WO/2007/055170 | NUCLEIC ACID BASE HAVING PERFLUOROALKYL GROUP AND METHOD FOR PRODUCING THE SAME |
WO/2001/073095 | PREPARATION OF DEOXYNUCLEOSIDES |
JPH0827151 | PRODUCTION OF PURINE |
LEWIS CHAD ARTHUR (US)
WO2021026803A1 | 2021-02-18 | |||
WO2021028854A1 | 2021-02-18 |
Claims: 1. A compound represented by Formula I: wherein X is maleic acid, benzenesulfonic acid, p-toluenesulfonic acid, 1,2- ethanedisulfonic acid, D-gluconic acid, gentisic acid, phosphoric acid, or L-aspartic acid. 2. The compound of claim 1, wherein the mole ratio of X to (S)-1-((R)-3-amino-1-(4-((6- amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3- yl)-2,2-difluoroethan-1-ol is about 1:1. 3. The compound of claim 1 or 2, wherein X is maleic acid. 4. The compound of claim 3, wherein the compound is in crystalline form. 5. The compound of claim 4, wherein the crystalline form further comprises water. 6. The compound of claim 5, wherein the mole ratio of water to (S)-1-((R)-3-amino-1-(4-((6- amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3- yl)-2,2-difluoroethan-1-ol is in the range of about 1:1 to about 3:1. 7. The compound of claim 6, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 8.3 ± 0.2, 11.1 ± 0.2, 16.9 ± 0.2, 18.2 ± 0.2, 19.3 ± 0.2, 24.5 ± 0.2, and 25.5 ± 0.2. 8. The compound of claim 7, wherein the X-ray powder diffraction pattern further comprises a peak at 7.4 ± 0.2. 9. The compound of claim 7 or 8, wherein the X-ray powder diffraction pattern further comprises a peak at 14.7 ± 0.2. 10. The compound of any one of claims 7-9, wherein the X-ray powder diffraction pattern further comprises a peak at 15.3 ± 0.2. 11. The compound of any one of claims 7-10, wherein the X-ray powder diffraction pattern further comprises a peak at 20.7 ± 0.2. 12. The compound of any one of claims 7-11, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 15%. 13. The compound of claim 6, characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 14. The compound of claim 6, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.1. 15. The compound of claim 1 or 2, wherein X is benzenesulfonic acid. 16. The compound of claim 15, wherein the compound is in crystalline form. 17. The compound of claim 16, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 8.6 ± 0.2, 12.6 ± 0.2, 14.4 ± 0.2, 17.3 ± 0.2, 17.7 ± 0.2, 20.0 ± 0.2, and 22.2 ± 0.2. 18. The compound of claim 17, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 20%. 19. The compound of claim 16 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 20. The compound of claim 16, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.2. 21. The compound of claim 1 or 2, wherein X is p-toluenesulfonic acid. 22. The compound of claim 21, wherein the compound is in crystalline form. 23. The compound of claim 22, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 5.1 ± 0.2, 6.3 ± 0.2, 7.9 ± 0.2, 13.7 ± 0.2, 15.9 ± 0.2, 19.4 ± 0.2, and 21.2 ± 0.2. 24. The compound of claim 23, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 5%. 25. The compound of claim 22, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.3. 26. The compound of claim 1 or 2, wherein X is 1,2-ethanedisulfonic acid. 27. The compound of claim 26, wherein the compound is in crystalline form. 28. The compound of claim 27, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.6 ± 0.2, 14.5 ± 0.2, 15.4 ± 0.2, 21.6 ± 0.2, and 24.6 ± 0.2. 29. The compound of claim 28, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 10%. 30. The compound of claim 27 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 31. The compound of claim 27, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.4. 32. The compound of claim 27, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 9.4 ± 0.2, 12.7 ± 0.2, 14.4 ± 0.2, 17.7 ± 0.2, 21.4 ± 0.2, 22.8 ± 0.2, and 24.5 ± 0.2. 33. The compound of claim 32, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 20%. 34. The compound of claim 27 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 35. The compound of claim 27, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.5. 36. The compound of claim 27, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 5.8 ± 0.2, 11.5 ± 0.2, and 16.6 ± 0.2. 37. The compound of claim 36, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 5%. 38. The compound of claim 27 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 39. The compound of claim 27, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.6. 40. The compound of claim 1 or 2, wherein X is D-gluconic acid. 41. The compound of claim 40, wherein the compound is in crystalline form. 42. The compound of claim 41, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.1 ± 0.2, 6.5 ± 0.2, 7.5 ± 0.2, 15.8 ± 0.2, 16.5 ± 0.2, 18.8 ± 0.2, and 24.8 ± 0.2. 43. The compound of claim 42, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 20%. 44. The compound of claim 41 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 45. The compound of claim 41, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.7. 46. The compound of claim 1 or 2, wherein X is gentisic acid. 47. The compound of claim 46, wherein the compound is in crystalline form. 48. The compound of claim 47, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 5.5 ± 0.2, 11.1 ± 0.2, 12.3 ± 0.2, 17.5 ± 0.2, and 19.9 ± 0.2. 49. The compound of claim 48, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 5%. 50. The compound of claim 47, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.8. 51. The compound of claim 1, wherein X is phosphoric acid. 52. The compound of claim 51, wherein the mole ratio of phosphoric acid to (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol is about 1:2. 53. The compound of claim 51 or 52, wherein the compound is in crystalline form. 54. The compound of claim 53, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.8 ± 0.2, 10.5 ± 0.2, 10.9 ± 0.2, 20.9 ± 0.2, and 21.1 ± 0.2. 55. The compound of claim 54, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 15%. 56. The compound of claim 53, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.9. 57. The compound of claim 53, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 7.1 ± 0.2, 8.2 ± 0.2, 10.8 ± 0.2, 14.7 ± 0.2, 16.3 ± 0.2, and 17.8 ± 0.2. 58. The compound of claim 57, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 5%. 59. The compound of claim 53, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.10. 60. The compound of claim 1 or 2, wherein X is L-aspartic acid. 61. The compound of claim 60, wherein the compound is in crystalline form. 62. The compound of claim 61, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.4 ± 0.2, 10.8 ± 0.2, 12.2 ± 0.2, 16.6 ± 0.2, 17.6 ± 0.2, 20.6 ± 0.2, 21.7 ± 0.2, and 25.6 ± 0.2. 63. The compound of claim 62, wherein the relative intensity of the peak at said diffraction angles (2θ) is at least 30%. 64. The compound of claim 61 characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . 65. The compound of claim 61, wherein the X-ray powder diffraction pattern is substantially as shown in FIG.11. 66. A pharmaceutical composition comprising a compound of any one of claims 1-65 and a pharmaceutically acceptable carrier. 67. A method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2), comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any one of claims 1-65 to treat the disease or condition. 68. The method of claim 67, wherein said disease or condition mediated by NSD2 is cancer. 69. The method of claim 67, wherein said disease or condition mediated by NSD2 is selected from solid tumors, leukemia, myeloma, lymphoma and hypertension. 70. The method of claim 67, wherein said disease or condition mediated by NSD2 is breast cancer, cervical cancer, skin cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia, non- Hodgkin’s lymphoma or pulmonary arterial hypertension. 71. The method of claim 67, wherein said disease or condition mediated by NSD2 is acute lymphoblastic leukaemia, skin squamous cell carcinoma or mantle cell lymphoma. 72. The method of any one of claims 67-71, wherein the subject is a human. 73. A method of inhibiting the activity of nuclear SET domain-containing protein 2 (NSD2), comprising contacting a NSD2 with an effective amount of a compound of any one of claims 1-65 to inhibit the activity of said NSD2. |
