CN104418847A - Process for preparing 4-(6-deoxidized-beta-D-glucopyranose)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methyl benzol - Google Patents

Process for preparing 4-(6-deoxidized-beta-D-glucopyranose)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methyl benzol Download PDF

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CN104418847A
CN104418847A CN201310409513.3A CN201310409513A CN104418847A CN 104418847 A CN104418847 A CN 104418847A CN 201310409513 A CN201310409513 A CN 201310409513A CN 104418847 A CN104418847 A CN 104418847A
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compound
acid
methyl
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赵桂龙
刘钰强
谢亚非
韩书文
魏群超
王玉丽
吴疆
徐为人
汤立达
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Tianjin Institute of Pharmaceutical Research Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings

Abstract

The invention discloses a process for preparing 4-(6-deoxidized-beta-D-glucopyranose)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methyl benzol. The invention discloses a method for preparing a deoxidation C-glucoside SGLT2 inhibitor CD-6 for preparing a medicine for treating type-II diabetes. The method has the characteristics of short step and low cost and is suitable for large-scale industrialization. The general formula of 4-(6-deoxidized-beta-D-glucopyranose)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methyl benzol is shown in the specification, wherein X is selected from Br and I.

Description

The preparation technology of 4-(6-deoxidation-β-D-glucopyranosyl)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methylbenzene
Technical field
The invention belongs to medical art, be specifically related to a kind of deoxidation C-glucosides class SGLT2 inhibitor that may be used for treating diabetes, more specifically relating to a kind of deoxidation C-glucosides class SGLT2 inhibitor can industrialized preparation method.
Background technology
The present inventor discloses compound 4-(6-deoxidation-β-D-glucopyranosyl)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methylbenzene (structural formula is as follows, and this compound label is CD-6 herein) as Na in CN201310213608.8 +-glucose cotransporter 2 (sodium-dependent glucose cotransporter2, SGLT2) inhibitor, this compound may be used for the medicine preparing treatment diabetes B.
In further studying, the present inventor finds, the method being used for preparing Compound C D-6 disclosed in CN201310213608.8 take canagliflozin as raw material (reaction scheme is as follows), because canagliflozin is expensive, and this route steps is more, therefore this route is not suitable for suitability for industrialized production.
The invention discloses the new synthetic method of a kind of Compound C D-6, have easy and simple to handle, step is short, low cost and other advantages, is applicable to large-scale industrial production.
Summary of the invention
The novel synthesis of Compound C D-6 of the present invention is as follows:
Each step reaction of the route of above-mentioned synthesis CD-6 is as follows:
(1) the first step.
Compound I alkyl lithium reagents (as n-BuLi, t-BuLi or sec-BuLi) or MAGNESIUM METAL process, be converted into corresponding lithium aryl or aryl azoviolet, then reacts with Compound II per again, the adduct III-M obtained.
(2) second step.
III-M can obtain III with acid treatment in presence of methyl alcohol.Wherein X=I or Br, described acid is selected from various mineral acid, and some organic acid, as methylsulfonic acid, tosic acid, trifluoromethanesulfonic acid, trifluoroacetic acid etc.
(3) the 3rd steps.
Compound III-M or III all with reductive agent reduction under Lewis acid exists, can obtain product IV.Reductive agent is selected from Et 3siH, Lewis acid is selected from BF 3et 2o, AlCl 3, SnCl 2, SnCl 4, ZnCl 2, TMSOTf, preferred BF 3et 2o.
(4) the 4th steps.
Compound IV removes benzyl and obtains product C D-6.The condition of debenzylation is selected from: 1) AlCl 3/ methyl-phenoxide; 2) trifluoromethanesulfonic acid/trifluoroacetic acid/dimethyl sulphide/meta-cresol/1，2-ethandithiol; 3) Iodotrimethylsilane; 4) BCl 3; 5) catalytic hydrogenation, catalyzer is selected from Pd/C and Pd (OH) 2, hydrogen source is selected from H 2, ammonium formiate, formic acid or tetrahydrobenzene.
