(9E)-15-(2-pyrrolidin-1-yl-ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2.5).1(14,18)]hexacosa-1(24),2,4,9,14,16,18(26),20,22-nonaene citrate salt
View Patent ↗The present invention relates to certain salts of a 9E-15-(2-pyrrolidin-1-yl-ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14,16,18(26),20,22-nonaene (Compound I) which have been found to have improved properties. In particular the present invention relates to the citrate salt of this compound. The invention also relates to pharmaceutical compositions containing the citrate salt and methods of use of the citrate salt in the treatment of certain medical conditions.
1. A crystalline citrate salt of 9E-15-(2-pyrrolidin-1-yl-ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14,16,18(26),20,22-nonaene which shows on X-ray diffraction at least one peak on the 2theta scale selected from the group consisting of 10.0°±0.5°, 15.6°±0.5°, 17.2°±0.5° and 22.4°±0.5°.
2. The salt according to claim 1 wherein the salt is the 1:1 salt.
3. The salt according to claim 1 which shows on X-ray diffraction a peak on the 2theta scale at 22.4°±0.5°.
4. The salt according to claim 3 which also shows on X-ray diffraction peaks on the 2theta scale at 10.0°±0.5°, 15.6°±0.5° and 17.2°±0.5°.
5. The salt according to claim 1 which shows on X-ray diffraction at least four peaks on the 2theta scale selected from the group consisting of 7.9°±0.5°, 10.0°±0.5°, 15.6°±0.5°, 15.9°±0.5°, 16.8°±0.5°, 17.2°±0.5°, 21.1°±0.5°, and 22.4°±0.5°.
6. The 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 7.9°±0.5°, 10.0°±0.5°, 15.6°±0.5°, 15.9°±0.5°, 16.8°±0.5°, 17.2°±0.5°, 21.1°±0.5°, and 22.4°±0.5°.
7. The salt according to claim 1 which shows on X-ray diffraction peaks on the 2theta scale at 7.9°±0.5°, 10.0°±0.5°, 15.6°±0.5°, 15.9°±0.5°, 16.8°±0.5°, 17.2°±0.5°, 21.1°±0.5°, and 22.4°±0.5°.
8. The salt according to claim 7 which also shows on X-ray diffraction peaks on the 2theta scale at 11.1°±0.5°, 18.1°±0.5°, 21.8°±0.5°, 23.2°±0.5°, and 27.6°±0.5°.
9. The salt according to claim 8 which also shows on X-ray diffraction peaks on the 2theta scale at 7.0°±0.5°, 14.0°±0.5°, 19.0°±0.5°, 19.8°±0.5°, 23.6°±0.5°, 24.3°±0.5°, 25.2°±0.5°, 25.7°±0.5°, 26.1°±0.5°, 26.5°±0.5°, and 32.1°±0.5°.
10. A pharmaceutical composition comprising a salt according to claim 1 .
11. A method of treating a proliferative disorder selected from the group consisting of rheumatoid arthritis, acute myeloid leukemia and erythroleukemia comprising administration of a therapeutically effective amount of a salt according to claim 1 to a patient in need thereof.
12. The method according to claim 11 wherein the proliferative disorder is rheumatoid arthritis.
13. The method according to claim 11 wherein the proliferative disorder is acute myeloid leukemia.
14. The method according to claim 11 wherein the proliferative disorder is erythroleukemia.