CN105111207A - Cyclopropanecarboxamide derivative D crystal form and preparation method thereof - Google Patents
Cyclopropanecarboxamide derivative D crystal form and preparation method thereof Download PDFInfo
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- CN105111207A CN105111207A CN201510599172.XA CN201510599172A CN105111207A CN 105111207 A CN105111207 A CN 105111207A CN 201510599172 A CN201510599172 A CN 201510599172A CN 105111207 A CN105111207 A CN 105111207A
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- cyclopropanecarbonyl
- sulfonamide derivatives
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- jak
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention provides a cyclopropanecarboxamide derivative D crystal form (please see the formula in the specification). According to the XRPD map of the cyclopropanecarboxamide derivative D crystal form, diffraction peaks exist at the positions of 2theta=7.458, 8.879, 12.319, 14.88, 16.742, 17.699, 18.538, 19.64, 20.62, 21.041, 22.902, 23.621, 24.779, 25.901, 26.801, 27.842, 28.698, 29.981, 31.539 and 32.481, wherein the error range of the 2theta values is +/-0.2. The cyclopropanecarboxamide derivative D crystal form has good high-temperature stability and illumination stability and also has low moisture absorption performance, can be applied to drugs for treating or preventing inflammations where JAK takes part in, autoimmune diseases, proliferative diseases, transplant rejection reaction, congenital cartilage deformity or diseases caused by IL6 hypersecretion, and has good bioavailability, and meanwhile the provided qualitative and quantitative information has great significance for further study of the curative effect of the kind of solid drugs.
Description
Technical field
The present invention relates to a kind of polymorphic of the cyclopropanecarbonyl sulfonamide derivatives as JAK inhibitor, particularly, relate to a kind of cyclopropanecarbonyl sulfonamide derivatives form D and preparation method thereof.
Background technology
JAK and Janus kinases (JanusKinase) are a kind of non-receptor type tyrosine protein kinases, are also the Tyrosylprotein kinases of the non-transmembrane of a class.This is because JAK can phosphorylation cytokine receptor combined with it, again can the multiple signaling molecule containing specific SH2 structural domain of phosphorylation.JAK protein family comprises 4 members altogether: JAK1, JAK2, JAK3 and TYK2, they structurally have 7 JAK homeodomain (JAKhomologydomain, JH), wherein JH1 structural domain is kinases district, JH2 structural domain is "false" kinases district, JH6 and JH7 is receptorbinding region.
TYK2 is the potential target spot of Immunoinflammatory Disorders, rejects research confirmation (LevyD. and LoomisC., NewEnglandJournalofMedicine357 (2007) 1655-1658 page) by people's genetics and mouse.
JAK1 is the novel targets in Immunoinflammatory Disorders field.JAK1 and other JAK to be mixed dimerization, the pro-inflammatory signals conduction driven with the transducer cell factor.Therefore, expection suppress JAK1 and or other JAK have treatment benefit for the disease that a series of inflammatory conditions and other signal transductions of being mediated by JAK drive.
Cyclopropanecarbonyl sulfonamide derivatives, chemical name N-[5-[4-[(1,1-dioxo-4-thio-morpholinyl) methyl] phenyl] [1,2,4] triazolo [1,5-A] pyridine-2-base] cyclopropane carboxamide, shown in (I)
Be a kind of JAK class inhibitor compound, can be used for the disease for the treatment of or preventing the inflammation of JAK participation, autoimmune disorder, proliferative disease, graft-rejection and congenital cartilage deformity or causing with IL6 supersecretion.In Chinese invention patent CN102105471 (WO2010/010190), disclose the synthetic method of this compound; In Chinese invention patent CN102482273 (WO2010/149769), disclose the purposes of cyclopropanecarbonyl sulfonamide derivatives.Repeating the preparation method of above-mentioned patent, obtain compound powder, is amorphous state after testing.As is known to the person skilled in the art, all have higher solubleness and dissolution rate than crystal formation although amorphous in most of occasion, it is unstable, and water absorbability is strong, easily transfers stable crystal formation to.Therefore, the amorphous problem that there is processing stability and package stability, and in process of production, the loose density of amorphous particle is less, surface free energy is high, a series of formulation problems such as also easily cause cohesion, poor fluidity, recoverable deformation strong, has a strong impact on the clinical drug use value of amorphous cyclopropanecarbonyl sulfonamide derivatives.
As everyone knows, same medicine, crystal formation is different, also difference may be there is in its bioavailability, its stability, mobility, compressibility also may be different in addition, and the application of these physico-chemical properties on medicine produces certain impact, thus affects the curative effect of medicine.Therefore, need the crystal formation of the cyclopropanecarbonyl sulfonamide derivatives with superior physiochemical properties, it can advantageously use in medicine processing and pharmaceutical composition.The new crystal of the cyclopropanecarbonyl sulfonamide derivatives of the present invention's development has no report.
Summary of the invention
Problem to be solved by this invention be existing cyclopropanecarbonyl sulfonamide derivatives unstable, water absorbability and easily transfer to the problems such as stable crystal formation be unfavorable for medicine processing and use in pharmaceutical composition, the new crystal of cyclopropanecarbonyl sulfonamide derivatives, the effectiveness study for solid pharmaceutical provides the problem of more qualitative, quantitative information.
In order to solve the problems of the technologies described above, the invention provides a kind of new crystal formation (hereinafter referred to as " cyclopropanecarbonyl sulfonamide derivatives form D ") of cyclopropanecarbonyl sulfonamide derivatives, shown in (I).
Its XRPD collection of illustrative plates in 2 θ=7.458,8.879,12.319,14.88,16.742,17.699,18.538,19.64,20.62,21.041,22.902,23.621,24.779,25.901,26.801,27.842,28.698,29.981,31.539, there is diffraction peak at 32.481 places, wherein 2 θ value limit of error are ± 0.2.
According to cyclopropanecarbonyl sulfonamide derivatives form D of the present invention, there is the XRPD collection of illustrative plates substantially the same with Figure of description Fig. 1.
Present invention also offers a kind of method preparing cyclopropanecarbonyl sulfonamide derivatives form D, comprise the following steps: the ratio with 1:150 ~ 1:250g/mL in cyclopropanecarbonyl sulfonamide derivatives adds organic solvent, at room temperature suspend, then filter, vacuum-drying thus obtain the cyclopropanecarbonyl sulfonamide derivatives form D of off-white powder.
In certain embodiments, described organic solvent is that any one solvent in alcohols or two or more solvent are with the mixed solvent of arbitrary proportion.
In some preferred embodiments, described alcohol organic solvent is methyl alcohol or ethanol.
Those of ordinary skill in the art according to its knowledge and experience, can adjust the consumption of the inventive method agents useful for same, and comprise and scale up or reduce raw material dosage and adjustment solvent load, the scheme of these adjustment is also contained in method of the present invention.
In above-mentioned steps, the ratio of cyclopropanecarbonyl sulfonamide derivatives and solvent is preferably 1:200g/mL.
The compound with cyclopropanecarbonyl sulfonamide derivatives form D of the present invention is used for the treatment of and the Tyrosylprotein kinase of autoimmune disorder (JAK) inhibitor.JAK is the kinase whose one of TYR, and JAK belongs to and participates in inflammation, autoimmune disorder, proliferative disease, graft-rejection and congenital cartilage deformity, or the disease caused with IL6 supersecretion.Compound of the present invention suppresses JAK1 and JAK2.
Therefore, the invention provides the purposes of cyclopropanecarbonyl sulfonamide derivatives form D in the medicine for the preparation of suppression JAK; And the purposes in the inflammation participated in for the preparation for the treatment of or prevention JAK, autoimmune disorder, proliferative disease, graft-rejection and congenital cartilage deformity or the medicine of disease that causes with IL6 supersecretion.
Present invention also offers pharmaceutical composition, it comprises according to cyclopropanecarbonyl sulfonamide derivatives form D of the present invention and one or more pharmaceutically acceptable carrier, vehicle or thinner.
In some embodiments of the invention, aforementioned pharmaceutical compositions comprises other therapeutical agent further, described therapeutical agent be selected from chemotherapy or antiproliferative, anti-inflammatory agent, immunomodulatory or immunosuppressor, neurotrophic factor, be used for the treatment of autoimmune disorder promoting agent, be used for the treatment of proliferative disease promoting agent, be used for the treatment of graft-rejection promoting agent, for congenital cartilage deformity promoting agent or be used for the treatment of the promoting agent of the disease caused with IL6 supersecretion.
According to cyclopropanecarbonyl sulfonamide derivatives form D of the present invention, there is outstanding high-temperature stability, light durability and agent of low hygroscopicity, be conducive to medicine processing and use in pharmaceutical composition, apply in the inflammation that can participate in treatment or prevention JAK, autoimmune disorder, proliferative disease, graft-rejection and congenital cartilage deformity or the medicine of disease that causes with IL6 supersecretion, and there is good bioavailability, the qualitative, quantitative information simultaneously provided, has great importance to the curative effect studying this type of solid pharmaceutical further.
Accompanying drawing explanation
Fig. 1 is the XRPD collection of illustrative plates of cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention.
Fig. 2 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention five days high-temperature stability XRPD collection of illustrative plates.
Fig. 3 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention five days high humidity stability XRPD collection of illustrative plates.
Fig. 4 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention five days light durability XRPD collection of illustrative plates.
Fig. 5 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention ten days high-temperature stability XRPD collection of illustrative plates.
Fig. 6 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention ten days high humidity stability XRPD collection of illustrative plates.
Fig. 7 is cyclopropanecarbonyl sulfonamide derivatives form D provided by the invention ten days light durability XRPD collection of illustrative plates.
Fig. 8 is the unbodied XRPD collection of illustrative plates of existing cyclopropanecarbonyl sulfonamide derivatives.
Embodiment
From detailed description hereafter, above-mentioned aspect of the present invention and other aspects of the present invention will be obvious.
The preparation of embodiment 1 to 2 cyclopropanecarbonyl sulfonamide derivatives form D
Take 500mg cyclopropanecarbonyl sulfonamide derivatives raw material in container, add the solvent (analytical pure) in 100mL table 1 respectively, 35 DEG C suspend 48 hours, obtain off-white powder after filtration, vacuum-drying.Weigh and calculate its yield.
The preparation of table 1 cyclopropanecarbonyl sulfonamide derivatives form D
| Embodiment | Solvent | Yield |
| 1 | Methyl alcohol | 66％ |
| 2 | Ethanol | 69％ |
Embodiment 3. characterizes cyclopropanecarbonyl sulfonamide derivatives form D by XRPD figure
The measurement of X-ray powder diffraction (XRPD) collection of illustrative plates, the multifunctional assembled X-ray diffractometer of RigakuUltimaIV model is used to carry out, concrete Information Monitoring is as follows: Cu anode (40kV, 40mA), sweep velocity 20 °/minute, sweep limit (2 θ scope) 3 ~ 45 °, scanning step 0.02, slit width 0.01.Slide glass is adopted directly to process sample in test panel compacting.Thereafter XRPD collection of illustrative plates all adopts similar measuring method.
Measure the XRPD collection of illustrative plates of cyclopropanecarbonyl sulfonamide derivatives form D prepared by method according to embodiment 1, in 2 θ=7.458,8.879,12.319,14.88,16.742,17.699,18.538,19.64,20.62,21.041,22.902,23.621,24.779,25.901,26.801,27.842,28.698,29.981,31.539, there is diffraction peak at 32.481 places, as shown in Figure 1.Wherein 2 θ value limit of error are ± 0.2.After testing, 2 θ value limit of error also can be ± 0.15.The cyclopropanecarbonyl sulfonamide derivatives form D that according to embodiment 2 prepared by method, shown in its XRPD collection of illustrative plates with accompanying drawing 1, collection of illustrative plates is substantially identical.
It will be understood by those skilled in the art that these diffraction peaks do not represent the detailed situation of diffraction peak shown by cyclopropanecarbonyl sulfonamide derivatives form D.2 θ values of X-ray powder diffraction pattern be can along with machine and along with the change in sample preparation and batch between change and slightly changing, the value quoted is not considered as absolute value.It will also be appreciated that the relative intensity at peak may become with orientation effect, the intensity shown in XRD trace therefore contained by the present invention is exemplary, and is not used in and definitely compares.
The high-temperature stability of embodiment 4. cyclopropanecarbonyl sulfonamide derivatives form D is investigated
Cyclopropanecarbonyl sulfonamide derivatives form D sample is placed in 60 DEG C of baking ovens, after 5 days and 10 days, sample is taken out and carry out XRPD test (as shown in Figure 2 and Figure 5), to investigate the stability of crystal form of sample to temperature.Result shows, under hot conditions, crystal formation D sample is stablized.
The high humidity study on the stability of embodiment 5. cyclopropanecarbonyl sulfonamide derivatives form D
Under cyclopropanecarbonyl sulfonamide derivatives form D sample is placed in 92.5% humidity condition, after 5 days and 10 days, sample is taken out and carry out XRPD test (as shown in Figure 3 and Figure 6), to investigate the stability of crystal form of sample to temperature.Test result illustrates in table 2.Result shows, under super-humid conditions, crystal formation D sample stability is general.
The high humidity stability of table 2 cyclopropanecarbonyl sulfonamide derivatives form D
| Sample | Color | Gain in weight |
| Form D | Off-white color | 0.00％ |
| Form D after five days | Off-white color | 6.66％ |
| Form D after ten days | Off-white color | 6.78％ |
The light durability of embodiment 6 cyclopropanecarbonyl sulfonamide derivatives form D is investigated
Under cyclopropanecarbonyl sulfonamide derivatives form D sample is placed in 4500lux intensity of illumination, after 5 days and 10 days, sample is taken out and carry out XRPD test (as shown in figs. 4 and 7), to investigate the stability of crystal form of sample to temperature.Result shows, under illumination condition, crystal formation D sample is stablized.
The unbodied preparation of embodiment 7 cyclopropanecarbonyl sulfonamide derivatives
Because the synthetic method adopted in the synthetic method that adopts in Chinese invention patent CN102482273 and Chinese invention patent CN102105471 is completely the same, therefore according to the two kinds of methods recorded in Chinese invention patent CN102482273, cyclopropanecarbonyl sulfonamide derivatives is prepared.After obtaining the organic layer containing cyclopropanecarbonyl sulfonamide derivatives, by organic layer through anhydrous MgSO
4dry also vacuum-evaporation.By obtaining finalization compound after flash chromatography or preparative HPLC purifying.
As shown in Figure 8, measure through XRPD, the final product of gained is amorphous samples.
Embodiment 8 cyclopropanecarbonyl sulfonamide derivatives form D and unbodied solubleness compare
In 20mL sample bottle, add excessive form D and amorphous powder respectively, add appropriate water, shake after 24 hours under room temperature, sampling detects solubleness.The water solubility of crystal formation D is 55.26 μ g/mL, and unbodied water solubility is 100.32 μ g/mL.
As can be seen from result, cyclopropanecarbonyl sulfonamide derivatives form D of the present invention has low solubleness more amorphous than cyclopropanecarbonyl sulfonamide derivatives.
Those skilled in the art should understand, although for illustrative purposes, this document describes the specific embodiment of the present invention, can carry out various amendment and without departing from the spirit and scope of the present invention to it.Therefore, the specific embodiment of the present invention and embodiment should not be considered as limiting the scope of the invention.The present invention is only by the restriction of claims.The all documents quoted in the application are all intactly incorporated to herein as a reference.
Claims (10)
1. a cyclopropanecarbonyl sulfonamide derivatives form D for formula (I), is characterized in that,
Its XRPD collection of illustrative plates in 2 θ=7.458,8.879,12.319,14.88,16.742,17.699,18.538,19.64,20.62,21.041,22.902,23.621,24.779,25.901,26.801,27.842,28.698,29.981,31.539, there is diffraction peak at 32.481 places, wherein 2 θ value limit of error are ± 0.2.
2. cyclopropanecarbonyl sulfonamide derivatives form D as claimed in claim 1, it is characterized in that, it has the XRPD collection of illustrative plates substantially the same with Figure of description Fig. 1.
3. prepare the method for cyclopropanecarbonyl sulfonamide derivatives form D as claimed in claim 1 or 2, it is characterized in that, comprise the following steps: the ratio with 1:150 ~ 1:250g/mL in cyclopropanecarbonyl sulfonamide derivatives adds organic solvent, at room temperature suspend, then filter, vacuum-drying thus obtain the cyclopropanecarbonyl sulfonamide derivatives form D of off-white powder.
4. method as claimed in claim 3, is characterized in that, described organic solvent is that any one solvent in alcohols or two or more solvent are with the mixed solvent of arbitrary proportion.
5. method as claimed in claim 4, is characterized in that,
Described alcohol organic solvent is methyl alcohol or ethanol.
6. the purposes of cyclopropanecarbonyl sulfonamide derivatives form D as claimed in claim 1 or 2 in the medicine for the preparation of suppression JAK.
7. the purposes of cyclopropanecarbonyl sulfonamide derivatives form D as claimed in claim 1 or 2 in the inflammation participated in for the preparation for the treatment of or prevention JAK, autoimmune disorder, proliferative disease, graft-rejection and congenital cartilage deformity or the medicine of disease that causes with IL6 supersecretion.
8. pharmaceutical composition, it comprises cyclopropanecarbonyl sulfonamide derivatives form D as claimed in claim 1 or 2.
9. pharmaceutical composition as claimed in claim 8, it also comprises one or more pharmaceutically acceptable carrier, vehicle or thinners.
10. pharmaceutical composition as claimed in claim 8, it comprises other therapeutical agent further, described therapeutical agent be selected from chemotherapy or antiproliferative, anti-inflammatory agent, immunomodulatory or immunosuppressor, neurotrophic factor, be used for the treatment of autoimmune disorder promoting agent, be used for the treatment of proliferative disease promoting agent, be used for the treatment of graft-rejection promoting agent, for congenital cartilage deformity promoting agent or be used for the treatment of the promoting agent of the disease caused with IL6 supersecretion.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018024236A1 (en) * | 2016-08-03 | 2018-02-08 | 苏州科睿思制药有限公司 | Novel crystal form of jak1-selective inhibitor, and manufacturing method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102105471A (en) * | 2008-07-25 | 2011-06-22 | 加拉帕戈斯股份有限公司 | Novel compounds useful for the treatment of degenerative and inflammatory diseases |
| CN102482273A (en) * | 2009-06-26 | 2012-05-30 | 加拉帕戈斯股份有限公司 | 5-phenyl-[1,2,4 ]triazolo[1,5-a]pyridin-2-yl carboxamides as jak inhibitors |
| WO2015117981A1 (en) * | 2014-02-07 | 2015-08-13 | Galapagos Nv | Novel salts and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| WO2015117980A1 (en) * | 2014-02-07 | 2015-08-13 | Galapagos Nv | Pharmaceutical compositions for the treatment of inflammatory disorders |
-
2015
- 2015-09-18 CN CN201510599172.XA patent/CN105111207B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102105471A (en) * | 2008-07-25 | 2011-06-22 | 加拉帕戈斯股份有限公司 | Novel compounds useful for the treatment of degenerative and inflammatory diseases |
| CN102482273A (en) * | 2009-06-26 | 2012-05-30 | 加拉帕戈斯股份有限公司 | 5-phenyl-[1,2,4 ]triazolo[1,5-a]pyridin-2-yl carboxamides as jak inhibitors |
| WO2015117981A1 (en) * | 2014-02-07 | 2015-08-13 | Galapagos Nv | Novel salts and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| WO2015117980A1 (en) * | 2014-02-07 | 2015-08-13 | Galapagos Nv | Pharmaceutical compositions for the treatment of inflammatory disorders |
Non-Patent Citations (1)
| Title |
|---|
| CHRISTEL J.MENET ET AL.: ""Triazolopyridines as Selective JAK1 Inhibitors:From Hit Identification to GLPG0634"", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018024236A1 (en) * | 2016-08-03 | 2018-02-08 | 苏州科睿思制药有限公司 | Novel crystal form of jak1-selective inhibitor, and manufacturing method and application thereof |
| CN109476662A (en) * | 2016-08-03 | 2019-03-15 | 苏州科睿思制药有限公司 | A kind of novel crystal forms and its preparation method and application of JAK1 selective depressant |
| US10633376B2 (en) | 2016-08-03 | 2020-04-28 | Crystal Pharmaceutical (Suzhou) Co., Ltd. | Crystalline forms of JAK1-selective inhibitor, processes for preparation and use thereof |
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