti-inflammatory activity and application |
| CN107513082B (en) * | 2016-06-17 | 2020-09-01 | 首都医科大学 | Glucosyl indole acetamido-indole acetic acid methyl ester propane, its synthesis, activity and application |
| CN107513081B (en) * | 2016-06-17 | 2020-09-01 | 首都医科大学 | 2, 2-diindole-3-acetylglutamylglucosyl-propane, its synthesis, anti-inflammatory activity and use |
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| CN1256342C (en) | 2006-05-17 |
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