11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-maleate salt
View Patent ↗The present invention relates to certain salts of a 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26triaza-tetra-cyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (Compound I) which have been found to have improved properties. In particular the present invention relates to the maleate salt of this compound. The invention also relates to pharmaceutical compositions containing this salt and methods of use of the salt in the treatment of certain medical conditions.
1. A crystalline maleate salt of 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo [19.3.1.1 (2,6)0.1(8,12)]heptacosa-1(25), 2(26),3,5,8,10,12(27), 16,21,23-decaene which shows on X-ray diffraction a peak on the 2theta scale at 17.5°±0.5°.
2. A salt according to claim 1 wherein the salt is the 1:1 salt.
3. A salt according to claim 1 which shows on X-ray diffraction a peak on the 2theta scale at 21.3°±0.5°.
4. A salt according to claim 1 which shows on X-ray diffraction at least two peaks on the 2theta scale selected from the group consisting of 8.3°±0.5°, 8.8°±0.5°, 16.9°±0.5°, 17.5°±0.5°, 19.0°±0.5°, 21.3°±0.5°, 23.8°±0.5°, 25.3°±0.5°, 25.8°±0.5° and 26.8°±0.5°.
5. A salt according to claim 1 which shows on X-ray diffraction at least 4 peaks on the 2theta scale selected from the group consisting of 8.3 °±0.5°, 8.8°±0.5°, 16.9°±0.5°, 17.5°±0.5°, 19.0°±0.5°, 21.3°±0.5°, 23.8°±0.5°, 25.3°±0.5°, 25.8°±0.5° and 26.8°±0.5°.
6. A salt according to claim 1 which shows on X-ray diffraction at least 6 peaks on the 2theta scale selected from the group consisting of 8.3°±0.5°, 8.8°±0.5°, 16.9°±0.5°, 17.5°±0.5°, 19.0°±0.5°, 21.3°±0.5°, 23.8°±0.5°, 25.3°±0.5°, 25.8°±0.5° and 26.8°±0.5°.
7. A salt according to claim 1 which shows on X-ray diffraction peaks on the 2theta scale at 8.3°±0.5°, 8.8°±0.5°, 16.9°±0.5°, 17.5°±0.5°, 19.0°±0.5°, 21.3°±0.5°, 23.8°±0.5°, 25.3°±0.5°, 25.8°±0.5° and 26.8°±0.5°.
8. A salt according to claim 6 which also shows on X-ray diffraction at least 1 peak on the 2theta scale selected from the group consisting of 10.6°±0.520 , 13°±0.5°, 14.1°±0.5°, 17.5°±0.5°, 18.3°±0.5°, 20.7 °±0.5°, 22.3°±0.5°, 22.7°±0.5°, 23.1°0 ±0.5°, 28.2°±0.5°, 28.5°±0.5°, 29.1°±0.5°, 30.5°±0.5°, 31.3°±0.5°, 35.0°±0.5° and 36.8°±0.5°.
9. A salt according to claim 7 which also shows on X-ray diffraction peaks on the 2theta scale at 7.0°±0.5°0 , 9.2°±0.5°, 11.4°±0.5° and 27.5°±0.5°.
10. A pharmaceutical composition comprising a salt according to claim 1 .
11. A method of treating cancer comprising administration of a therapeutically effective amount of a salt according to claim 1 to a patient in need thereof,
wherein the cancer is selected from the group consisting of colon cancer, acute myeloid leukaemia and myelofibrosis.
12. A method according to claim 11 wherein the cancer is colon cancer.
13. A method according to claim 11 wherein the cancer is acute myeloid leukaemia.
14. A method according to claim 11 wherein the cancer is myelofibrosis.