CN104861002A - 3,6-anhydroglucose structure-containing phenyl C-glucoside derivatives and their preparation method and use - Google Patents
3,6-anhydroglucose structure-containing phenyl C-glucoside derivatives and their preparation method and use Download PDFInfo
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Abstract
The invention relates to the field of drugs related to diabetes. The invention relates to 3,6-anhydroglucose structure-containing phenyl C-glucoside structure sodium glucose cotransporter 2 (SGLT2) inhibitors, a preparation method of the inhibitors, a pharmaceutical composition containing the inhibitor and a use of the inhibitors in preparation of drugs for treating diabetes. R1 represents H, F, Cl, Br, I, C1-C3 alkyl, OR3 or SR4, R2 represents C1-C5 alkyl or OR5, and R3, R4 and R5 represent C1-C5 alkyl.
Description
Technical field
The present invention relates to the pharmaceutical field that diabetes are relevant.Specifically, the present invention relates to and contain 3 to diabetes are medicative, 2 type sodium glucose cotransporter (SGLT2) inhibitor of the phenyl C-glucoside structure of 6-anhydroglucose and preparation method thereof, and the pharmaceutical composition containing them.
Background technology
Whole world diabetic subject at present nearly about 1.7 hundred million, wherein about the overwhelming majority is II type (i.e. non-insulin-depending type) diabetic subject.N1,N1-Dimethylbiguanide class, sulfonylurea, insulin type, thiazolidinediones, alpha-glucosidase inhibitor class and dipeptidyl peptidase-iv inhibitor class medicine is mainly contained at present at the antidiabetic medicine of Clinical practice, these medicines have good therapeutic action, but there is safety issue in long-term treatment, as: liver toxicity, some drugs still has the problems such as body weight increase.
2 type sodium glucose cotransporter (SGLT2) are the novel targets of the treatment diabetes of discovered in recent years.SGLT2 is mainly distributed in renal proximal tubules, and its effect absorbs the glucose in urine, and returns it in blood, therefore suppresses that SGLT2's just can reduce the concentration of glucose in blood, and this method reduces glucose level from the past different approach.When SGLT2 function is obstructed, in urine, more glucose will be secreted, this glucose level that will contribute to diabetic subject and keep correct.Because SGLT2 inhibitor stays out of glucose metabolism, it can as the means of supplementing out economy of glycemic control main stream approach.
Chinese patent CN200610093189.9 discloses the compound of having structure as SGLT2 inhibitor:
Wherein, A is O, S, NH, (CH
2)
n, n=0-3.
Chinese patent CN200380110040.1 discloses the compound of having structure as SGLT2 inhibitor:
Wherein, A is covalent linkage, O, S, NH, (CH
2)
n, n=1-3.
Chinese patent CN200480006761.2 discloses the compound of having structure as SGLT2 inhibitor:
Wherein, X is covalent linkage or low-grade alkylidene.
The invention discloses a class containing the phenyl C-glucoside analog derivative of 3,6-anhydroglucose as novel SGLT2 inhibitor, these compounds can be used for preparing the medicine for the treatment of diabetes particularly diabetes B.
Summary of the invention
An object of the present invention is the shortcoming and defect overcoming prior art, provide one to have excellent activity, there is compound and the pharmaceutically acceptable prodrug ester thereof of general formula I.
Another object of the present invention is to provide preparation and has the compound of general formula I and the method for pharmaceutically acceptable prodrug ester thereof.
Another object of the present invention be to provide compound containing general formula I and pharmaceutically acceptable prodrug ester as effective constituent, and the medicinal compositions of one or more pharmaceutically acceptable carrier, vehicle or thinners, and the application in treatment diabetes.
Now in conjunction with object of the present invention, content of the present invention is specifically described.
The present invention has the compound of general formula (I) structure and pharmaceutically acceptable prodrug ester thereof, has following structure:
Wherein,
R
1be selected from H, F, Cl, Br, I, C
1-C
3alkyl, OR
3and SR
4;
R
2be selected from C
1-C
5alkyl and OR
5;
Wherein, R
3-R
5be selected from C
1-C
5alkyl.
