CN104610208B - Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application - Google Patents
Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application Download PDFInfo
- Publication number
- CN104610208B CN104610208B CN201310541681.8A CN201310541681A CN104610208B CN 104610208 B CN104610208 B CN 104610208B CN 201310541681 A CN201310541681 A CN 201310541681A CN 104610208 B CN104610208 B CN 104610208B
- Authority
- CN
- China
- Prior art keywords
- crystal formation
- trans
- glucopyranoses
- aminomethyl phenyl
- dideoxies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
Abstract
The invention belongs to pharmaceutical technology field, specifically disclose a kind of crystal formation A of dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] the D glucopyranoses (DO) of deoxidation C glucose glycosides SGLT2 inhibitor (1S) 1,6 and its production and use.Crystal formation X ray powder diffraction characteristic absorption peaks（2θ）It is worth and is：3.80、6.54、8.34、9.88、11.34、14.52、15.08、18.06、18.96、19.38、19.94、20.92、21.72、22.28；2 θ measurement errors are ± 0.2.The features such as crystal formation has the purity that apparent condition is stable, can further improve the compound, preserves stable, possesses the characteristics of directly supplying raw material medicine.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of phenyl C- glucosides containing deoxyglucose structure and derives
A kind of crystal formation of thing, and in particular to (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) methyl
Phenyl]-D- glucopyranoses crystal formation A, and the crystal formation preparation method and application.
Background technology
The present inventor is with regard to (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) methylbenzenes
Base]-D- glucopyranoses (for convenience of description, hereinafter referred to as DO) are used as Na+- glucose cotransporter 2（Or be 2 type sodium
Glucose cotransporter, sodium-dependent glucose cotransporter2, is abbreviated as SGLT2）Inhibitor is submitted
Application for a patent for invention (CN201310016846.X).The compound can be used for the pharmaceutical composition for preparing treatment diabetes, its
Chemical structural formula is as follows：
In research process, the inventors discovered that, the later stage for preparing above-claimed cpd DO final step is from solution
The isolated product by solvent evaporated, its form is a kind of solid matter between white foam and white solid,
And the state fluctuated between each batch it is indefinite, it is difficult to keep constant apparent condition, be not suitable for used directly as bulk drug.
Simultaneously as the compound often shows certain foam characteristic, so that the difficulty further purified is increased, it is high to preparing
The bulk drug of purity brings certain difficulty.
The content of the invention
Therefore, it is an object of the invention to overcome drawbacks described above there is provided a kind of DO crystal formation A, the crystal formation has stable
Apparent condition, help further to improve DO purity, and improve storage stability, preparation can be stably supplied former
Expect medicine, and additionally provide the preparation method and application of the crystal formation.
The invention provides a kind of (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) first
Base phenyl]-D- glucopyranoses (DO) crystal formation A, X-ray powder diffraction (PXRD, the Powder X- represented with 2 θ angles
Ray Diffraction) 3.80,6.54,8.34,9.88,11.34,14.52,15.08,18.06,18.96,19.38,
19.94th, 20.92,21.72,22.28 ° of vicinity have diffraction maximum.
According to the present invention crystal formation A, wherein, its X-ray powder diffraction interplanar distance d values be 23.23,13.50,
10.59、8.95、7.80、6.10、5.87、4.91、4.68、4.58、4.45、4.24、4.09、3.99 Position vicinity tool
There is diffraction maximum.Preferably, corresponding relation is as shown in table 1 between the interplanar distance d values and 2 θ angles.
Corresponding relation between the interplanar distance d values of table 1 and 2 θ
According to the crystal formation A of the present invention, wherein, its differential thermal analysis (DTA, Differential Thermal Analysis)
Collection of illustrative plates can have endothermic peak at 146 DEG C.
According to the crystal formation A of the present invention, wherein, its X-ray powder diffraction collection is as shown in Figure 2.