Invention also provides the technique that a kind of crude product CD-6 purifies.Be converted into compound V by crude product CD-6 acylations, slough acyl group again after being purified by column chromatography and/recrystallization by compound V and obtain highly purified Compound C D-6.Wherein R is selected from Me, Et, Ph, p-methylphenyl, p-nitrophenyl etc.The condition of sloughing the acyl group in compound V comprises: 1) MOH/ protonic solvent/H 2o, MOH is wherein selected from NaOH, KOH, LiOH, and protonic solvent is selected from MeOH, EtOH, Virahol, propyl alcohol; 2) NaOR 1/ R 1oH, R 1be selected from Me, EtOH, n-Pr and i-Pr; 3) R 2nH 2/ protonic solvent, wherein R 2be selected from H, Me and Et, protonic solvent is selected from MeOH, EtOH, Virahol, n-propyl alcohol, the trimethyl carbinol.
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.
The synthesis of embodiment 1 compound III-M
Add the THF of 3.61g (10mmol) Compound I-1 and 60mL drying in the dry round-bottomed flask of a 250mL, add magneton, with the sealing of rubber cork after nitrogen purging.Flask is placed in liquid nitrogen-ethanol system and is cooled to-78 DEG C, starts induction stirring.The n-Butyl Lithium of 6.25mL (10mmol) 1.6M is slowly dripped with syringe, continue at such a temperature after dropwising to stir half an hour, then slowly drip by syringe the solution that THF that 4.33g (10mmol) II is dissolved in 20mL drying makes.After dropwising, reaction mixture continues stirring 1 hour at such a temperature, is then slowly warming up to room temperature, continues reaction 1 hour.Reaction mixture is poured in 400mL frozen water, stirs, uses saturated NaHCO 3solution regulates the dichloromethane extraction of pH=4-6,100mL × 3.Merge organic phase, weak brine washs, and anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, resistates is the crude product of III-M, ESI-MS, m/z=715 ([M+H] +).This crude product, without purifying, is directly used in next step reaction.
The synthesis of embodiment 2 compound III
Add the THF of 4.08g (10mmol) Compound I-2,0.29g (12 mmol) MAGNESIUM METAL and 20mL drying in the dry round-bottomed flask of a 100mL, add magneton, stirred at ambient temperature.Add a granule iodine, then the whole flask hot water heating of 65 DEG C, causes until react and is exhausted by much part metals magnesium.Flask ice-water bath is cooled, slowly drips by dropping funnel the solution that THF that 4.33g (10mmol) II is dissolved in 20mL drying makes.After dropwising, reaction mixture continues stirring 1 hour at such a temperature.Under ice-water bath cooling, slowly drip 2.88g (30mmol) methylsulfonic acid by dropping funnel and be dissolved in the solution that 20mL methyl alcohol makes, dropwise rear room temperature for overnight.Reaction mixture is poured in 200mL frozen water, stirs half an hour, uses saturated NaHCO 3solution regulates the dichloromethane extraction of pH=4-6,50mL × 3.Merge organic phase, weak brine washs, and anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, resistates is the crude product of III, ESI-MS, m/z=729 ([M+H] +).This crude product, without purifying, is directly used in next step reaction.