Preferred following general formula (I) compound,
Wherein,
R
1be selected from F, Cl, Me, OMe and SMe;
R
2be selected from C
1-C
3alkyl and OR
5;
Wherein, R
5be selected from C
1-C
3alkyl.
More preferably the compound of general formula (I) has following structure,
General formula of the present invention (I) compound can be synthesized by following route:
Compound II per under the existence of organic bases with 1 equivalent about Tosyl chloride (TsCl) react, its 6-OH, by optionally tosylation, obtains compound III; Compound III heats and obtains Compound I in the ethanol water or methanol-water of NaOH.Wherein, R
1and R
2definition as previously mentioned.
General formula of the present invention (I) compound also can be synthesized by following route:
Compound II per is the synthesis of method disclosed in CN201310213608.8 IV conventionally; Compound IV under the existence of organic bases with 1 equivalent about Tosyl chloride (TsCl) react, its 6-OH, by optionally tosylation, obtains compound V; Compound V heats in the MeOH solution of MeONa, or heats in the aqueous ethanolic solution of NaOH or in methanol aqueous solution, can obtain I.Wherein, R
1and R
2definition as previously mentioned.
The pharmaceutically acceptable prodrug ester of formula I of the present invention, comprises the ester that any one or more hydroxyl in molecule and ethanoyl, pivaloyl group, various phosphoryl, formamyl, alkoxyl formyl etc. are formed.
Formula I of the present invention, can make pharmaceutical composition jointly with one or more pharmaceutically acceptable carrier, vehicle or thinner.This pharmaceutical composition can make the formulations such as solid orally ingestible, liquid oral medicine, injection.Described solid and liquid oral medicine comprise: tablet, dispersible tablet, sugar-coat agent, granule, dry powder doses, capsule and solution.Described injection comprises: little pin, infusion solutions, freeze-dried powder etc.
Composition of the present invention, described pharmacy or bromatology can accept auxiliary material and be selected from: weighting agent, disintegrating agent, lubricant, glidant, effervescent, correctives, sanitas, coating material or other vehicle.
Composition of the present invention, described pharmacy or bromatology can accept auxiliary material.Weighting agent is the composition of one or more that weighting agent comprises lactose, sucrose, dextrin, starch, pregelatinized Starch, N.F,USP MANNITOL, sorbyl alcohol, secondary calcium phosphate, calcium sulfate, calcium carbonate, Microcrystalline Cellulose; Described tackiness agent comprises the composition of one or more of sucrose, starch, polyvidone, Xylo-Mucine, hypromellose, hydroxypropylcellulose, methylcellulose gum, polyoxyethylene glycol, medicinal alcohol, water; Described disintegrating agent comprises the composition of one or more of starch, crosslinked polyvidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, carmethose, gas-producing disintegrant.
Compound of Formula I of the present invention has the restraining effect of SGLT2, can be used as the medicine of effective constituent for the preparation of diabetes aspect.The activity of compound of Formula I of the present invention is by glucose in urine modelling verification.
Compound of Formula I of the present invention is effective in quite wide dosage range.The dosage that such as every day takes, within the scope of 1mg-1000mg/ people, is divided into once or administration for several times.The actual dosage taking compound of Formula I of the present invention can be decided according to relevant situation by doctor.These situations comprise: the physical state of patient, route of administration, age, body weight, individual reaction to medicine, the severity etc. of symptom.
Embodiment
Below in conjunction with embodiment, the present invention is further illustrated.It should be noted that, following embodiment be only for illustration of, and not for limiting the present invention.The various changes that those skilled in the art's training centre according to the present invention is made all should within the protection domain required by the application's claim.
embodiment 1
1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1-deoxidation-3,6-dehydration-β-D-Glucopyranose (I-1)
A.
