Forms of methyl {4,6-diamino-2-[1(2-fluorobenzyl)-1H-pyrazolo[3-4-b]pyridino-3-yl]pyrimidino-5-yl}methyl carbamate
This present invention relates to forms of methyl {4.6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3.4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate comprising its Modification I. Modification II. mono-DMSO solvate. sesqui-DMSO solvate and ¼-ethyl acetate solvate.
1. A compound of the formula (I)
in crystalline form having an X-Ray powder diffractogram comprising at least three peak maxima of the 2 Theta angle selected from 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
2. The compound of claim 1 , wherein the X-ray powder diffractogram comprises peak maxima of the 2 Theta angle of 6.7, 9.1, 14.4, 17.8, and 25.6.
3. The compound of claim 1 , wherein the X-Ray powder diffractogram comprises peak maxima of the 2 Theta angle of 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
4. The compound of claim 1 , wherein the ten major reflexes of the X-ray powder diffractogram have peak maxima of the 2 Theta angle of 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
5. The compound of claim 1 , wherein the X-ray powder diffractogram is recorded using Cu K alpha 1 radiation having a wavelength of 1.5406 Å.
6. The compound of claim 2 , wherein the X-ray powder diffractogram is recorded using Cu K alpha 1 radiation having a wavelength of 1.5406 Å.
7. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a compound of the formula (I)
and a pharmaceutically acceptable carrier, in which more than 90 percent by weight relative to the total weight of all forms of the compound of formula (I) in the composition is in crystalline form of Modification (I).
9. The pharmaceutical composition of claim 8 , wherein the compound of the formula (I) is characterized by an X-Ray powder diffractogram comprising at least three peak maxima of the 2 Theta angle selected from 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
10. The pharmaceutical composition of claim 9 , wherein the X-ray powder diffractogram comprises peak maxima of the 2 Theta angle of 6.7, 9.1 and 17.8.
11. The pharmaceutical composition of claim 9 , wherein the X-ray powder diffractogram comprises peak maxima of the 2 Theta angle of 6.7, 9.1, 14.4, 17.8, and 25.6.
12. The pharmaceutical composition of claim 9 , wherein the X-ray powder diffractogram comprises peak maxima of the 2 Theta angle of 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
13. The pharmaceutical composition of claim 8 , in which more than 95 percent by weight relative to the total weight of all forms of the compound of formula (I) in the composition is in crystalline form of Modification (I).
14. A method for the treatment of pulmonary arterial hypertension comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.
15. A method for the treatment of pulmonary hypertension associated with thromboembolism (CTEPH) comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.
16. A method for the treatment of pulmonary arterial hypertension comprising administering a therapeutically effective amount of a compound of the formula (I)
in the crystalline form of Modification I to a patient in need thereof.
17. The method of claim 16 , wherein the compound of the formula (I) has an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1 and 17.8.
18. The method of claim 16 comprising administering the compound of formula (I) in the crystalline form of Modification I and an endothelin antagonist to the patient in need thereof.
19. The method of claim 16 , wherein the compound of the formula (I) has an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.
20. A method for the treatment of pulmonary hypertension associated with thromboembolism (CTEPH) comprising administering a therapeutically effective amount of a compound of the formula (I)
in the crystalline form of Modification I to a patient in need thereof.
21. The method of claim 20 , wherein the compound of the formula (I) has an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1 and 17.8.
22. The method of claim 20 , wherein the compound of formula (I) has an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3.