The synthesis of embodiment 3 compound IV
The crude product of compound III prepared by embodiment 1 is dissolved in the methylene dichloride of 50mL drying in the round-bottomed flask of 250mL, adds 2.33g (20mmol) Et 3siH, stirs under-30 DEG C of coolings.The solution that methylene dichloride that 1.42g (10mmol) boron trifluoride diethyl etherate is dissolved in 5mL drying makes slowly is dripped by dropping funnel.After dropwising, reaction mixture continues stirring and is then warming up to room temperature gradually in 1 hour at-30 DEG C, and at room temperature continues stirring 5 hours, and TLC shows reaction to be completed.In compound of reaction, carefully add 20mL saturated sodium bicarbonate solution, be poured in 200mL frozen water after continuing to stir half an hour, stir, the dichloromethane extraction of 100mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, and resistates column chromatography purification, obtains the sterling of IV, white foam solid, 1h NMR (DMSO-d 6, 400MHz), δ 7.26-7.37 (m, 14H), 7.13-7.20 (m, 4H), 6.93-6.98 (m, 5H), 6.63 (d, 1H, J=3.6Hz), 4.88-4.94 (m, 2H), 4.70 (d, 1H, J=10.8Hz), 4.37 (d, 1H, J=10.4Hz), 4.21 (d, 1H, J=9.6Hz), 4.16 (d, 1H, J=12.0Hz), 4.09 (d, 1H, J=12.0Hz), 3.90 (d, 1H, J=10.4Hz), 3.76 (t, 1H, J=9.0Hz), 3.53-3.60 (m, 2H), 3.32 (t, 1H, J=9.0Hz), 2.33 (s, 3H), 1.34 (d, 3H, J=6.0Hz).
The synthesis of embodiment 4 compound IV
The crude product of compound III prepared by embodiment 2 is dissolved in the methylene dichloride of 50mL drying in the round-bottomed flask of 250mL, adds 2.33g (20mmol) Et 3siH, stirs under-30 DEG C of coolings.The solution that methylene dichloride that 1.42g (10mmol) boron trifluoride diethyl etherate is dissolved in 5mL drying makes slowly is dripped by dropping funnel.After dropwising, reaction mixture continues stirring and is then warming up to room temperature gradually in 1 hour at-30 DEG C, and at room temperature continues stirring 5 hours, and TLC shows reaction to be completed.In compound of reaction, carefully add 20mL saturated sodium bicarbonate solution, be poured in 200mL frozen water after continuing to stir half an hour, stir, the dichloromethane extraction of 100mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, and resistates column chromatography purification, obtains the sterling of IV, white foam solid, 1h NMR (DMSO-d 6, 400MHz), δ 7.26-7.37 (m, 14H), 7.13-7.20 (m, 4H), 6.93-6.98 (m, 5H), 6.63 (d, 1H, J=3.6Hz), 4.88-4.94 (m, 2H), 4.70 (d, 1H, J=10.8Hz), 4.37 (d, 1H, J=10.4Hz), 4.21 (d, 1H, J=9.6Hz), 4.16 (d, 1H, J=12.0Hz), 4.09 (d, 1H, J=12.0Hz), 3.90 (d, 1H, J=10.4Hz), 3.76 (t, 1H, J=9.0Hz), 3.53-3.60 (m, 2H), 3.32 (t, 1H, J=9.0Hz), 2.33 (s, 3H), 1.34 (d, 3H, J=6.0Hz).
The synthesis of embodiment 5 Compound C D-6
3.49g (5mmol) compound IV is dissolved in the methyl-phenoxide of 20mL drying, and-10 DEG C of lower stirrings of cooling, slowly add 3.33g (25mmol) anhydrous AlCl 3, be slowly raised to room temperature after adding, then stir 1 hour, TLC shows reaction to be completed.Be poured into after reaction mixture is slightly cold in 200mL frozen water, stir, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, evaporate to dryness on a rotary evaporator, ethyl acetate/petroleum ether (1/10by v/v) 4mL is added in the white solid of resistates gained after short column chromatography purifying, room temperature for overnight, collected by suction solid, drying is CD-6.White solid, fusing point 139-141 DEG C. 1H NMR(DMSO-d 6,400MHz),δ7.56-7.60(m,2H),7.26(d,1H,J=3.6Hz),7.17-7.21(m,3H),7.10-7.12(m,2H),6.78(d,1H,J=3.6Hz),4.92(d,1H,J=5.2Hz),4.86(d,1H,J=4.0Hz),4.68(d,1H,J=5.2Hz),4.14(d,1H,J=16.0Hz),4.09(d,1H,J=16.0Hz),3.96(d,1H,J=9.2Hz),3.14-3.31(m,3H),2.90-2.95(m,1H),2.25(s,3H),1.15(d,3H,J=6.0Hz); 13C NMR(DMSO-d 6,100MHz),δ162.54,160.12,143.57,140.19,138.23,137.37,134.85,130.47,129.64,128.85,126.94,126.86,126.31,126.05,123.34,115.93,115.72,81.32,78.16,75.71,75.59,74.81,33.35,18.75,18.23.