. [0156] In certain embodiments, the crystalline form is characterized as having an X-ray powder diffraction pattern substantially as shown in FIG.10. [0157] An X-ray powder diffraction pattern may be obtained using CuKα radiation. The temperature at which the X-ray powder diffraction pattern is obtained may be, for example, 25±2 degrees Celsius. [0158] In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry in the range of from about 55 degrees Celsius to about 70 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry at about 62 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry in the range of from about 95 degrees Celsius to about 110 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry at about 100 degrees Celsius. [0159] In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry in the range of from about 230 degrees Celsius to about 245 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry at about 237 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry in the range of from about 245 degrees Celsius to about 260 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry at about 254 degrees Celsius. [0160] The description above describes multiple embodiments relating to phosphoric acid salts of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan -1-ol. The patent application specifically contemplates all combinations of the embodiments. H. L-Aspartic Acid Salt of (S)-1-((R)-3-Amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6- (2,5-difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2 ,2-difluoroethan-1-ol [0161] In certain embodiments, the compound is an L-aspartic acid salt of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl) pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. In certain embodiments, the mole ratio of L-aspartic acid to (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan -1-ol is about 2:3. In certain embodiments, the mole ratio of L-aspartic acid to (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin- 9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridin-3-yl)pi peridin-3-yl)-2,2-difluoroethan- 1-ol is 2:3. [0162] In certain embodiments, the compound is in crystalline form. [0163] In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.4 ± 0.2, 10.8 ± 0.2, 12.2 ± 0.2, 16.6 ± 0.2, 17.6 ± 0.2, 20.6 ± 0.2, 21.8 ± 0.2, and 25.6 ± 0.2. In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern further comprising a peak at the following diffraction angle (2θ): 22.9 ± 0.2. In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern further comprising a peak at the following diffraction angle (2θ): 23.3 ± 0.2. In certain embodiments, the crystalline form exhibits an X- ray powder diffraction pattern further comprising a peak at the following diffraction angle (2θ): 23.8 ± 0.2. In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern further comprising a peak at the following diffraction angle (2θ): 27.0 ± 0.2. In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern further comprising a peak at the following diffraction angle (2θ): 28.3 ± 0.2. In certain embodiments, the crystalline form exhibits an X-ray powder diffraction pattern further comprising peaks at the following diffraction angles (2θ): 22.9 ± 0.2, 23.3 ± 0.2, 23.8 ± 0.2, 27.0 ± 0.2, and 28.3 ± 0.2. [0164] In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 5%. In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 10%. In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 15%. In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 20%. In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 25%. In certain embodiments, the relative intensity of the peak at said diffraction angles (2θ) is at least 30%. [0165] In certain embodiments, the crystalline form is characterized by the following X-ray powder diffraction pattern expressed in terms of diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): . [0166] In certain embodiments, the crystalline form is characterized as having an X-ray powder diffraction pattern substantially as shown in FIG.11. [0167] An X-ray powder diffraction pattern may be obtained using CuKα radiation. The temperature at which the X-ray powder diffraction pattern is obtained may be, for example, 25±2 degrees Celsius. [0168] In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry in the range of from about 225 degrees Celsius to about 240 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with an onset as determined by differential scanning calorimetry at about 232 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry in the range of from about 245 degrees Celsius to about 260 degrees Celsius. In certain embodiments, the crystalline form has an endotherm with a peak as determined by differential scanning calorimetry at about 254 degrees Celsius. [0169] The description above describes multiple embodiments relating to an L-aspartic acid salt of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan -1-ol. The patent application specifically contemplates all combinations of the embodiments. II. Therapeutic Applications of Salts of (S)-1-((R)-3-Amino-1-(4-((6-amino-9H-purin- 9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridin-3-yl)pi peridin-3-yl)-2,2- difluoroethan-1-ol [0170] Compounds described herein, such as a compound of Formula I, or other compounds in Section I, provide therapeutic benefits to subjects suffering from cancer and other disorders. Accordingly, one aspect of the invention provides a method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2). The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound described herein, such as a compound of Formula I, or other compounds in Section I, to treat the disease or condition. In certain embodiments, the particular compound is a compound defined by one of the embodiments described above. [0171] Examples of diseases or conditions that are mediated by NSD2 include but is not limited to breast cancer, cervical cancer, skin cancer (particularly skin squamous cell carcinoma), ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia (particularly acute lymphoblastic leukemia), non- Hodgkin’s lymphoma (particularly mantle cell lymphoma), and pulmonary arterial hypertension. [0172] In certain embodiments, said disease or condition mediated by NSD2 is cancer. [0173] In certain embodiments, said disease or condition mediated by NSD2 is selected from a solid tumor, leukemia, myeloma, lymphoma, and hypertension. In certain embodiments, said disease or condition mediated by NSD2 is a solid tumor. In certain embodiments, said disease or condition mediated by NSD2 is selected from