Solid state forms of macrocyclic kinase inhibitors
Provided herein are salt forms of macrocyclic protein kinase inhibitors, pharmaceutical compositions containing the same, methods of making and using these compounds and compositions to treat proliferative disease mediated by kinase activity.
1. A crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12]heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting the x-ray powder diffraction pattern of FIG. 13 .
2. The crystalline citrate salt of claim 1 having a melting point of 191° C. as determined by differential scanning calorimetry.
3. A crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12]heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5°.
4. The crystalline citrate salt of claim 3 further characterized by a powder x-ray diffraction pattern reflection at 2 theta-15.0°.
5. The crystalline citrate salt of claim 3 or 4 further characterized by a powder x-ray diffraction pattern reflection at 2 theta-19.8°.
6. The crystalline citrate salt of claim 3 , 4 , or 5 further characterized by a melting point of 191° C. as determined by differential scanning calorimetry.
7. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting the x-ray powder diffraction pattern of FIG. 13 .
8. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting the x-ray powder diffraction pattern of FIG. 13 , wherein the pharmaceutical composition is substantially free of any other crystalline citrate salt.
9. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5°.
10. The pharmaceutical composition of claim 9 , wherein the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene is further characterized by a powder x-ray diffraction pattern reflection at 2 theta=15.0°.
11. The pharmaceutical composition of claim 9 or 10 , wherein the crystalline citrate salt of 14-methyl -20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene is further characterized by a powder x-ray diffraction pattern reflection at 2 theta=19.8°.
12. The pharmaceutical composition of claim 9 , 10 , or 11 , wherein the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene is further characterized by a melting point of 191° C. as determined by differential scanning calorimetry.
13. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5°, wherein the pharmaceutical composition is substantially free of any other crystalline citrate salt.
14. The pharmaceutical composition of claim 13 , wherein the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5° is further characterized by a reflection at 2 theta=15.0°.
15. The pharmaceutical composition of claim 13 or 14 , wherein the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12] heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5° is further characterized by a reflection at 2 theta=19.8°.
16. The pharmaceutical composition of claim 13 , 14 , or 15 , wherein the crystalline citrate salt of 14-methyl-20-oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12]heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene exhibiting a powder x-ray diffraction pattern reflection at 2 theta=21.5° is further characterized by a melting point of 191° C. as determined by differential scanning calorimetry.