Present invention also offers the method for preparing above-mentioned crystal formation A, this method includes：By (1S) -1,6- dideoxy -1- [4-
Methoxyl group -3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl]-D- glucopyranoses are dissolved in a kind of good solvent, then may be used
The solution is heated, a kind of poor solvent is slowly added to, then slowly cooling crystallization, collected by suction crystallization, Ran Hougan under agitation
It is dry, obtain crystal formation A.
The method according to the invention, wherein, good solvent is selected from acetic acid, acetone, methanol, ethanol, isopropanol, poor solvent
For water；Or, good solvent is selected from ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isopropyl acetate, no
Good solvent is selected from n-hexane, hexamethylene, isopropyl ether, ether, petroleum ether.
The method according to the invention, wherein, (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- positive third
Butylcyclohexyl) aminomethyl phenyl]-D- glucopyranoses/good solvent/poor solvent mass/volume/volume ratio (g/mL/mL)
For 1：5~10：3~30, preferably 1：7：7.
Preferably, operation is dried using vacuum oil pump, drying time is 4~8 hours, preferably 5 hours.
Present invention also offers a kind of pharmaceutical composition, described pharmaceutical composition includes the crystal formation A of the invention of effective dose
With one or more pharmaceutically acceptable auxiliary materials.The pharmaceutically acceptable auxiliary material can be to maintain the matrix of pharmaceutical dosage form
Or auxiliary material, by being selected according to different medicaments or composition is used, be optionally included with carrier, excipient, diluent,
Filler, adhesive, disintegrant, lubricant, glidant, effervescent agent, flavouring, preservative, coating material etc..Excipient includes
For example microcrystalline cellulose, lactose, pregelatinized starch, starch, dextrin, calcium phosphate, sucrose, dextran, mannitol, sorbierite,
One or more of combinations in glucose, fructose, water, polyethylene glycol, propane diols, glycerine, cyclodextrin, cyclodextrine derivatives
Thing.Filler includes such as lactose, sucrose, dextrin, starch, pregelatinized starch, mannitol, sorbierite, calcium monohydrogen phosphate, sulfuric acid
Calcium, calcium carbonate, one or more of compositions of microcrystalline cellulose.Adhesive includes such as sucrose, starch, PVP, carboxylic first
Base sodium cellulosate, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, polyethylene glycol, medicinal alcohol, one kind of water or several
The composition planted.Disintegrant includes such as starch, crosslinking polyvidone, Ac-Di-Sol, low substituted hydroxy-propyl fiber
Element, carmethose, one or more of compositions of gas-producing disintegrant.
According to the pharmaceutical composition of the present invention, wherein, described pharmaceutical composition can be solid orally ingestible, liquid oral
Preparation or injection.Preferably, the solid orally ingestible include dispersible tablet, enteric coatel tablets, chewable tablets, oral disintegrating tablet, capsule or
Granula；The liquid oral medicine includes oral solution；The injection include injection liquid drugs injection, injection freeze-dried powder,
Big transfusion or primary infusion.
Prepared present invention also offers crystal formation A or according to the crystal formation A of the method preparation of the present invention for treating diabetes
Pharmaceutical composition in purposes.The inventor has discovered that DO has SGLT2 inhibitory action, it can be used to make as active ingredient
Medicine in terms of standby diabetes.And model validation is drained by suppression in vitro to humanization SGLT2 and rat glucose in urine,
The crystal formation A of the present invention has higher SGLT2 inhibitory activity.
DO of the present invention crystal formation A is effective in comparatively wide dosage range.The dosage for example taken daily
About in the range of 1mg~500mg/ people, it is divided into and once or is for several times administered.Actually take DO of the present invention crystal formation A agent
Amount can be determined by doctor according to relevant situation.These situations include：The condition of patient, method of administration, the age,
Body weight, the individual reaction to medicine, order of severity of symptom etc..
Compared with the DO samples by being directly evaporated made from the modes such as solution between foam-like and normal solid, this
There is the prepared DO crystal formations A of invention good appearance stability (to be white solid, rather than with a certain degree of between batch
Foam-like feature) and reappearance, and purity further improves.For example, the present inventor is found by experiment that, crystal formation A is even
In the range of the continuous batch for preparing 10 batches, its outward appearance is stable, is normally white solid, and is analyzed by PXRD and DTA
Every batch is stable crystal formation A.In addition, each batch by HPLC analyses, crystal formation A purity is 99.40%~99.60%, significantly
Higher than the purity 98.04% of DO raw materials.
