HDAC inhibitor solid state forms
The present disclosure relates to the crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide and methods of making the same. The crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide is useful in preparation of pharmaceutical compositions and dosage forms for the treatment of cancer, immune disorders and inflammation.
1. A method of treating a condition in which HDAC has demonstrated a role in epigenetic regulation and pathology in an individual, the method comprising administering an effective amount of:
(a) valganciclovir; and
(b) Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide characterized by at least three X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3
thereby treating the condition in the individual.
2. The method of claim 1 , wherein the condition is inflammation, an immune disorder, or cancer.
3. The method of claim 2 , wherein the condition is cancer.
4. The method of claim 1 , wherein the amount of another crystalline form is 5% (w/w) or less.
5. The method of claim 1 , wherein the amount of an amorphous form is 5% (w/w) or less.
6. The method of claim 1 , wherein the amount of impurities is 3% or less.
7. A method of treating a condition in which HDAC has demonstrated a role in epigenetic regulation and pathology in an individual, the method comprising administering an effective amount of:
(a) valganciclovir; and
(b) Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide characterized by at least five X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3
thereby treating the condition in the individual.
8. The method of claim 7 , wherein the condition is inflammation, an immune disorder, or cancer.
9. The method of claim 8 , wherein the condition is cancer.
10. The method of claim 7 , wherein the amount of another crystalline form is 5% (w/w) or less.
11. The method of claim 7 , wherein the amount of an amorphous form is 5% (w/w) or 12 less.
12. The method of claim 7 , wherein the amount of impurities is 3% or less.
13. A method of treating a condition in which HDAC has demonstrated a role in epigenetic regulation and pathology in an individual, the method comprising administering an effective amount of:
(a) valganciclovir; and
(b) Crystalline mesylate Form 1 salt of N-hydroxy 2-{6-[(6-fluoro-quinolin-2-ylmethyl)-amino]-3-aza-bicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide, characterized by:
(i) at least two X-ray diffraction pattern reflections selected from a 2 theta value of 3.7°±0.3, 7.5°±0.3, 14.9°±0.3, 17.3°±0.3, 19.7°±0.3, 22.5°±0.3, 22.9°±0.3, or 30.1°±0.3; and
(ii) differential scanning calorimetry (DSC), wherein the DSC thermogram exhibits a single exothermic event with an onset temperature at about 222.1° C.±5.0 (433 J/g) or an exothermic peak at 225.8° C.±5.0;
thereby treating the condition in the individual.
14. The method of claim 13 , wherein the condition is inflammation, an immune disorder, or cancer.
15. The method of claim 14 , wherein the condition is cancer.
16. The method of claim 13 , wherein the amount of another crystalline form is 5% (w/w) or less.
17. The method of claim 13 , wherein the amount of an amorphous form is 5% (w/w) or less.
18. The method of claim 13 , wherein the amount of impurities is 3% or less.