The synthesis of embodiment 6 Compound C D-6
3.49g (5mmol) compound IV is dissolved in the acetonitrile of 10mL drying, and ice-water bath cooling is lower stirs, and slowly adds 10.00g (50mmol) TMSI, slowly room temperature is raised to after adding, room temperature for overnight, then temperature rising reflux 1 hour, TLC display reaction completes substantially.Be poured into after reaction mixture is slightly cold in 300mL frozen water, stir, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, evaporate to dryness on a rotary evaporator, resistates obtains a white solid after short column chromatography purifying, adds ethyl acetate/petroleum ether (1/10by v/v) 4mL, room temperature for overnight, collected by suction solid, drying is CD-6.Structural characterization data are consistent with embodiment 5.
The synthesis of embodiment 7 Compound C D-6
3.49g (5mmol) compound IV is dissolved in the methylene dichloride of 20mL drying, is cooled to-50 DEG C, stirs, slowly drips the BCl of 25mL (25mmol) 1M 3methylene dichloride, be slowly raised to room temperature after adding, then continue stirring 1 hour, TLC show reaction completes.Be poured into after reaction mixture is slightly cold in 200mL frozen water, stir, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, successively use saturated NaHCO 3solution and weak brine washing, anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, add ethyl acetate/petroleum ether (1/10by v/v) 4mL in resistates, room temperature for overnight, collected by suction solid, drying is CD-6.Structural characterization data are consistent with embodiment 5.
The synthesis of embodiment 8 Compound C D-6 crude product
3.49g (5mmol) compound IV is dissolved in 20mL THF, and add 0.5g 10%Pd/C, under room temperature, catalytic hydrogenation is spent the night.Reaction mixture suction filtration, filtrate is evaporate to dryness on a rotary evaporator, and add ethyl acetate/petroleum ether (1/10by v/v) 4mL in resistates, room temperature for overnight, collected by suction solid, drying is CD-6.Structural characterization data are consistent with embodiment 5.
The synthesis of embodiment 9 Compound C D-6
3.49g (5mmol) compound IV is dissolved in the mixed solvent be made up of 1.5mL trifluoroacetic acid, 9mL dimethyl thioether, 2.4mL m-methyl phenol and 0.6mL dithioglycol, is cooled to-15 DEG C.Slowly drip 3mL trifluoromethanesulfonic acid.Slowly be raised to room temperature after adding, then continue stirring 1 hour, TLC shows reaction to be completed.Be poured into after reaction mixture is slightly cold in 200mL frozen water, stir, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, evaporate to dryness on a rotary evaporator, resistates obtains a white solid after short column chromatography purifying, adds ethyl acetate/petroleum ether (1/10by v/v) 4mL, room temperature for overnight, collected by suction solid, drying is CD-6.Structural characterization data are consistent with embodiment 5.
Embodiment 10 is by CD-6 synthetic compound V-1
1.29g (3mmol) Compound C D-6 crude product is dissolved in 10mL pyridine, adds 0.2g DMAP, stirs under ice-water bath cooling, 7mL acetic anhydride is slowly dripped by dropping funnel, after dropwising, reaction mixture at room temperature stirs and spends the night, and TLC shows reaction to be completed.Reaction mixture is poured in 100mL frozen water, stirs, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, respectively with the hydrochloric acid of 100mL 2% and weak brine washing, anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, resistates obtains the sterling of V-1 through short column chromatography purifying.White solid, fusing point 149-151 DEG C. 1H NMR(DMSO-d 6,400MHz),δ7.55-7.59(m,2H),7.27(d,1H,J=3.6Hz),7.15-7.21(m,5H),6.74(d,1H,J=3.6Hz),5.26(t,1H,J=9.6Hz),4.97(t,1H,J=9.6Hz),4.81(t,1H,J=9.6Hz),4.55(d,1H,J=9.6Hz),4.12(s,2H),3.82-3.86(m,1H),2.24(s,3H),2.02(s,3H),1.91(s,3H),1.70(s,3H),1.12(d,3H,J=6.4Hz).
