Crystalline 5-(dimethylamino)-N-(4-(morpholinomethyl) phenyl)naphthalene-1-sulfonamide di-hydrochloride di-hydrate
Crystalline 5-(dimethylamino)-N-(4-(morpholinomethyl)phenyl)naphthalene-1-sulfonamide dihydrochloride dihydrate, methods of preparing the crystalline salt, pharmaceutical compositions containing the crystalline salt, and methods of treatment using the crystalline salt are disclosed.
1. A compound, crystalline 5-(dimethylamino)-N-(4-(morpholinomethyl)phenyl)naphthalene-1-sulfonamide:
wherein the compound is characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic diffraction peaks at least at 13.1°±0.2°, 14.6°±0.2°, 15.0°±0.2°, 18.1±0.2°, 22.2±0.2°, 22.6±0.2°, and 24.4±0.2° expressed as 2θ angles and determined using Cu-Kα radiation.
2. The compound of claim 1 , wherein the compound is characterized by an XRPD pattern comprising characteristic diffraction peaks at least at 13.1°±0.1°, 14.6°±0.1°, 15.0°±0.1°, 18.1±0.1°, 22.2±0.1°, 22.6±0.1°, and 24.4±0.1° expressed as 2θ angles and determined using Cu-Ka radiation.
3. The compound of claim 1 , wherein the compound is characterized by an XRPD pattern as shown in FIG. 5 .
4. The compound of claim 1 , wherein the compound has a primary melting onset temperature from 158° C. to 164° C., and wherein the primary melting onset temperature is determined by differential scanning calorimetry.
5. The compound of claim 1 , wherein the compound has a primary melting enthalpy from 60 J/g to 65 J/g, and wherein the primary melting enthalpy is determined by differential scanning calorimetry.
6. The compound of claim 1 , wherein the compound has a primary melting peak from 175 J/g to 182 J/g, and wherein the primary melting peak is determined by differential scanning calorimetry.
7. The compound of claim 1 , wherein the compound has a secondary melting onset temperature of 204.7° C., a secondary melting enthalpy of 20.7 J/g, and a secondary melting peak at 211.2° C.
8. The compound of claim 1 , wherein the compound exhibits a differential scanning calorimetry curve as shown in FIG. 6 .
9. A pharmaceutical composition comprising the compound of claim 1 .
10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound for treating a disease in a patient, wherein the disease is selected from cancer, an inflammatory disease, and an autoimmune disease.
11. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the pharmaceutical composition of claim 9 , wherein the disease is selected from breast cancer and melanoma.
12. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the pharmaceutical composition of claim 9 , wherein the disease is an inflammatory disease, wherein the inflammatory disease is selected from acute respiratory distress syndrome, focal segmental glomerulonephritis, atherosclerosis/acute coronary syndrome, chronic obstructive pulmonary disease, asthma, inflammatory bowel disease, Crohn's disease, psoriasis, lupus, multiple sclerosis, inflammation in hypercholesteremia, pain, diabetes, and rheumatoid arthritis.
13. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the pharmaceutical composition of claim 9 , wherein the disease is an autoimmune disease, wherein the autoimmune disease is selected from segmental glomerulonephritis, asthma, inflammatory disease, Crohn's disease, psoriasis, lupus, multiple sclerosis, pain, diabetes and rheumatoid arthritis.
14. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the pharmaceutical composition of claim 9 , wherein the disease is an age-related disease, wherein the age-related disease is selected from hearing loss, muscle degeneration, Werner's syndrome, cellular aging, and Alzheimer's disease.
15. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the pharmaceutical composition of claim 9 , wherein the disease is selected from acute lung injury, acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD).
16. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the compound of claim 1 , wherein the disease is selected from breast cancer and melanoma.
17. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the compound of claim 1 , wherein the disease is an inflammatory disease, wherein the inflammatory disease is selected from acute respiratory distress syndrome, focal segmental glomerulonephritis, atherosclerosis/acute coronary syndrome, chronic obstructive pulmonary disease, asthma, inflammatory bowel disease, Crohn's disease, psoriasis, lupus, multiple sclerosis, inflammation in hypercholesteremia, pain, diabetes, and rheumatoid arthritis.
18. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the compound of claim 1 , wherein the disease is an autoimmune disease, wherein the autoimmune disease is selected from segmental glomerulonephritis, asthma, inflammatory disease, Crohn's disease, psoriasis, lupus, multiple sclerosis, pain, diabetes and rheumatoid arthritis.
19. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the compound of claim 1 , wherein the disease is an age-related disease, wherein the age-related disease is selected from hearing loss, muscle degeneration, Werner's syndrome, cellular aging, and Alzheimer's disease.
20. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective of amount of the compound of claim 1 , wherein the disease is selected from acute lung injury, acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD).