Crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((
The invention relates to crystalline forms of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, to a method for the preparation thereof, as well as to the use thereof for preparing medicaments.
1. A crystalline form of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-(R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene.
2. A crystalline form I of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 17.86, 18.01 and 19.24 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation.
3. A crystalline form I according to claim 2 , wherein the X-ray powder diffraction pattern further comprises peaks at 24.05 and 24.51 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation.
4. 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene wherein at least 50% of said substance is present in the form of the crystalline form I in accordance with claim 2 .
5. 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene wherein at least 50% of said substance is present in the form of the crystalline form I in accordance with claim 3 .
6. A crystalline form II of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 15.88, 18.36, 18.87 and 19.20 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation.
7. The crystalline form II according to claim 6 , wherein the X-ray powder diffraction pattern further comprises peaks at 20.36 and 23.64 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation.
8. 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene wherein at least 50% of said substance is present in the form of the crystalline form II in accordance with claim 6 .
9. 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene wherein at least 50% of said substance is present in the form of the crystalline form II in accordance with claim 7 .
10. A pharmaceutical composition comprising a crystalline form in accordance with claim 1 .
11. A pharmaceutical composition comprising a crystalline form in accordance with claim 2 .
12. A pharmaceutical composition comprising a crystalline form in accordance with claim 6 .
13. A method of treating a metabolic disorder selected from the group consisting of:
type 1 and type 2 diabetes mellitus, complications of diabetes, metabolic acidosis or ketosis, reactive hypoglycaemia, hyperinsulinaemia, glucose metabolic disorder, insulin resistance, metabolic syndrome, dyslipidaemias of different origins, atherosclerosis and related diseases, obesity, high blood pressure, chronic heart failure, oedema and hyperuricaemia,
said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 .
14. A method of treating a metabolic disorder selected from the group consisting of:
type 1 and type 2 diabetes mellitus, complications of diabetes, metabolic acidosis or ketosis, reactive hypoglycaemia, hyperinsulinaemia, glucose metabolic disorder, insulin resistance, metabolic syndrome, dyslipidaemias of different origins, atherosclerosis and related diseases, obesity, high blood pressure, chronic heart failure, oedema and hyperuricaemia,
said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 2 .
15. A method of treating a metabolic disorder selected from the group consisting of:
type 1 and type 2 diabetes mellitus, complications of diabetes, metabolic acidosis or ketosis, reactive hypoglycaemia, hyperinsulinaemia, glucose metabolic disorder, insulin resistance, metabolic syndrome, dyslipidaemias of different origins, atherosclerosis and related diseases, obesity, high blood pressure, chronic heart failure, oedema and hyperuricaemia,
said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 6 .
16. A method of inhibiting the sodium-dependent glucose cotransporter SGLT2 said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 .
17. A method of inhibiting the sodium-dependent glucose cotransporter SGLT2 said method comprised of the steps of administering to a patient in need thereof a therepuetically effective amount of a compound according to claim 2 .
18. A method of inhibiting the sodium-dependent glucose cotransporter SGLT2 said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 6 .
19. A method of treating degeneration of pancreatic beta cells and/or for improving the functionality of pancreatic beta cells said method comprised of the steps of administering to a patient in need therof a therapeutically effective amount of a compound according to claim 1 .
20. A method of treating degeneration of pancreatic beta cells and/or for improving the functionality of pancreatic beta cells said method comprised of the steps of administering to a patient in need therof a therapeutically effective amount of a compound according to claim 2 .
21. A method of treating degeneration of pancreatic beta cells and/or for improving the functionality of pancreatic beta cells said method comprised of the steps of administering to a patient in need therof a therapeutically effective amount of a compound according to claim 6 .
22. A method for making the crystalline form I in accordance with claim 2 , said method comprising the following steps: (a) dissolving the compound 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene in a solvent or a mixture of solvents to form a saturated or nearly saturated solution, with the proviso that the compound and/or said solvent or mixture of solvents contain an amount of H 2 O which is at least the quantity required to form a monohydrate of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene; (b) storing the solution to precipitate the crystalline form I in accordance with claim 2 out of solution and thus to yield a suspension; (c) isolating the precipitate from the suspension; and (d) drying the precipitate until any excess of said solvent or mixture of solvents has been removed.
23. A method for making the crystalline form I in accordance with claim 3 , said method comprising the following steps: (a) dissolving the compound 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene in a solvent or a mixture of solvents to form a saturated or nearly saturated solution, with the proviso that the compound and/or said solvent or mixture of solvents contain an amount of H 2 O which is at least the quantity required to form a monohydrate of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene; (b) storing the solution to precipitate the crystalline form I in accordance with claim 3 out of solution and thus to yield a suspension; (c) isolating the precipitate from the suspension; and (d) drying the precipitate until any excess of said solvent or mixture of solvents has been removed.
24. A method for making the crystalline form II in accordance with claim 6 , said method comprising the following step: (a) drying a crystalline form I of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 17.86, 18.01 and 19.24 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation, at a temperature in a range between equal to or greater than 80° C. and smaller than the lower melting point of said crystalline forms I and II or at a lower temperature under reduced pressure.
25. A method for making the crystalline form II in accordance with claim 7 , said method comprising the following step: (a) drying a crystalline form I of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 17.86, 18.01 and 19.24 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation, at a temperature in a range between equal to or greater than 80° C. and smaller than the lower melting point of said crystalline forms I and II or at a lower temperature under reduced pressure.
26. A method for making the crystalline form II in accordance with claim 6 , said method comprising the following step: (a) drying a crystalline form I of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 17.86, 18.01, 19.24, 24.05 and 24.51 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation, at a temperature in a range between equal to or greater than 80° C. and smaller than the lower melting point of said crystalline forms I and II or at a lower temperature under reduced pressure.
27. A method for making the crystalline form II in accordance with claim 7 , said method comprising the following step: (a) drying a crystalline form I of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene having an X-ray powder diffraction pattern that comprises peaks at 17.86, 18.01 19.24, 24.05 and 24.51 degrees 2Θ±0.05 degrees 2Θ, wherein said X-ray powder diffraction pattern is made using CuK α1 radiation, at a temperature in a range between equal to or greater than 80° C. and smaller than the lower melting point of said crystalline forms I and II or at a lower temperature under reduced pressure.