Embodiment 11 is by CD-6 synthetic compound V-2
1.29g (3mmol) Compound C D-6 crude product is dissolved in 10mL pyridine, add 0.2g DMAP, stir under ice-water bath cooling, 2.11g (15mmol) Benzoyl chloride is slowly dripped by dropping funnel, after dropwising, reaction mixture at room temperature stirs and spends the night, and TLC shows reaction to be completed.Reaction mixture is poured in 100mL frozen water, stirs, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, respectively with the hydrochloric acid of 100mL2% and weak brine washing, anhydrous sodium sulfate drying, on a rotary evaporator evaporate to dryness, resistates obtains the sterling of V-2 through short column chromatography purifying, white solid, MS, m/z=741 ([M+H] +).
Embodiment 12 is by V-1 synthetic compound CD-6
1.11g (2mmol) compound V-1 is dissolved in 10mL methyl alcohol, stirred at ambient temperature, then the NaOH solution adding 1mL 30%, then temperature rising reflux half an hour, and TLC shows reaction to be completed.Be poured into after reaction mixture is slightly cold in 50mL frozen water, stir, regulate pH=7 with hydrochloric acid, with the extraction into ethyl acetate of 50mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, evaporate to dryness on a rotary evaporator, resistates is through too short purification by silica gel column chromatography, residue with ethyl acetate/sherwood oil (1/10by v/v) recrystallization obtained, obtain the sterling of CD-6, structural characterization data are consistent with embodiment 4.
Embodiment 13 is by V-1 synthetic compound CD-6
0.2g sodium Metal 99.5 joins in 20mL anhydrous methanol, stirred at ambient temperature, until sodium Metal 99.5 disappears, then adds 1.11g (2mmol) compound V-1, continues stirring 5 hours, and now TLC display reaction completes.Add dry storng-acid cation exchange resin 2g, room temperature for overnight, until pH=7.Suction filtration removing resin, filtrate is evaporate to dryness on a rotary evaporator, the resistates obtained through too short purification by silica gel column chromatography, residue with ethyl acetate/sherwood oil (1/10by v/v) recrystallization obtained, obtain the sterling of CD-6, structural characterization data are consistent with embodiment 4.
Embodiment 14 is by V-2 synthetic compound CD-6
1.48g (2mmol) compound V-2 is dissolved in the saturated NH3/ methyl alcohol of 20mL, stirs and spend the night at 50 DEG C, and TLC shows reaction to be completed.Be poured into after compound of reaction is slightly cold in 300mL frozen water, stir, the extraction into ethyl acetate of 50mL × 3.Merge organic phase, weak brine washs, anhydrous sodium sulfate drying, evaporate to dryness on a rotary evaporator, resistates through too short purification by silica gel column chromatography, the residue with ethyl acetate obtained/sherwood oil recrystallization, obtain the sterling of CD-6, structural characterization data are consistent with embodiment 4.

Claims (12)

1. a preparation method for CD-6 compound, is characterized in that, comprises the steps:
(1) Compound I alkyl lithium reagents or MAGNESIUM METAL process, is converted into corresponding lithium aryl or aryl azoviolet; Then react with Compound II per again, obtain adduct III-M; Wherein X is selected from I or Br;
(2) compound III-M obtains compound III under methyl alcohol and acid treatment;
(3) compound III reduction under Lewis acid exists obtains compound IV;
(4) compound IV is sloughed benzyl and is converted into Compound C D-6.