In addition, the crystal formation A of the present invention also has good storage stability.For example, the present inventor is by experimental verification, should
Crystal formation A at two weeks by a definite date in light, heat, the stability experiment of vapor, its impurity is not significantly increased, thus with good
Bin stability.
Based on above-mentioned characteristic, crystal formation A of the invention can as DO bulk drugs stable supplying source, be more suitable for industrial metaplasia
Production.
Brief description of the drawings
Hereinafter, embodiment of the present invention is described in detail with reference to accompanying drawing, wherein：
Fig. 1 shows differential thermal analysis (DTA) collection of illustrative plates of obtained crystal formation A in embodiment 1；
Fig. 2 shows the PXRD collection of illustrative plates of obtained crystal formation A in embodiment 1.
Embodiment
The present invention is further illustrated below by specific embodiment, it should be understood, however, that, these embodiments are only
It is used for specifically describing in more detail, and is not to be construed as limiting the present invention in any form.
This part carries out general description to the material and test method that are arrived used in present invention experiment.Although being
It is it is known in the art that still the present invention still uses up herein to realize many materials used in the object of the invention and operating method
It may be described in detail.It will be apparent to those skilled in the art that within a context, if not specified, material therefor of the present invention and behaviour
It is well known in the art as method.
With the following Examples, the present invention is as follows to crystal formation A condition determination：
X-ray powder diffraction（PXRD）Condition：
Instrument：Rigaku D/Max-2500 types 18kW
Diffractometer：Polycrystal powder diffractometer
Target：Cu-K α are radiated,2 θ=3~50 °
Pipe pressure：40KV
Guan Liu：100mA
Sweep speed：8℃/min
Crystalline graphite monochromator
DS/SS=1°
RS：0.3mm
Differential thermal analysis (DTA) condition：
Instrument：Rigaku PTC-10A TG-DTA analyzers
Heating rate：10℃/min
Scan temperature range：0~300 DEG C
Reference substance：Al2O3
Sample size：5.8mg crystal formation A to be measured
High performance liquid chromatography (HPLC) condition：
Chromatographic column：C18, 150mm × 4.6mm, 5 μm
Mobile phase：Methanol/water/acetic acid=70/30/0.25
Wavelength：230nm
Flow velocity：0.8ml/min
Sample size：10μL
Column temperature：35℃
Instrument：The general general L6 liquid chromatographs of analysis
Hitachi's L-7250 automatic samplers
The general general LC Win chromatographic work stations of analysis
Embodiment 1
The present embodiment is used for the crystal formation A and its preparation process for illustrating DO of the present invention.
Prepare DO and be used as raw material.It is referred to following reaction process：
Specifically preparation process can be：
The THF that 32.5g (0.1mol) compound I and 300mL are dried is added in one 1L drying round-bottomed flask, magnetic is added
Sealed after son, nitrogen purging with rubber cork.Flask, which is placed in liquid nitrogen-ethanol system, is cooled to -78 DEG C, starts electromagnetic agitation.
Continue stirring half at such a temperature slowly with syringe dropwise addition 62.5mL (0.1mol) 1.6M n-BuLi, after completion of dropping small
When, 43.3g (0.1mol) II is then slowly added dropwise by syringe and is dissolved in the solution that the THF of 200mL dryings is made.Reaction mixing
Thing continues stirring 1 hour at such a temperature, is then slowly ramped to room temperature reaction 1 hour.Reactant mixture is poured into 400mL ice
In water, saturation NaHCO is used in stirring3Solution adjusts pH=4-6, the dichloromethane extraction of 100mL × 3.Merge organic phase, weak brine
Washing, anhydrous sodium sulfate drying is evaporated on a rotary evaporator, and residue is III-M crude product.The crude product without purifying,
It is directly used in next step reaction.