4.09g (10mmol) Compound II per-1 is dissolved in the methylene dichloride of 30mL drying, add 3.04g (30mmol) triethylamine, ice-water bath cooling is lower stirs, and then slowly drips the solution that methylene dichloride that 2.29g (12mmol) TsCl is dissolved in 5mL drying is made.Dropwise rear gained solution and slowly rise to room temperature, then at room temperature continue stirring 3 hours, now TLC display reaction completes.
Reaction mixture is poured in 200mL frozen water, stirs, with 100mL × 3 dichloromethane extraction.Merge organic phase, use saturated NaHCO successively
3solution and brine It, anhydrous sodium sulfate drying, boils off solvent on a rotary evaporator, and the resistates obtained, through column chromatography purification, obtains product III-1.White foam solid, productive rate 35%,
1h NMR (DMSO-d
6, 400MHz) δ: 7.71 (d, 2H, J=8.4Hz), 7.37 (d, 2H, J=8.0Hz), 7.35 (d, 2H, J=8.0Hz), 7.23 (d, 1H, J=2.0Hz), 7.07-7.12 (m, 3H), 6.81 (d, 2H, J=8.8Hz), 5.21 (d, 1H, J=5.6Hz), 5.03 (d, 1H, J=5.2Hz), 4.88 (d, 1H, J=5.6Hz), 4.23 (d, 1H, J=8.8Hz), 4.01-4.07 (m, 1H), 3.92-3.99 (m, 5H), 3.43-3.47 (m, 1H), 3.19-3.25 (m, 1H), 3.10-3.15 (m, 1H), 3.03-3.09 (m, 1H), 2.36 (s, 3H), 1.28 (t, 3H, J=7.0Hz).
B.
1.69g (3mmol) compound III-1 is dissolved in 15mL methyl alcohol, and stirred at ambient temperature then adds the NaOH solution of 1.5mL30%, then temperature rising reflux 3 hours, and now TLC display reaction completes.
Be poured in 200mL frozen water after reaction mixture cool to room temperature, stir, with 100mL × 3 dichloromethane extraction.Merge organic phase, with brine It, anhydrous sodium sulfate drying, boil off solvent on a rotary evaporator, the resistates obtained, through column chromatography purification, obtains product I-1.White foam solid, productive rate 75%,
1h NMR (DMSO-d
6, 400MHz) and δ: 7.36 (d, 1H, J=8.4Hz), 7.27 (d, 1H, J=2.0Hz), 7.21 (dd, 1H, J=2.0Hz and8.4Hz), 7.08 (d, 2H, J=8.4Hz), 6.83 (d, 2H, J=8.4Hz), 5.73 (d, 1H, J=3.2Hz, D
2o-exchangable), 5.06 (d, 1H, J=6.4Hz, D
2o-exchangable), 4.83 (d, 1H, J=8.4Hz), 4.17-4.20 (m, 2H), 3.93-4.01 (m, 4H), 3.78-3.81 (m, 2H), (3.61 d, 1H, J=9.6Hz), (3.46 t, 1H, J=7.2Hz), 1.29 (t, 3H, J=7.0Hz).
embodiment 2
1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1-deoxidation-3,6-dehydration-β-D-Glucopyranose (I-1)
A.
Compound II per-1 uses the synthesis of method disclosed in prior art CN201310213608.8 IV-1.
5.35g (10mmol) compound IV-1 is dissolved in the methylene dichloride of 30mL drying, add 3.04g (30mmol) triethylamine, ice-water bath cooling is lower stirs, and then slowly drips the solution that methylene dichloride that 2.29g (12mmol) TsCl is dissolved in 5mL drying is made.Dropwise rear gained solution and slowly rise to room temperature, then at room temperature continue stirring 3 hours, now TLC display reaction completes.
