Claims
- 1. 4-Amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline mesylate of the formula
- 2. The mesylate salt as claimed in claim 1, characterised in that it exhibits an endothermic thermal event at about 279° C. during differential scanning calorimetry.
- 3. The mesylate salt as claimed in claim 1 or claim 2, characterised by a powder X-ray diffraction pattern obtained by irradiation with copper K-alpha1 X-rays of wavelength 1.5406 Å, having the following main peaks:
- 4. A substantially pure anhydrous crystalline free base form of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline.
- 5. A free base form as claimed in claim 4, characterised in that it exhibits an endothermic thermal event at about 198° C. during differential scanning calorimetry (designated Form A).
- 6. A free base form as claimed in claim 4 or claim 5, characterised by a powder X-ray diffraction pattern obtained by irradiation with copper K-alpha1 X-rays of wavelength 1.5406 Å, having the following main peaks:
- 7. A free base form as claimed in claim 4, characterised in that it exhibits an endothermic thermal event at about 218° C. during differential scanning calorimetry (designated Form B).
- 8. A free base form as claimed in claim 4 or claim 7, characterised by a powder X-ray diffraction pattern obtained by irradiation with copper K-alpha1 X-rays of wavelength 1.5406 Å, having the following main peaks:
- 9. A free base form as claimed in claim 4, characterised in that it exhibits an endothermic thermal event at about 147° C. during differential scanning calorimetry (designated Form C).
- 10. A free base form as claimed in claim 4 or claim 9, characterised by a powder X-ray diffraction pattern obtained by irradiation with copper K-alpha1 X-rays of wavelength 1.5406 Å, having the following main peaks:
- 11. A free base form as claimed in claim 4, characterised in that it exhibits an endothermic thermal event at about 229° C. (designated Form E).
- 12. A free base form as claimed in claim 4 or claim 11, characterised by a powder X-ray diffraction pattern obtained by irradiation with copper K-alpha1 X-rays of wavelength 1.5406 Å, having the following main peaks:
- 13. A pharmaceutical formulation containing 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline in the form of the anhydrous free base or the mesylate salt, as defined in any one of claims 1 to 12, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
- 14. 4-Amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline in the form of the anhydrous free base or the mesylate salt, as defined in any one of claims 1 to 12, for use as a pharmaceutical.
- 15. The use of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline in the form of the anhydrous free base or the mesylate salt, as defined in any one of claims 1 to 12, in the manufacture of a medicament for the treatment of benign prostatic hyperplasia.
- 16. A method of treatment of benign prostatic hyperplasia, which comprises administering a therapeutically effective amount of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline in the form of the anhydrous free base or the mesylate salt, as defined in any one of claims 1 to 12, to a patient suffering from such a disorder.
- 17. A process for the preparation of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl) quinazoline mesylate, as defined in claim 1, which comprises the addition of methanesulphonic acid to a suspension or solution of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline of the formula
- 18. A process as claimed in claim 17, wherein the solution of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)-quinazoline is maintained at a temperature above room temperature before the addition of the methanesulphonic acid.
- 19. A process as claimed in claim 17 or claim 18, wherein the solvent used is a mixture of butanone and water.
- 20. A process as claimed in any one of claims 17, 18 and 19, wherein the solvent is a 10:1 by volume mixture of butanone and water.
- 21. A process as claimed in claim 19 or claim 20, comprising the steps of:
(a) heating a suspension of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline in butanone/water to reflux; (b) adding butanone/water until a solution is achieved; (c) cooling the solution; (d) adding methanesulfonic acid; and (e) collecting the resulting solid by filtration.
- 22. A process as claimed in any one of claims 17 to 21, wherein the 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline is present as Form E, as defined in claim 11 or claim 12.
Priority Claims (2)
Number |
Date |
Country |
Kind |
GB0005200.1 |
Mar 2000 |
GB |
|
GB 0015900.4 |
Jun 2000 |
GB |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. provisional application No. 60/192,912, filed Mar. 29, 2000 and 60/218,188, filed Jul. 14, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60192912 |
Mar 2000 |
US |
|
60218188 |
Jul 2000 |
US |