2. preparation method as claimed in claim 1, the alkyl lithium reagents described in step (1) is selected from n-BuLi, t-BuLi or sec-BuLi.
3. preparation method as claimed in claim 1, the acid described in step (2) is selected from mineral acid, methylsulfonic acid, tosic acid, trifluoromethanesulfonic acid or trifluoroacetic acid.
4. preparation method as claimed in claim 1, the reductive condition described in step (3) is for selecting reductive agent Et 3siH; Described Lewis acid is selected from BF 3et 2o, AlCl 3, SnCl 2, SnCl 4, ZnCl 2, TMSOTf.
5. preparation method as claimed in claim 1, described in step (4), the condition of debenzylation is selected from: 1) AlCl 3/ methyl-phenoxide; 2) trifluoromethanesulfonic acid/trifluoroacetic acid/dimethyl sulphide/meta-cresol/1，2-ethandithiol; 3) Iodotrimethylsilane; 4) BCl 3; 5) catalytic hydrogenation; Catalyzer is selected from Pd/C and Pd (OH) 2, hydrogen source is selected from H 2, ammonium formiate, formic acid or tetrahydrobenzene.
6. the compound of formula IV,
7. the compound of formula III,
8. the compound of formula III-M,
9. preparation method as claimed in claim 1, also comprises the purification step of Compound C D-6,
It is characterized in that,
(1) Compound C D-6 acylations is converted into compound V;
(2) compound V sloughs acyl group in the basic conditions and is converted into CD-6;
Wherein, R is methyl, ethyl, propyl group, phenyl, p-methylphenyl, p-nitrophenyl.
10. preparation method as claimed in claim 9, the acylting agent in described purification step (1) be selected from diacetyl oxide, Acetyl Chloride 98Min., propionyl chloride, Benzoyl chloride, to methyl benzoyl chloride, paranitrobenzoyl chloride.
11. preparation methods as claimed in claim 9, the basic reaction conditions in described purification step (2) is selected from:
1) MOH/ protonic solvent/H 2o, MOH is wherein selected from NaOH, KOH, LiOH, and described protonic solvent is selected from MeOH, EtOH, Virahol, propyl alcohol; 2) NaOR 1/ R 1oH, R 1be selected from Me, EtOH, n-Pr and i-Pr; 3) R 2nH 2/ protonic solvent, wherein R 2be selected from H, Me and Et, described protonic solvent is selected from MeOH, EtOH, Virahol, n-propyl alcohol, the trimethyl carbinol.
12. compound V,
Wherein, R is selected from Me, Et, Ph, p-methylphenyl and p-nitrophenyl.
CN201310409513.3A 2013-09-10 2013-09-10 Process for preparing 4-(6-deoxidized-beta-D-glucopyranose)-2-[5-(4-fluorophenyl) thiophene-2-methyl]-1-methyl benzol Pending CN104418847A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060009400A1 (en) * 2004-07-06 2006-01-12 Boehringer Ingelheim International Gmbh D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture
CN102264714A (en) * 2008-10-17 2011-11-30 詹森药业有限公司 Process for the preparation of compounds useful as inhibitors of sglt
CN102307577A (en) * 2009-02-13 2012-01-04 贝林格尔.英格海姆国际有限公司 Pharmaceutical composition comprising an SGLT2 inhibitor, a DPP-IV inhibitor and a third antidiabetic agent, and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060009400A1 (en) * 2004-07-06 2006-01-12 Boehringer Ingelheim International Gmbh D-xylopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture
CN102264714A (en) * 2008-10-17 2011-11-30 詹森药业有限公司 Process for the preparation of compounds useful as inhibitors of sglt
CN102307577A (en) * 2009-02-13 2012-01-04 贝林格尔.英格海姆国际有限公司 Pharmaceutical composition comprising an SGLT2 inhibitor, a DPP-IV inhibitor and a third antidiabetic agent, and uses thereof

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Application publication date: 20150318