Reaction mixture is poured in 200mL frozen water, stirs, with 100mL × 3 dichloromethane extraction.Merge organic phase, use saturated NaHCO successively
3solution and brine It, anhydrous sodium sulfate drying, boils off solvent on a rotary evaporator, and the resistates obtained, through column chromatography purification, obtains product V-1.White solid, productive rate 85%, fusing point 140-141.5 DEG C,
1h NMR (DMSO-d
6, 400MHz) δ: 7.71 (d, 2H, J=8.0Hz), 7.40 (d, 1H, J=8.0Hz), 7.36 (d, 2H, J=8.4Hz), 7.16 (s, 1H), 7.13 (dd, 1H, J=1.8Hz and8.2Hz), 7.05 (d, 2H, J=8.4Hz), 6.81 (d, 2H, J=8.8Hz), 5.29 (t, 1H, J=9.4Hz), 4.99 (t, 1H, J=9.2Hz), 4.88 (t, 1H, J=9.8Hz), 4.60 (d, 1H, J=9.6Hz), 4.07-4.10 (m, 3H), 3.93-3.98 (m, 4H), 2.36 (s, 3H), 1.93 (s, 3H), 1.90 (s, 3H), 1.66 (s, 3H), 1.28 (t, 3H, J=7.0Hz).
B.
2.07g (3mmol) compound V-1 is dissolved in 25mL ethanol, and stirred at ambient temperature, then adds the NaOH solution of 5mL30%, then temperature rising reflux 3 hours, and now TLC display reaction completes.
Be poured in 200mL frozen water after reaction mixture cool to room temperature, stir, with 100mL × 3 dichloromethane extraction.Merge organic phase, with brine It, anhydrous sodium sulfate drying, boil off solvent on a rotary evaporator, the resistates obtained, through column chromatography purification, obtains product I-1.White foam solid, productive rate 78%,
1h NMR (DMSO-d
6, 400MHz) and δ: 7.36 (d, 1H, J=8.4Hz), 7.27 (d, 1H, J=2.0Hz), 7.21 (dd, 1H, J=2.0Hz and 8.4Hz), 7.08 (d, 2H, J=8.4Hz), 6.83 (d, 2H, J=8.4Hz), 5.73 (d, 1H, J=3.2Hz, D
2o-exchangable), 5.06 (d, 1H, J=6.4Hz, D
2o-exchangable), 4.83 (d, 1H, J=8.4Hz), 4.17-4.20 (m, 2H), 3.93-4.01 (m, 4H), 3.78-3.81 (m, 2H), (3.61 d, 1H, J=9.6Hz), (3.46 t, 1H, J=7.2Hz), 1.29 (t, 3H, J=7.0Hz).
embodiment 3
1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1-deoxidation-3,6-dehydration-β-D-Glucopyranose (I-1)
A.
Compound II per-1 uses the synthesis of method disclosed in prior art CN201310213608.8 IV-1.
5.35g (10mmol) compound IV-1 is dissolved in the methylene dichloride of 30mL drying, add 3.04g (30mmol) triethylamine, ice-water bath cooling is lower stirs, and then slowly drips the solution that methylene dichloride that 2.29g (12mmol) TsCl is dissolved in 5mL drying is made.Dropwise rear gained solution and slowly rise to room temperature, then at room temperature continue stirring 3 hours, now TLC display reaction completes.
Reaction mixture is poured in 200mL frozen water, stirs, with 100mL × 3 dichloromethane extraction.Merge organic phase, use saturated NaHCO successively
3solution and brine It, anhydrous sodium sulfate drying, boils off solvent on a rotary evaporator, and the resistates obtained, through column chromatography purification, obtains product V-1.White solid, productive rate 85%, fusing point 140-141.5 DEG C,
1h NMR (DMSO-d
6, 400MHz) δ: 7.71 (d, 2H, J=8.0Hz), 7.40 (d, 1H, J=8.0Hz), 7.36 (d, 2H, J=8.4Hz), 7.16 (s, 1H), 7.13 (dd, 1H, J=1.8Hz and8.2Hz), 7.05 (d, 2H, J=8.4Hz), 6.81 (d, 2H, J=8.8Hz), 5.29 (t, 1H, J=9.4Hz), 4.99 (t, 1H, J=9.2Hz), 4.88 (t, 1H, J=9.8Hz), 4.60 (d, 1H, J=9.6Hz), 4.07-4.10 (m, 3H), 3.93-3.98 (m, 4H), 2.36 (s, 3H), 1.93 (s, 3H), 1.90 (s, 3H), 1.66 (s, 3H), 1.28 (t, 3H, J=7.0Hz).