The compound III-M of above-mentioned preparation crude product is dissolved in 1L round-bottomed flask in the dichloromethane of 500mL dryings,
Add 23.3g (0.2mol) Et3SiH, is stirred under being cooled down at -30 DEG C.14.2g (0.1mmol) is slowly added dropwise by dropping funel
BFEE is dissolved in the solution that the dichloromethane of 50mL dryings is made.After completion of dropping, reactant mixture at -30 DEG C after
Continuous stirring is then gradually heating to room temperature for 1 hour, and continues to stir 5 hours at room temperature, and TLC display reactions are completed.Toward reaction
200mL saturated sodium bicarbonate solutions are carefully added into compound, continues to be poured into 2000mL frozen water after stirring half an hour, stirs
Mix, the dichloromethane extraction of 500mL × 3.Merge organic phase, weak brine is washed, anhydrous sodium sulfate drying, on a rotary evaporator
It is evaporated, the purifying of residue column chromatography obtains IV sterling, white solid, 105-106.5 DEG C of fusing point.
33.1g (50mmol) compounds IV is dissolved in 200mL THF, adds 5.0g10%Pd/C, at room temperature catalytic hydrogenation mistake
Night.Reactant mixture suction filtration, filtrate is evaporated on a rotary evaporator, and residue obtains one in vain after purification by short column column chromatography
Color foaming solid, as DO.White has the solid of foam property.
Take product DO made from the 1.00g above methods to be placed in 100mL round-bottomed flask, add ethyl acetate 7mL, stir
Mix, with 50 DEG C of hot water heating, obtain the solution of a clarification.Then 7mL n-hexanes are slowly added dropwise into round-bottomed flask, are added dropwise
After finishing, remove and be stirred overnight under heating source (hot water), Temperature fall, obtain a white magma shape system.Collected by suction knot
Crystalline substance, and dried 5 hours at 30 DEG C in vacuum oil pump, DO of the present invention white solid 0.71g is obtained, the rate of recovery is 71%.
DO crystal formations A differential thermal analysis (DTA) collection of illustrative plates and X-ray diffraction (PXRD) collection of illustrative plates is distinguished as depicted in figs. 1 and 2,
Can determine that DO crystal formations made from the present embodiment is crystal formation A.
Embodiment 2-10
With reference to the operating method of embodiment 1, using 1.00g DO as raw material, related experiment parameter is converted, still can be with
Prepare DO crystal formation A (table 2).
DO crystal formation A is prepared under the different experiments parameter of table 2.
| Embodiment | Good solvent and its volume | Poor solvent and its volume | Temperature (DEG C) when solvent is mixed | Yield (%) |
| 2 | Ethyl acetate 5mL | Hexamethylene 20mL | 45 | 71 |
| 3 | N-propyl acetate 10mL | Ether 10mL | 35 | 68 |
| 4 | Isopropyl acetate 7mL | Isopropyl ether 10mL | 50 | 66 |
| 5 | N-butyl acetate 8mL | Petroleum ether 10mL | 50 | 64 |
| 6 | Isobutyl acetate 10mL | N-hexane 6mL | 50 | 76 |
| 7 | Ethanol 7mL | Water 10mL | 50 | 78 |
| 8 | Acetone 7mL | Water 10mL | 50 | 74 |
| 9 | Acetic acid 7mL | Water 10mL | 50 | 74 |
| 10 | Methanol 10mL | Water 15mL | 50 | 63 |
It is DO crystal formation A that the white solid in above-described embodiment is determined by DTA and PXRD.
Embodiment 11
The present embodiment is used for the preparation for illustrating the tablet of the DO crystal formations A containing the present invention.
By sample crystal formation A, pregelatinized starch and microcrystalline cellulose sieving made from embodiment 1, it is sufficiently mixed with recipe quantity,
Add the solution containing recipe quantity polyvinylpyrrolidone, mixing, softwood processed, sieving, wet granular processed, in 50~60 DEG C of dryings；
Then Sodium carboxymethyl starch, magnesium stearate and talcum powder are sieved in advance, above-mentioned dried particle is added to recipe quantity
In, tabletting produces the tablet containing DO crystal formations A.
Embodiment 12
The method recorded according to document (Meng, W.et al, J.Med.Chem., 2008,51,1145-1149) determines real
Apply the IC that the crystal formation A of DO made from example 1 suppresses to SGLT2 and SGLT150Value.Measurement result is as shown in table 3 below：
The IC that table 3.DO crystal formation A suppresses to SGLT2 and SGLT150Value
According to IC in upper table50The measurement result of value understands that DO crystal formation A is the SGLT2 inhibitor of strong selectivity.
Embodiment 13
The purity of crystal formation A made from embodiment 1 is determined using HPLC, its purity is 99.54%.And be used to prepare crystal formation A's
It is 98.04% that DO raw materials, which measure purity,.It can thus be appreciated that crystal formation A purity is significantly improved, the batch production of medicine is particularly suited for.
Embodiment 14
DO crystal formations A made from embodiment 1 is subjected to influence factor experiment with DO raw materials as a comparison, respectively in illumination
Put under conditions of (natural sunshine, about averagely 80000Lx), high temperature (60 DEG C) and high humidity (80% relative humidity at 40 DEG C)
Two weeks (14 days) are put, outward appearance, impurity number and impurity level (being determined with HPLC) were compared with the 0th day.Result of the test is shown in Table 4 respectively~
6。
The light durability test data of table 4.
The thimble test data of table 5.
The high humidity stability test data of table 6.
In table 3~5, the stability test under the illumination of two weeks, high temperature, super-humid conditions by a definite date, the present invention is brilliant
Visible change does not occur for type A outward appearance, and crystal formation keeps stable, while being determined by HPLC, its impurity number and total impurities
Be not apparent from increase, thus compared with DO raw materials, crystal formation A has more preferable bin stability, can as DO bulk drugs stabilization
Source.
Embodiment 15
Rejection abilities of the model determination DO crystal formations A to SGLT2 is drained by rat glucose in urine.
After the high sugar of the high fat of normal SD rats is fed one month, with low dose of repeatedly intraperitoneal injection modeling (the 2 types sugar of streptozocin
Urinate disease model), determine blood-sugar content before and after modeling.It is after modeling success that modeling rat is random according to twenty-four-hour urine sugar amount and body weight
It is grouped (8/group), respectively one group blank group (giving isometric 0.5%CMC sodium solutions) and testing compound group (10mg/
kg).Fasting 16 hours before each group rat experiment.Gavage is given after DO crystal formations A0.5h made from experimental rat embodiment 1, then is filled
Stomach gives glucose (2g/kg).The urine of 0~12h periods after administration is collected, with determination of glucose oxidase each period
Urine sugar value.Experiment measures crystal formation A can induce generation 743mg glucoses in urine/200g body weight in this experiment, illustrate crystal formation A with compared with
Strong glucose in urine discharge ability.
Although present invention has been a certain degree of description, it will be apparent that, do not departing from the spirit and scope of the present invention
Under the conditions of, the appropriate change of each condition can be carried out.It is appreciated that the invention is not restricted to the embodiment, and it is attributed to right
It is required that scope, it includes the equivalent substitution of each factor.
Claims (11)
1. a kind of (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl]-D- pyrans
The crystal formation A of glucose (DO), it is characterised in that crystal formation X-ray powder diffraction characteristic absorption peak (2 θ) value is：3.80、
6.54、8.34、9.88、11.34、14.52、15.08、18.06、18.96、19.38、19.94、20.92、21.72、22.28；2θ
Measurement error is ± 0.2；
2. crystal formation A according to claim 1, it is characterised in that the X-ray powder diffraction characteristic absorption peak (2 θ) with
Interplanar distance d has following corresponding relation：
3. crystal formation A according to claim 1 or 2, it is characterised in that the X-ray powder diffraction collection such as specification is attached
Shown in Fig. 2.
4. crystal formation A according to claim 1 or 2, it is characterised in that the crystal formation differential thermal analysis curve spectrum has at 146 DEG C
There is endothermic peak.
5. a kind of (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls rings as claimed in claim 1 or 2
Hexyl) aminomethyl phenyl]-D- glucopyranoses crystal formation A preparation method, it is characterised in that by (1S) -1,6- dideoxies -1-
[4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl]-D- glucopyranoses are dissolved in a kind of good solvent,
A kind of poor solvent is slowly added to, stirring is lower to separate out crystallization, and suction filtration, drying obtain crystal formation A；The good solvent is acetic acid, third
Ketone, methanol, ethanol, isopropanol, the poor solvent are water.
6. a kind of (1S) -1,6- dideoxies -1- [4- methoxyl groups -3- (trans -4- n-propyls rings as claimed in claim 1 or 2
Hexyl) aminomethyl phenyl]-D- glucopyranoses crystal formation A preparation method, it is characterised in that by (1S) -1,6- dideoxies -1-
[4- methoxyl groups -3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl]-D- glucopyranoses are dissolved in a kind of good solvent,
A kind of poor solvent is slowly added to, stirring is lower to separate out crystallization, and suction filtration, drying obtain crystal formation A；The good solvent is acetic acid second
Ester, n-propyl acetate, isopropyl acetate, n-butyl acetate, isopropyl acetate, the poor solvent is n-hexane, hexamethylene, different
Propyl ether, ether, petroleum ether.
7. according to any described preparation methods of claim 5-6, it is characterised in that (1S) -1,6- dideoxy -1- [4-
Methoxyl group -3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl]-D- glucopyranoses and good solvent and poor solvent use
Amount ratio is 1：5~10：3~30；The ratio is quality-volume-volume ratio；Unit is g/mL/mL.
8. preparation method according to claim 7, it is characterised in that (1S) -1,6- dideoxies -1- [4- methoxyl groups -
3- (trans -4- n-propyls cyclohexyl) aminomethyl phenyl] usage ratio of-D- glucopyranoses and good solvent and poor solvent is
1：7：7.
9. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition comprising effective dose as claim 1~2 it is any
Crystal formation A and one or more pharmaceutically acceptable auxiliary materials described in.
10. pharmaceutical composition according to claim 9, it is characterised in that described pharmaceutical composition be solid orally ingestible,
Liquid oral medicine or injection；The solid orally ingestible include dispersible tablet, enteric coatel tablets, chewable tablets, oral disintegrating tablet, capsule or
Granula；The liquid oral medicine includes oral solution；The injection include injection liquid drugs injection, injection freeze-dried powder,
Big transfusion or primary infusion.
11. the crystal formation A described in claim 1 or 2 is preparing the purposes in being used to treat the medicine of diabetes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310541681.8A CN104610208B (en) | 2013-11-05 | 2013-11-05 | Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310541681.8A CN104610208B (en) | 2013-11-05 | 2013-11-05 | Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104610208A CN104610208A (en) | 2015-05-13 |
| CN104610208B true CN104610208B (en) | 2017-08-15 |
Family
ID=53144894
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310541681.8A Active CN104610208B (en) | 2013-11-05 | 2013-11-05 | Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104610208B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7273997B2 (en) * | 2019-07-05 | 2023-05-15 | 山東丹紅制薬有限公司 | Crystal forms of SGLT inhibitors and uses thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723212A (en) * | 2002-12-12 | 2006-01-18 | 安万特医药德国有限公司 | Novel aromatic fluoroglycoside derivatives, medicaments containing these compounds, and the use thereof |
| US20060189548A1 (en) * | 2005-02-23 | 2006-08-24 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted ((hetero)arylethynyl-benzyl)-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| WO2008034859A1 (en) * | 2006-09-21 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted difluorobenzyl-benzene 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 |
-
2013
- 2013-11-05 CN CN201310541681.8A patent/CN104610208B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723212A (en) * | 2002-12-12 | 2006-01-18 | 安万特医药德国有限公司 | Novel aromatic fluoroglycoside derivatives, medicaments containing these compounds, and the use thereof |