B.
2.07g (3mmol) compound V-1 be dissolved in by 0.83g (36mmol) sodium Metal 99.5 be dissolved in make in 20mL methyl alcohol solution, then temperature rising reflux 3 hours, now TLC show reaction complete.
Be poured in 200mL frozen water after reaction mixture cool to room temperature, stir, with 100mL × 3 dichloromethane extraction.Merge organic phase, with brine It, anhydrous sodium sulfate drying, boil off solvent on a rotary evaporator, the resistates obtained, through column chromatography purification, obtains product I-1.White foam solid, productive rate 67%,
1h NMR (DMSO-d
6, 400MHz) and δ: 7.36 (d, 1H, J=8.4Hz), 7.27 (d, 1H, J=2.0Hz), 7.21 (dd, 1H, J=2.0Hz and8.4Hz), 7.08 (d, 2H, J=8.4Hz), 6.83 (d, 2H, J=8.4Hz), 5.73 (d, 1H, J=3.2Hz, D
2o-exchangable), 5.06 (d, 1H, J=6.4Hz, D
2o-exchangable), 4.83 (d, 1H, J=8.4Hz), 4.17-4.20 (m, 2H), 3.93-4.01 (m, 4H), 3.78-3.81 (m, 2H), (3.61 d, 1H, J=9.6Hz), (3.46 t, 1H, J=7.2Hz), 1.29 (t, 3H, J=7.0Hz).
embodiment 4-10
With reference to the operation steps of embodiment 1-3, prepare the compound shown in table 1.
Compound prepared by table 1 embodiment 4-10
embodiment 11
Activeconstituents, pregelatinized Starch and Microcrystalline Cellulose are sieved, abundant mixing, add polyvinylpyrrolidonesolution solution, mixing, softwood processed, sieve, wet granular processed, in 50-60 DEG C of drying, by Sodium carboxymethyl starch, Magnesium Stearate and talcum powder sieve in advance, then join compressing tablet in above-mentioned particle.
embodiment 12
Activeconstituents, pregelatinized Starch and Microcrystalline Cellulose are sieved, abundant mixing, add polyvinylpyrrolidonesolution solution, mixing, softwood processed, sieve, wet granular processed, in 50-60 DEG C of drying, by Sodium carboxymethyl starch, Magnesium Stearate and talcum powder sieve in advance, then join compressing tablet in above-mentioned particle.
embodiment 13
Activeconstituents, pregelatinized Starch and Microcrystalline Cellulose are sieved, fully mixes, add polyvinylpyrrolidonesolution solution, mixing, softwood processed, sieves, wet granular processed, in 50-60 DEG C of drying, Magnesium Stearate and talcum powder are sieved in advance, then joins in above-mentioned particle, encapsulated, to obtain final product.
embodiment 14
Activeconstituents, pregelatinized Starch and Microcrystalline Cellulose are sieved, fully mixes, add polyvinylpyrrolidonesolution solution, mixing, softwood processed, sieves, wet granular processed, in 50-60 DEG C of drying, Magnesium Stearate and talcum powder are sieved in advance, then joins in above-mentioned particle, encapsulated, to obtain final product.
embodiment 15
In distilled water, first add distilled water and citric acid, stirring and dissolving and after, add sample again, low-grade fever makes dissolving, and adjust pH is 4.0-5.0, add 0.2 gram of activated carbon, stirred at ambient temperature 20 minutes, filters, filtrate, strength of solution is determined in middle detection, by the 5 milliliters of packing of every ampulla, high-temperature sterilization 30 minutes, obtains injection liquid.
embodiment 16
In distilled water, first add distilled water and citric acid, stirring and dissolving and after, add sample again, low-grade fever makes dissolving, and adjust pH is 4.0-5.0, add 0.2 gram of activated carbon, stirred at ambient temperature 20 minutes, filters, filtrate, strength of solution is determined in middle detection, by the 5 milliliters of packing of every ampulla, high-temperature sterilization 30 minutes, obtains injection liquid.
embodiment 17
Preparation technology: get water for injection 80ml, adds main ingredient, after N.F,USP MANNITOL, lactose, poloxamer be stirred to dissolve, the Citric Acid adding 1mol/L regulates PH to 7.0-9.0, mends and adds water to 100ml.Add 0.5g gac, stir 20 minutes at 30 DEG C, de-charcoal, adopt filtering with microporous membrane degerming, filtrate carries out packing by often propping up 1ml, and pre-freeze is after 2 hours, and freezing lower drying under reduced pressure 12 hours, after to sample temperature to room temperature, dry 5 hours again, obtained white loose block, sealed and get final product.
embodiment 18
Preparation technology: main ingredient and auxiliary material are crossed 100 mesh sieves respectively, fully mixes, then take recipe quantity auxiliary material and fully mix with main ingredient.Add tackiness agent softwood again, 14 mesh sieves are granulated, 55 DEG C of dryings, the whole grain of 12 mesh sieve, measure bag and heavily pack.
embodiment 19
The high sugar of normal SD rats height fat is fed after one month, body weight is between 200-220g/, with streptozocin low dose (8mg/kg × 3) repeatedly abdominal injection modeling (diabetes B model), measure blood-sugar content (>15mmol/L is qualified) before and after modeling.After modeling success, modeling rat is measured and body weight random packet (5/group) according to twenty-four-hour urine sugar, be respectively one group of blank group (giving equal-volume 0.5%CMC sodium solution) and some testing compound groups (15mg/kg).Fasting 16 hours before each group of rat experiment.After gavage gives experimental rat testing compound 0.5h, then gavage gives glucose (4g/kg).The urine of 0-12h time period after collection administration, with the urine sugar value of determination of glucose oxidase each time period.The results are shown in Table 2.
The different compound of table 2 affects result to rat urine sugar value
As can be seen from the above results, compound disclosed by the invention has well induction glucose in urine effect, may be used for the medicine preparing treatment diabetes B.
Claims (9)
1. there is compound and the pharmaceutically acceptable prodrug ester thereof of general formula (I) structure:
Wherein,
R
1be selected from H, F, Cl, Br, I, C
1-C
3alkyl, OR
3and SR
4;
R
2be selected from C
1-C
5alkyl and OR
5;
Wherein, R
3-R
5be selected from C
1-C
5alkyl.
2. there is compound and the pharmaceutically acceptable prodrug ester thereof of general formula (I) structure as defined in claim 1:
Wherein,
R
1be selected from F, Cl, Me, OMe and SMe;
R
2be selected from C
1-C
3alkyl and OR
5;
Wherein, R
5be selected from C
1-C
3alkyl.
3. there is compound and the pharmaceutically acceptable prodrug ester thereof of general formula (I) structure as defined in claim 2, be selected from following compounds:
4. synthesize the method with the compound of general formula (I) structure that any one of claim 1-3 defines:
Wherein, R
1and R
2definition as claimed in claim 1;
Compound II per reacts with Tosyl chloride under the existence of organic bases, optionally by 6 hydroxyl tosylations, obtains compound III; Compound III heats and obtains Compound I in the aqueous ethanolic solution or methanol aqueous solution of NaOH.
5. synthesize the method with the compound of general formula (I) structure that any one of claim 1-3 defines:
Wherein, R
1and R
2definition as claimed in claim 1;
Compound IV is reacted with Tosyl chloride under the existence of organic bases, optionally by 6 hydroxyl tosylations, obtains compound V; Compound V heats in the MeOH solution of MeONa, or heats in the aqueous ethanolic solution or methanol aqueous solution of NaOH, can obtain I.
6. as one of claim 1-3 the compound of general formula (I) structure that defines and the pharmaceutically application of acceptable prodrug ester in preparation treatment diabetes medicament thereof.
7. a pharmaceutical composition, containing, for example compound and the pharmaceutically acceptable prodrug ester thereof of general formula (I) structure of one of claim 1-3, and suitable carrier or vehicle.
8. pharmaceutical composition as claimed in claim 7, described composition is solid orally ingestible, liquid oral medicine or injection.
9. solid and liquid oral medicine comprise as claimed in claim 8: dispersible tablet, enteric coated tablet, chewable tablet, orally disintegrating tablet, capsule, granule, oral solution, and described injection preparation comprises injection liquid drugs injection, injection freeze-dried powder, infusion solutions, primary infusion.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107880006A (en) * | 2017-11-24 | 2018-04-06 | 浙江永太科技股份有限公司 | The compound as the inhibitor of SGLT 2 containing cyclohexane structure |
| CN107903231A (en) * | 2017-11-24 | 2018-04-13 | 浙江永太科技股份有限公司 | The compound as 2 inhibitor of SGLT containing adamantane structure |
| CN107903247A (en) * | 2017-11-24 | 2018-04-13 | 浙江永太科技股份有限公司 | The compound as 2 inhibitor of SGLT containing hydroxy piperidine structure |
| CN108218928A (en) * | 2016-12-13 | 2018-06-29 | 华润双鹤药业股份有限公司 | Bicyclic derivatives of glucoside and its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030617A (en) * | 2004-03-16 | 2013-04-10 | 贝林格尔.英格海姆国际有限公司 | Glucopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture |
| CN103058972A (en) * | 2013-01-17 | 2013-04-24 | 天津药物研究院 | Phenyl C-glucoside derivatives containing cyclohexane structure as well as preparation method and application thereof |
-
2014
- 2014-02-26 CN CN201410065260.7A patent/CN104861002A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030617A (en) * | 2004-03-16 | 2013-04-10 | 贝林格尔.英格海姆国际有限公司 | Glucopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture |
| CN103058972A (en) * | 2013-01-17 | 2013-04-24 | 天津药物研究院 | Phenyl C-glucoside derivatives containing cyclohexane structure as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| LAILAI WANG ET AL.: "Synthesis of New Chiral Aryl Diphosphite Ligands Derived from Pyranoside Backbone of Monosacharides and Their Application in Copper-Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Cyclic Enones", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| 万惠新等: "2型糖尿病治疗靶点钠-葡萄糖共转运蛋白2抑制剂研究进展", 《药学学报》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108218928A (en) * | 2016-12-13 | 2018-06-29 | 华润双鹤药业股份有限公司 | Bicyclic derivatives of glucoside and its preparation method and application |
| CN108218928B (en) * | 2016-12-13 | 2020-06-30 | 华润双鹤药业股份有限公司 | Bicyclic derivatives of glucoside, preparation method and application thereof |
| CN107880006A (en) * | 2017-11-24 | 2018-04-06 | 浙江永太科技股份有限公司 | The compound as the inhibitor of SGLT 2 containing cyclohexane structure |
| CN107903231A (en) * | 2017-11-24 | 2018-04-13 | 浙江永太科技股份有限公司 | The compound as 2 inhibitor of SGLT containing adamantane structure |
| CN107903247A (en) * | 2017-11-24 | 2018-04-13 | 浙江永太科技股份有限公司 | The compound as 2 inhibitor of SGLT containing hydroxy piperidine structure |
| CN107903247B (en) * | 2017-11-24 | 2019-07-02 | 浙江永太科技股份有限公司 | The compound as SGLT-2 inhibitor containing hydroxy piperidine structure |
| CN107903231B (en) * | 2017-11-24 | 2019-07-02 | 浙江永太科技股份有限公司 | The compound as SGLT-2 inhibitor containing adamantane structure |
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