| US20060189548A1 (en) * | 2005-02-23 | 2006-08-24 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted ((hetero)arylethynyl-benzyl)-benzene derivatives, medicaments containing such compounds, their use and process for their manufacture |
| WO2008034859A1 (en) * | 2006-09-21 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Glucopyranosyl-substituted difluorobenzyl-benzene 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 |
|---|
| Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors;Shuo Zhang,等;《Chinese Chemical Letters》;20130411;第24卷(第5期);第429-432页 * |
| 含反式环己烷结构的C-葡萄糖苷类SGLT2抑制剂的设计、合成与降血糖活性研究;邵华，等;《有机化学》;20111231;第31卷(第6期);第836-842页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104610208A (en) | 2015-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100384830C (en) | Derivative of cyclo membranousol kind and application thereof | |
| CN106916177B (en) | A kind of deuterated dipeptide boronic acid or its ester type compound and its synthetic method and purposes | |
| CN101585859B (en) | Novel scutellarin derivative as well as preparation method and pharmaceutical composition thereof | |
| JP2021521237A (en) | Methods for preparing regulators of P300 and / or CBP | |
| CN104017031A (en) | Hypoglycemic drug and composition | |
| CN103044395A (en) | Desloratadine-containing amino acid derivative as well as preparation method and application thereof | |
| CN104031098A (en) | Hypoglycemic medicine | |
| CN100554263C (en) | The preparation method of strontium ranelate heptahydrate | |
| CN105801568B (en) | One maleate crystal form of Afatinib and preparation method thereof and pharmaceutical composition | |
| CN101597272B (en) | Sodium salt compound of Iguratimod, preparation method thereof and pharmaceutical use thereof | |
| CN105001195B (en) | Novel crystal forms of R (+) lipoic acid L lysine salts and preparation method thereof | |
| CN104045615B (en) | (1S) crystal form A and its preparation method and application of-1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1,6-dideoxy-D-Glucose | |
| CN104610208B (en) | Crystal formation A of (1S) 1,6 dideoxy 1 [4 methoxyl group 3 (trans 4 n-propyl cyclohexyl) aminomethyl phenyl] D glucopyranoses and its preparation method and application | |
| CN104861002A (en) | 3,6-anhydroglucose structure-containing phenyl C-glucoside derivatives and their preparation method and use | |
| CN104693192A (en) | Crystal form A of compound as well as preparation method and application thereof | |
| CN101429154B (en) | Anhydrous alvimopan and medicament composition thereof | |
| CN110840880B (en) | Application of puerarin derivative in preparing anticancer medicine and medicine for treating cancer | |
| CN104693190B (en) | Crystal form B of compound as well as preparation method and application thereof | |
| CN102675378A (en) | C-glucoside derivative containing cyclopropane structure and method and application of C- glucoside derivative | |
| CN102351835B (en) | Mangiferin aglycone crystal forms, and composition, preparation method and application thereof | |
| CN104045614B (en) | (1S) crystal C and its preparation method and application of-1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1,6-dideoxy-D-Glucose | |
| CN113651770A (en) | Novel crystal form of epalrestat, preparation method and application thereof | |
| CN104761523B (en) | Phenyl C glucoside derivatives, Preparation Method And The Use containing 3 oxo glucose structures | |
| CN104045613B (en) | (1S) the cocrystallization I and its preparation method and application of-1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1,6-dideoxy-D-Glucose and L-PROLINE | |
| CN104230932A (en) | Matrine derivatives as well as preparation method and application of matrine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Applicant after: TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH CO., LTD. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Applicant before: Tianjin Institute of Pharmaceutical Research |
|
| COR | Change of bibliographic data | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210806 Address after: 300301 No. 308, Huiren Road, Binhai Science Park, Binhai high tech Zone, Tianjin Binhai New Area, Tianjin Patentee after: Tianjin Tiancheng new drug evaluation Co.,Ltd. Address before: 300193 Tianjin City, Nankai District Anshan West Road No. 308 Patentee before: Tianjin Institute of Pharmaceutical Research Co.,Ltd. |
|
| TR01 | Transfer of patent right |