leukemia, myeloma, and lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is leukemia. In certain embodiments, said disease or condition mediated by NSD2 is myeloma. In certain embodiments, said disease or condition mediated by NSD2 is lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is hypertension. [0174] In certain embodiments, said disease or condition mediated by NSD2 is breast cancer, cervical cancer, skin cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia, non-Hodgkin’s lymphoma, or pulmonary arterial hypertension. In certain embodiments, said disease or condition mediated by NSD2 is breast cancer. In certain embodiments, said disease or condition mediated by NSD2 is cervical cancer. In certain embodiments, said disease or condition mediated by NSD2 is ovarian cancer. In certain embodiments, said disease or condition mediated by NSD2 is gastric cancer. In certain embodiments, said disease or condition mediated by NSD2 is prostate cancer. In certain embodiments, said disease or condition mediated by NSD2 is pancreatic cancer. In certain embodiments, said disease or condition mediated by NSD2 is hepatocellular carcinoma. In certain embodiments, said disease or condition mediated by NSD2 is head and neck cancer. In certain embodiments, said disease or condition mediated by NSD2 is a peripheral nerve sheath tumor. In certain embodiments, said disease or condition mediated by NSD2 is osteosarcoma. In certain embodiments, said disease or condition mediated by NSD2 is multiple myeloma. In certain embodiments, said disease or condition mediated by NSD2 is neuroblastoma. In certain embodiments, said disease or condition mediated by NSD2 is pulmonary arterial hypertension. [0175] In certain embodiments, said disease or condition mediated by NSD2 is acute lymphoblastic leukaemia, skin squamous cell carcinoma, or mantle cell lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is acute lymphoblastic leukaemia. In certain embodiments, said disease or condition mediated by NSD2 is skin squamous cell carcinoma. In certain embodiments, said disease or condition mediated by NSD2 is mantle cell lymphoma. [0176] In certain embodiments, said disease or condition mediated by NSD2 is lung cancer. In certain embodiments, said disease or condition mediated by NSD2 is small cell or non-small cell lung cancer. In certain embodiments, said disease or condition mediated by NSD2 is small cell lung cancer. In certain embodiments, said disease or condition mediated by NSD2 is non- small cell lung cancer. [0177] In certain embodiments, said disease or condition mediated by NSD2 is leukemia. In certain embodiments, said disease or condition mediated by NSD2 is acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or chronic myelomonocytic leukemia (CMML). In certain embodiments, said disease or condition mediated by NSD2 is AML. In certain embodiments, said disease or condition mediated by NSD2 is CML. In certain embodiments, said disease or condition mediated by NSD2 is CMML. [0178] In certain embodiments, said disease or condition mediated by NSD2 is skin cancer. In certain embodiments, said disease or condition mediated by NSD2 is melanoma, basal cell carcinoma, or squamous cell carcinoma. In certain embodiments, said disease or condition mediated by NSD2 is melanoma. In certain embodiments, said disease or condition mediated by NSD2 is basal cell carcinoma. [0179] In certain embodiments, said disease or condition mediated by NSD2 is lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is Hodgkin’s lymphoma or non-Hodgkin’s lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is Hodgkin’s lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is non-Hodgkin’s lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is mantle cell lymphoma or diffuse large B cell lymphoma. In certain embodiments, said disease or condition mediated by NSD2 is diffuse large B cell lymphoma. [0180] In certain embodiments, said disease or condition mediated by NSD2 is myeloma. [0181] In certain embodiments, said disease or condition mediated by NSD2 is thyroid cancer. In certain embodiments, said disease or condition mediated by NSD2 is colon cancer. [0182] In certain embodiments, the cancer overexpresses NSD2. In certain embodiments, the cancer has a mutation in NSD2. In certain embodiments, the cancer has an activating mutation in NSD2. In certain embodiments, the cancer has the t(4;14)(p16.3;q32.3) translocation in NSD2. In certain embodiments, the cancer has an E1099K mutation in NSD2. In certain embodiments, the cancer has an T1150A mutation in NSD2. [0183] In certain embodiments, the subject is a human. In certain embodiments, the subject is an adult human. In certain embodiments, the subject is a pediatric human. In certain embodiments, the subject is a geriatric human. [0184] Another aspect of the invention provides for the use of a compound described herein (such as a compound of Formula I, or other compounds in Section I) in the manufacture of a medicament. In certain embodiments, the medicament is for treating a disease or condition described herein, such as cancer. [0185] Another aspect of the invention provides for the use of a compound described herein (such as a compound of Formula I, or other compounds in Section I) for treating a disease or condition, such as a disease or condition described herein (for example, cancer). [0186] Further, compounds described herein, such as a compound of Formula I, or other compounds in Section I, inhibit the activity of nuclear SET domain-containing protein 2 (NSD2). Accordingly, another aspect of the invention provides a method of inhibiting the activity of nuclear SET domain-containing protein 2 (NSD2). The method comprises contacting a NSD2 with an effective amount of a compound described herein, such as a compound of Formula I, or other compounds in Section I, to inhibit the activity of said NSD2. In certain embodiments, the particular compound is a compound defined by one of the embodiments described above. III. Combination Therapy [0187] Another aspect of the invention provides for combination therapy. Compounds described herein (e.g., a compound of Formula I, or other compounds in Section I) may be used in combination with additional therapeutic agents to treat a disease or condition, such as a cancer. [0188] Accordingly, in some embodiments, the present invention provides a method of treating a disclosed disease or condition comprising administering to a patient in need thereof an effective amount of a compound disclosed herein and co-administering simultaneously or sequentially an effective amount of one or more additional therapeutic agents, such as those described herein. In some embodiments, the method includes co-administering one additional therapeutic agent. In some embodiments, the method includes co-administering two additional therapeutic agents. [0189] One or more other therapeutic agents may be administered separately from a compound or composition of the invention, as part of a multiple dosage regimen. Alternatively, one or more other therapeutic agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as a multiple dosage regime, one or more other therapeutic agent and a compound or composition of the invention may be administered simultaneously, sequentially or within a period of time from one another. [0190] In certain embodiments, the additional therapeutic agent is an anti-cancer agent, anti- allergic agent, anti-nausea agent (or anti-emetic), pain reliever, cytoprotective agent, or a combination thereof. In certain embodiments, the additional therapeutic agent is an anti-cancer agent, an analgesic, an anti-inflammatory agent, or a combination thereof. [0191] In certain embodiments, the additional therapeutic agent is an anti-cancer agent or chemo-therapeutic agent. Examples of anti-cancer agents considered for use in combination therapies of the invention include but are not limited erlotinib, bortezomib, fulvestrant, sunitib, imatinib mesylate, letrozole, finasunate, platins such as oxaliplatin, carboplatin, and cisplatin, finasunate, fluorouracil, rapamycin, leucovorin, lapatinib, lonafamib, sorafenib, gefitinib, camptothecin, topotecan, bryostatin, adezelesin, anthracyclin, carzelesin, bizelesin, dolastatin, auristatins, duocarmycin, eleutherobin, taxols such as paclitaxel or docetaxel, cyclophosphamide, doxorubicin, vincristine, prednisone or prednisolone, other alkylating agents such as mechlorethamine, chlorambucil, and ifosfamide, antimetabolites such as azathioprine or mercaptopurine, other microtubule inhibitors (vinca alkaloids like vincristine, vinblastine, vinorelbine, and vindesine, as well as taxanes), podophyllotoxins (etoposide, teniposide, etoposide phosphate, and epipodophyllotoxins), topoisomerase inhibitors, other cytotoxins such as actinomycin, daunorubicin, valrubicin, idarubicin, edrecolomab, epirubicin, bleomycin, plicamycin, mitomycin, as well as other anticancer antibodies (cetuximab, bevacizumab, ibritumomab, abagovomab, adecatumumab, afutuzumab, alacizumab, alemtuzumab, anatumomab, apolizumab, bavituximab, belimumab, bivatuzumab mertansine, blinatumomab, brentuximab vedotin, cantuzumab mertansine, catumazomab, cetuximab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, conatumumab, dacetuzumab, daclizumab, detumomab, ecromeximab, edrecolomab, elotuzumab, epratuzumab, ertumaxomab, etaracizumab, farletuzumab, figitumumab, fresolimumab, galiximab, gembatumumab vedotin, gemtuzumab, ibritumomab tiuxetan, inotuzumab ozogamicin, intetumumab, ipilimumab, iratumumab, labetuzumab, lexatumumab, lintuzumab, lucatumumab, lumilisimab, mapatumumab, matuzumab, milatuzumab, mitumomab, nacolomab tafenatox, naptumomab estafenatox, necitumumab, nimotuzumab, ofatumumab, olaratumab, oportuzumab monatox, oregovomab, panitumumab, pemtumomab, pertuzumab, pintumomab, pritumumab, ramucirumab, rilotumumab, robatumumab, rituximab, sibrotuzumab, tacatuzumab tetraxetan, taplitumomab paptox, tenatumomab, ticilimumab, tigatuzumab, tositumomab or 131 I-tositumomab, trastuzumab, tremelimumab, tuocotuzumab celmoleukin, veltuzumab, visilizumab, volocixumab, votumumab, zalutumumab, zanolimumab, IGN-101, MDX-010, ABX-EGR, EMD72000, ior-t1, MDX-220, MRA, H-11 scFv, huJ591, TriGem, TriAb, R3, MT-201, G-250, ACA-125, Onyvax-105, CD:-960,Cea-Vac, BrevaRex AR54, IMC-1C11, GlioMab-H, ING-1, anti-LCG MAbs, MT-103, KSB-303, Therex, KW2871, anti-HMI.24, Anti-PTHrP, 2C4 antibody, SGN-30, TRAIL-RI MAb, Prostate Cancer antibody, H 2 2xKi-r, ABX-Mai, Imuteran, Monopharm-C), and antibody-drug conjugates comprising any of the above agents (especially auristatins MMAE and MMAF, maytansinoids like DM-1, calicheamycins, or various cytotoxins). [0192] In certain embodiments, the additional therapeutic agent is selected from anastrozole (ARIMIDEX®), bicalutamide (CASODEX®), bleomycin sulfate (BLENOXANE®), busulfan (MYLERAN®), busulfan injection (BUSULFEX®), capecitabine (XELODA®), N4- pentoxycarbonyl-5-deoxy-5-fluorocytidine, carboplatin (PARAPLATIN®), carmustine (BiCNU®), chlorambucil (LEUKERAN®), cisplatin (PLATINOL®), cladribine (LEUSTATIN®), cyclophosphamide (CYTOXAN® or NEOSAR®), cytarabine, cytosine arabinoside (CYTOSAR-U®), cytarabine liposome injection (DEPOCYT®), dacarbazine (DTIC-Dome®), dactinomycin (actinomycin D, COSMEGAN®), daunorubicin hydrochloride (CERUBIDINE®), daunorubicin citrate liposome injection (DAUNOXOME®), dexamethasone, docetaxel (TAXOTERE®), doxorubicin hydrochloride (ADRIAMYCIN®, RUBEX®), etoposide (VEPESID®), fludarabine phosphate (FLUDARA®), 5-fluorouracil (ADRUCIL®, EFUDEX®), flutamide (EULEXIN®), tezacitibine, gemcitabine (difluorodeoxycitidine), hydroxyurea (HYDREA®), idarubicin (IDAMYCIN®), ifosfamide (IFEX®), irinotecan (CAMPTOSAR®), L-asparaginase (ELSPAR®), leucovorin calcium, melphalan (ALKERAN®), 6-mercaptopurine (PURINETHOL®), methotrexate (FOLEX®), mitoxantrone (NOVANTRONE®), gemtuzumab ozogamicin (MYLOTARGTM), paclitaxel (TAXOL®), nab-paclitaxel (ABRAXANE®), phoenix (Yttrium90/MX-DTPA), pentostatin, polifeprosan 20 with carmustine implant (GLIADEL®), tamoxifen citrate (NOLVADEX®), teniposide (VUMON®), 6-thioguanine, thiotepa, tirapazamine (TIRAZONE®), topotecan hydrochloride for injection (HYCAMPTIN®), vinblastine (VELBAN®), vincristine (ONCOVIN®), and vinorelbine (NAVELBINE®). [0193] In certain embodiments, the additional therapeutic agent is capable of inhibiting BRAF, MEK, CDK4/6, SHP-2, HDAC, EGFR, MET, mTOR, PI3K or AKT, or a combination thereof. In a particular embodiment, the compounds of the present invention are combined with another therapeutic agent selected from vemurafinib, debrafinib, LGX818, trametinib, MEK162, LEE011, PD-0332991, panobinostat, verinostat, romidepsin, cetuximab, gefitinib, erlotinib, lapatinib, panitumumab, vandetanib, INC280, everolimus, simolimus, BMK120, BYL719 or CLR457, or a combination thereof. [0194] In certain embodiments, the additional therapeutic agent is selected based on the disease or condition that is being treated. For example, in the treatment of melanoma, the additional therapeutic agent is selected from aldesleukin (e.g., PROLEUKIN®), dabrafenib (e.g., TAFINLAR®), dacarbazine, recombinant interferon alfa-2b (e.g., INTRON® A), ipilimumab, trametinib (e.g., MEKINIST®), peginterferon alfa-2b (e.g., PEGINTRON®, SYLATRONTM), vemurafenib (e.g., ZELBORAF®)), and ipilimumab (e.g., YERVOY®). [0195] For the treatment of ovarian cancer, the additional therapeutic agent is selected from doxorubicin hydrochloride (Adriamycin®), carboplatin (PARAPLATIN®), cyclophosphamide (CYTOXAN®, NEOSAR®), cisplatin (PLATINOL®, PLATINOL-AQ®), doxorubicin hydrochloride liposome (DOXIL®, DOX-SL®, EVACET®, LIPODOX®), gemcitabine hydrochloride (GEMZAR®), topotecan hydrochloride (HYCAMTIN®), and paclitaxel (TAXOL®). [0196] For the treatment of thyroid cancer, the additional therapeutic agent is selected from doxorubicin hydrochloride (Adriamycin®), cabozantinib-S-malate (COMETRIQ®), and vandetanib (CAPRELSA®). [0197] For the treatment of colon cancer, the additional therapeutic agent is selected from fluorouracil (e.g., ADRUCIL®, EFUDEX®, FLUOROPLEX®), bevacizumab (AVASTIN®), irinotecan hydrochloride (CAMPTOSTAR®), capecitabine (XELODA®), cetuximab (ERBITUX®), oxaliplatin (ELOXATIN®), leucovorin calcium (WELLCOVORIN®), regorafenib (STIVARGA®), panitumumab (VECTIBIX®), and ziv-aflibercept (ZALTRAP®). [0198] For the treatment of lung cancer, the additional therapeutic agent is selected from methotrexate, methotrexate LPF (e.g., FOLEX®, FOLEX PFS®, Abitrexate®, MEXATE®, MEXATE-AQ®), paclitaxel (TAXOL®), paclitaxel albumin-stabilized nanoparticle formulation (ABRAXANE®), afatinib dimaleate (GILOTRIF®), pemetrexed disodium (ALIMTA®), bevacizumab (AVASTIN®), carboplatin (PARAPLATIN®), cisplatin (PLATINOL®, PLATINOL-AQ®), crizotinib (XALKORI®), erlotinib hydrochloride (TARCEVA®), gefitinib (IRESSA®), and gemcitabine hydrochloride (GEMZAR®). [0199] For the treatment of pancreatic cancer, the other therapeutic agent may be selected from fluorouracil (ADRUCIL®), EFUDEX®, FLUOROPLEX®), erlotinib hydrochloride (TARCEVA®), gemcitabine hydrochloride (GEMZAR®), and mitomycin or mitomycin C (MITOZYTREXTM, MUTAMYCIN®). [0200] For the treatment of cervical cancer, the additional therapeutic agent is selected from bleomycin (BLENOXANE®), cisplatin (PLATINOL®, PLATINOL-AQ®) and topotecan hydrochloride (HYCAMTIN®). [0201] For the treatment of head and neck cancer, the additional therapeutic agent is selected from methotrexate, methotrexate LPF (e.g., FOLEX®, FOLEX PFS®, Abitrexate®, MEXATE®, MEXATE-AQ®), fluorouracil (ADRUCIL®, EFUDEX®, FLUOROPLEX®), bleomycin (BLENOXANE®), cetuximab (ERBITUX®), cisplatin (PLATINOL®, PLATINOL-AQ®) and docetaxel (TAXOTERE®). [0202] For the treatment of leukemia, including chronic myelomonocytic leukemia (CMML), the additional therapeutic agent is selected from bosutinib (BOSULIF®), cyclophosphamide (CYTOXAN®, NEOSAR®), cytarabine (CYTOSAR-U®, TARABINE PFS®), dasatinib (SPRYCEL®), imatinib mesylate (GLEEVEC®), ponatinib (ICLUSIG®), nilotinib (TASIGNA®) and omacetaxine mepesuccinate (SYNRIBO®). [0203] In some instances, patients may experience allergic reactions to the compounds of the present invention and/or other anti-cancer agent(s) during or after administration. Therefore, anti-allergic agents may be administered to minimize the risk of an allergic reaction. Suitable anti-allergic agents include corticosteroids, such as dexamethasone (e.g., DECADRON®), beclomethasone (e.g., BECLOVENT®), hydrocortisone (also known as cortisone, hydrocortisone sodium succinate, hydrocortisone sodium phosphate; e.g., ALA- CORT®, hydrocortisone phosphate, Solu-CORTEF®, HYDROCORT Acetate® and LANACORT®), prednisolone (e.g., DELTA-Cortel®, ORAPRED®, PEDIAPRED® and PRELONE®), prednisone (e.g., DELTASONE®, LIQUID RED®, METICORTEN® and ORASONE®), methylprednisolone (also known as 6-methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate; e.g., DURALONE®, MEDRALONE®, MEDROL®, M-PREDNISOL® and SOLU-MEDROL®); antihistamines, such as diphenhydramine (e.g., BENADRYL®), hydroxyzine, and cyproheptadine; and bronchodilators, such as the beta-adrenergic receptor agonists, albuterol (e.g., PROVENTIL®), and terbutaline (BRETHINE®). [0204] In other instances, patients may experience nausea during and after administration of the compound of the present invention and/or other anti-cancer agent(s). Therefore, anti- emetics may be administered in preventing nausea (upper stomach) and vomiting. Suitable anti-emetics include aprepitant (EMEND®), ondansetron (ZOFRAN®), granisetron HCl (KYTRIL®), lorazepam (ATIVAN®. dexamethasone (DECADRON®), prochlorperazine (COMPAZINE®), casopitant (REZONIC® and Zunrisa®), and combinations thereof. [0205] In yet other instances, medication to alleviate the pain experienced during the treatment period is prescribed to make the patient more comfortable. Common over-the- counter analgesics, such TYLENOL®, are often used. Opioid analgesic drugs such as hydrocodone/paracetamol or hydrocodone/acetaminophen (e.g., VICODIN®), morphine (e.g., ASTRAMORPH® or AVINZA®), oxycodone (e.g., OXYCONTIN® or PERCOCET®), oxymorphone hydrochloride (OPANA®), and fentanyl (e.g., DURAGESIC®) are also useful for moderate or severe pain. [0206] Furthermore, cytoprotective agents (such as neuroprotectants, free-radical scavengers, cardioprotectors, anthracycline extravasation neutralizers, nutrients and the like) may be used as an adjunct therapy to protect normal cells from treatment toxicity and to limit organ toxicities. Suitable cytoprotective agents include amifostine (ETHYOL®), glutamine, dimesna (TAVOCEPT®), mesna (MESNEX®), dexrazoxane (ZINECARD® or TOTECT®), xaliproden (XAPRILA®), and leucovorin (also known as calcium leucovorin, citrovorum factor and folinic acid). [0207] In yet another aspect, a compound of the present invention may be used in combination with known therapeutic processes, for example, with the administration of hormones or in radiation therapy. In certain instances, a compound of the present invention may be used as a radiosensitizer, especially for the treatment of tumors which exhibit poor sensitivity to radiotherapy. [0208] The doses and dosage regimen of the active ingredients used in the combination therapy may be determined by an attending clinician. In certain embodiments, the compound described herein (e.g., a compound of Formula I, or other compounds in Section I) and the additional therapeutic agent(s) are administered in doses commonly employed when such agents are used as monotherapy for treating the disease or condition. In other embodiments, the compound described herein (e.g., a compound of Formula I, or other compounds in Section I) and the additional therapeutic agent(s) are administered in doses lower than the doses commonly employed when such agents are used as monotherapy for treating the disease or condition. In certain embodiments, the compound described herein (e.g., a compound of Formula I, or other compounds in Section I) and the additional therapeutic agent(s) are present in the same composition, which is suitable for oral administration. [0209] In certain embodiments, the compound described herein (e.g., a compound of Formula I, or other compounds in Section I) and the additional therapeutic agent(s) may act additively or synergistically. A synergistic combination may allow the use of lower dosages of one or more agents and/or less frequent administration of one or more agents of a combination therapy. A lower dosage or less frequent administration of one or more agents may lower toxicity of the therapy without reducing the efficacy of the therapy. [0210] Another aspect of this invention is a kit comprising a therapeutically effective amount of a compound described herein (e.g., a compound of Formula I, or other compounds in Section I), a pharmaceutically acceptable carrier, vehicle or diluent, and optionally at least one additional therapeutic agent listed above. In certain embodiments, the kit further comprises instructions, such as instructions for treating a disease described herein. IV. Pharmaceutical Compositions and Dosing Considerations [0211] As indicated above, the invention provides pharmaceutical compositions, which comprise a therapeutically-effective amount of one or more of the compounds described above, formulated together with one or more pharmaceutically acceptable carriers (additives) and/or diluents. The pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for the following: (1) oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; (2) parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; (3) topical application, for example, as a cream, ointment, or a controlled-release patch or spray applied to the skin; (4) intravaginally or intrarectally, for example, as a pessary, cream or foam; (5) sublingually; (6) ocularly; (7) transdermally; or (8) nasally. In certain embodiments, the invention provides a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula I, or other compounds in Section I) and a pharmaceutically acceptable carrier. [0212] The phrase “therapeutically effective amount” as used herein means that amount of a compound, material, or composition comprising a compound of the present invention which is effective for producing some desired therapeutic effect in at least a sub-population of cells in an animal at a reasonable benefit/risk ratio applicable to any medical treatment. [0213] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0214] Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions. [0215] Examples of pharmaceutically-acceptable antioxidants include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. [0216] Formulations of the present invention include those suitable for oral, nasal, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, out of one hundred percent, this amount will range from about 0.1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, most preferably from about 10 percent to about 30 percent. [0217] In certain embodiments, a formulation of the present invention comprises an excipient selected from the group consisting of cyclodextrins, celluloses, liposomes, micelle forming agents, e.g., bile acids, and polymeric carriers, e.g., polyesters and polyanhydrides; and a compound of the present invention. In certain embodiments, an aforementioned formulation renders orally bioavailable a compound of the present invention. [0218] Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. [0219] Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present invention as an active ingredient. A compound of the present invention may also be administered as a bolus, electuary or paste. [0220] In solid dosage forms of the invention for oral administration (capsules, tablets, pills, dragees, powders, granules, trouches and the like), the active ingredient is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds and surfactants, such as poloxamer and sodium lauryl sulfate; (7) wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non-ionic surfactants; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, zinc stearate, sodium stearate, stearic acid, and mixtures thereof; (10) coloring agents; and (11) controlled release agents such as crospovidone or ethyl cellulose. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-shelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. [0221] A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface- active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. [0222] The tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be formulated for rapid release, e.g., freeze-dried. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. [0223] Liquid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. [0224] Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. [0225] Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. [0226] Formulations of the pharmaceutical compositions of the invention for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound. [0227] Formulations of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate. [0228] Dosage forms for the topical or transdermal administration of a compound of this invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically-acceptable carrier, and with any preservatives, buffers, or propellants which may be required. [0229] The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. [0230] Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. [0231] Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel. [0232] Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention. [0233] Pharmaceutical compositions of this invention suitable for parenteral administration comprise one or more compounds of the invention in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain sugars, alcohols, antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents. [0234] Examples of suitable aqueous and nonaqueous carriers which may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. [0235] These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms upon the subject compounds may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin. [0236] In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. [0237] Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissue. [0238] When the compounds of the present invention are administered as pharmaceuticals, to humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99% (more preferably, 10 to 30%) of active ingredient in combination with a pharmaceutically acceptable carrier. [0239] The preparations of the present invention may be given orally, parenterally, topically, or rectally. They are of course given in forms suitable for each administration route. For example, they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administrations are preferred. [0240] The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. [0241] The phrases “systemic administration,” “administered systemically,” “peripheral administration” and “administered peripherally” as used herein mean the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient’s system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration. [0242] These compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. [0243] Regardless of the route of administration selected, the compounds of the present invention, which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically-acceptable dosage forms by conventional methods known to those of skill in the art. [0244] Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. [0245] The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the rate and extent of absorption, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. [0246] A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. [0247] In general, a suitable daily dose of a compound of the invention will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Preferably, the compounds are administered at about 0.01 mg/kg to about 200 mg/kg, more preferably at about 0.1 mg/kg to about 100 mg/kg, even more preferably at about 0.5 mg/kg to about 50 mg/kg. When the compounds described herein are co-administered with another agent (e.g., as sensitizing agents), the effective amount may be less than when the agent is used alone. [0248] If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. Preferred dosing is one administration per day. [0249] The invention further provides a unit dosage form (such as a tablet or capsule) comprising a compound described herein in a therapeutically effective amount for the treatment of a disease or condition described herein. EXAMPLES [0250] The invention now being generally described, will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention. Starting materials described herein can be obtained from commercial sources or may be readily prepared from commercially available materials using transformations known to those of skill in the art. Analytical Techniques [0251] X-ray powder diffraction was performed using either a Rigaku MiniFlex 600 or a Bruker D8 Advance equipped with LYNXEYE detector. Both instruments were operated in reflection mode (i.e., Bragg-Brentano geometry). Samples were prepared on Si zero-return wafers. Parameters for XRPD using the Rigaku MiniFlex 600 were: [0252] Parameters for XRPD using the Bruker D8 Advance were: [0253] Simultaneous thermogravimetric analysis and differential scanning calorimetry was performed using a Mettler Toledo TGA/DSC 3+ . Protective and purge gas was nitrogen at a flow rate of 20-30 mL/min and 50-100 mL/min, respectively. The sample (5-10 mg) was weighed directly into a hermetic aluminum pan with a pinhole and analyzed according to the following parameters: ramp method, heating rate 10.0 °C/min, and temperature range 30 to 300 °C. [0254] Differential scanning calorimetry was performed using a Mettler Toledo DSC 3+ (with method gas flow of 60.00 mL/min) or a TA Discovery DSC (with method gas flow of 50.00 mL/min). With either instrument, the sample (1-5 mg) was weighed directly into a 40 µL hermetic aluminum pan with a pinhole and analyzed according to the following parameters: ramp method, heating rate 10.0 °C/min, temperature range 30 to 300 °C, and method gas N 2 . [0255] Dynamic vapor sorption was performed using a Q5000SA. The sample (5-15 mg) was loaded into a metallic quartz sample pan, suspended from a microbalance, and exposed to a humidified stream of nitrogen gas. Weight changes were relative to a matching empty reference pan opposite the sample, suspended from the microbalance. The sample was held for a minimum of 10 min at each humidity level and only progressed to the next humidity level if there was < 0.002 % change in weight between measurements (interval: 5 s) or 45 min had elapsed (for 5-65% RH) or 2 hours had elapsed (for 80 and 95% RH). The following program was used: 1. Equilibration at 50 % RH 2. 50 % to 5 % (50 %, 35 %, 20 %, and 5 %) 3. 5 % to 95 % (5 %, 20 %, 35 %, 50 %, 65 %, 80 %, and 95 %) 4. 95 % to 5 % (95 %, 80 %, 65 %, 50 %, 35 %, 20 %, and 5 %) 5. 5 % to 50 % (5 %, 20 %, 35 %, and 50 %). [0256] Karl Fischer (KF) titration for water determination was performed using a Mettler Toledo C20S Coulometric KF Titrator equipped with a current generator cell with a diaphragm, and a double-platinum-pin electrode. The range of detection of the instrument is 1 ppm to 5 % water. Aquastar TM CombiCoulomat fritless reagent was used in both the anode and cathode compartments. Samples of approximately 0.03-0.10 g were dissolved in the anode compartment and titrated until the solution potential dropped below 100 mV. Hydranal 1 wt % water standard was used for validation prior to sample analysis. [0257] Proton nuclear magnetic resonance ( 1 H NMR) spectroscopy was performed on a Bruker Avance 500 MHz spectrometer. Solids were dissolved in 0.60-0.75 mL of deuterated solvent in a 4 mL vial, transferred to an NMR tube (Wilmad 5 mm thin wall 8" 200 MHz, 506- PP-8) and analyzed according to the following parameters: EXAMPLE 1 -- Preparation of Maleic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6-amino-9H- purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridin-3 -yl)piperidin-3-yl)-2,2- difluoroethan-1-ol [0258] (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan -1-ol (516 mg) was charged to a vial followed by maleic acid (122 mg) and 2-propanol:water (20 volumes, 9:1, v:v). The mixture was heated to 45°C with stirring for 2 hours (the solids dissolved quickly upon heating, then precipitated within about 15 minutes to form a thick, white slury), and then the mixture was allowed to cool to room temperature with stirring overnight. Solids in the resulting mixture were collected by filtration, washed with 2-propanol:water (9:1, v/v), and dried overnight in a vacuum-oven at 50°C to provide the title compound (441 mg, ~70 % yield) as a crystalline solid. [0259] An X-ray powder diffractogram of the crystalline solid is provided in FIG.1. Tabulated characteristics of the X-ray powder diffractogram in FIG.1 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-R AY P OWDER D IFFRACTOGRAM D ATA
. [0260] A differential scanning calorimetry curve and thermogravimetric analysis curve of the crystalline solid is provided in FIG.12. A differential scanning calorimetry curve of the crystalline solid is provided in FIG.13. [0261] The crystalline solid was analyzed for water content by KF titration and determined to have a water content of 5.32 wt % (i.e., slightly more than 2 molar equivalents relative to maleate salt). The crystalline solid was analyzed by 1 H NMR spectroscopy and determined to contain 0.20 wt % residual 2-propanol, and a 1.00:1.00 molar ratio of maleic acid : (S)-1-((R)- 3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro -4-methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. [0262] The crystalline solid was analyzed for hygroscopicity. Results of the analysis for hygroscopicity by dynamic vapor sorption are depicted in FIG.14, showing a 0.507% increase in weight when transitioned from 5% to 95% relative humidity. [0263] An accelerated stability study was conducted on the crystalline solid. Approximately 10 mg of crystalline solid was placed into a 4 mL vial, and the vial was covered with a Kimwipe. The vial was stored for one week inside a stability chamber producing a relative humidity of 75% at 40°C. Analysis of the recovered salt by HPLC demonstrated good chemical stability: 99.59 area percent purity before the study, and 99.56 area percent purity after the study. Analysis of the recovered salt by XRPD showed no change of the crystalline form. [0264] This crystalline solid demonstrated water solubility at pH 6.8 and 37°C of 0.87 mg/mL after 30 minutes and >2.0 mg/mL after 24 hours. EXAMPLE 2 -- Preparation of Benzenesulfonic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6- amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3- yl)-2,2-difluoroethan-1-ol [0265] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added benzenesulfonic acid (~1.1 equivalents) in ethanol (~20 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0266] Ethanol was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. No crystalline solid was observed, so the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0267] Methyl isobutyl ketone was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0268] An X-ray powder diffractogram of the crystalline solid is provided in FIG.2. Tabulated characteristics of the X-ray powder diffractogram in FIG.2 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA . [0269] A differential scanning calorimetry curve of the title compound displayed two major endotherms: one endotherm with an onset at 28 degrees Celsius and a peak at 51 degrees Celsius, and a second endotherm with an onset at 109 degrees Celsius and a peak at 134 degrees Celsius. [0270] The crystalline solid was analyzed by 1 H NMR spectroscopy and determined to contain 0.99 wt % residual methyl isobutyl ketone, and a 1.03:1.00 molar ratio of benzenesulfonic acid : (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. [0271] The crystalline solid demonstrated water solubility of 1.49 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. EXAMPLE 3 -- Preparation of p-Toluenesulfonic Acid Salt of (S)-1-((R)-3-amino-1-(4- ((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphe nyl)pyridin-3-yl)piperidin- 3-yl)-2,2-difluoroethan-1-ol [0272] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added p-toluenesulfonic acid monohydrate (~1.1 equivalents) in ethanol (~20 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0273] Ethyl acetate was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0274] An X-ray powder diffractogram of the crystalline solid is provided in FIG.3. Tabulated characteristics of the X-ray powder diffractogram in FIG.3 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA . [0275] A differential scanning calorimetry curve of the title compound displayed an endotherm with an onset at 161 degrees Celsius and a peak at 171 degrees Celsius. [0276] The crystalline solid was analyzed by 1 H NMR spectroscopy and determined to contain a 1.05:1.00 molar ratio of p-toluenesulfonic acid : (S)-1-((R)-3-amino-1-(4-((6-amino- 9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2- difluoroethan-1-ol. [0277] The crystalline solid demonstrated water solubility of 1.61 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. EXAMPLE 4 -- Preparation of Crystalline Form A of 1,2-Ethanedisulfonic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol [0278] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added 1,2-ethanedisulfonic acid (~1.1 equivalents) in ethanol (~20 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0279] Ethanol was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. The mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0280] Methyl isobutyl ketone was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0281] An X-ray powder diffractogram of the title compound is provided in FIG.4. Tabulated characteristics of the X-ray powder diffractogram in FIG.4 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA . [0282] The title compound was analyzed by 1 H NMR spectroscopy and determined to contain no residual solvent above the limit of detection, and an approximate 1.3:1.0 molar ratio of 1,2-ethanedisulfonic acid : (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. EXAMPLE 5 -- Preparation of Crystalline Form B of 1,2-Ethanedisulfonic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol [0283] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added 1,2-ethanedisulfonic acid (~1.1 equivalents) in ethanol (~20 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0284] A mixture of 2-propanol: water (9:1 v/v) was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0285] An X-ray powder diffractogram of the title compound is provided in FIG.5. Tabulated characteristics of the X-ray powder diffractogram in FIG.5 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-R AY P OWDER D IFFRACTOGRAM D ATA
. [0286] The title compound was analyzed by 1 H NMR spectroscopy and determined to contain no residual solvent above the limit of detection, and an approximate 1.3:1.0 molar ratio of 1,2-ethanedisulfonic acid : (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. EXAMPLE 6 -- Preparation of Crystalline Form C of 1,2-Ethanedisulfonic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol [0287] A sample of crystalline Form A of 1,2-ethanedisulfonic acid salt of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl) pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol, prepared as described in Example 4 above, was exposed at room temperature overnight to >95% relative humidity (generated by storing the sample in a sealed chamber also containing a beaker of saturated potassium sulfate in water). The resulting solid was then dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0288] An X-ray powder diffractogram of the title compound is provided in FIG.6. Tabulated characteristics of the X-ray powder diffractogram in FIG.6 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA . [0289] A differential scanning calorimetry curve of the title compound displayed two major endotherms: one endotherm with an onset at 57 degrees Celsius and a peak at 100 degrees Celsius, and a second endotherm with an onset at 232 degrees Celsius and a peak at 243 degrees Celsius. [0290] The title compound was analyzed by 1 H NMR spectroscopy and determined to contain no residual solvent above the limit of detection, and an approximate 1.3:1.0 molar ratio of 1,2-ethanedisulfonic acid : (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. EXAMPLE 7 -- Preparation of D-Gluconic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6- amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3- yl)-2,2-difluoroethan-1-ol [0291] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added D-gluconic acid (~1.1 equivalents) in water (~50 mg acid/mL water). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0292] A mixture of 2-propanol:water (9:1 v/v) was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. No crystalline solid was observed, so the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0293] A mixture of acetonitrile:water (9:1 v/v) was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0294] An X-ray powder diffractogram of the crystalline solid is provided in FIG.7. Tabulated characteristics of the X-ray powder diffractogram in FIG.7 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-R AY P OWDER D IFFRACTOGRAM D ATA . [0295] A differential scanning calorimetry curve of the title compound displayed two major endotherms: one endotherm with an onset at 66 degrees Celsius and a peak at 87 degrees Celsius, and a second endotherm with an onset at 129 degrees Celsius and a peak at 137 degrees Celsius. [0296] The crystalline solid was analyzed by 1 H NMR spectroscopy and determined to contain no residual solvent above the limit of detection, and a 1.06:1.00 molar ratio of D- gluconic acid: (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5-difluoro-4- methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. [0297] The crystalline solid demonstrated water solubility of 0.53 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. EXAMPLE 8 -- Preparation of Gentisic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6-amino- 9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl)pyridi n-3-yl)piperidin-3-yl)-2,2- difluoroethan-1-ol [0298] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added gentisic acid (~1.1 equivalents) in ethanol (~20 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0299] Ethyl acetate was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. No crystalline solid was observed, so the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0300] 2-Propanol was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0301] An X-ray powder diffractogram of the crystalline solid is provided in FIG.8. EXAMPLE 9 -- Preparation of Crystalline Form A of Phosphoric Acid Salt of (S)-1-((R)- 3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro -4-methoxyphenyl)pyridin- 3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol [0302] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added phosphoric acid (~0.55 equivalents) in ethanol (~35 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0303] Ethyl acetate was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0304] An X-ray powder diffractogram of the title compound is provided in FIG.9. Tabulated characteristics of the X-ray powder diffractogram in FIG.9 are provided below in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-R AY P OWDER D IFFRACTOGRAM D ATA . [0305] A differential scanning calorimetry curve of the title compound displayed two major endotherms: one endotherm with an onset at 127 degrees Celsius and a peak at 143 degrees Celsius, and a second endotherm with an onset at 178 degrees Celsius and a peak at 216 degrees Celsius. [0306] The title compound was analyzed by 1 H NMR spectroscopy and determined to contain 0.70 wt % residual ethyl acetate. [0307] The crystalline solid demonstrated water solubility of >2.0 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. EXAMPLE 10 -- Preparation of Crystalline Form B of Phosphoric Acid Salt of (S)-1- ((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-dif luoro-4- methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan -1-ol [0308] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added phosphoric acid (~0.55 equivalents) in ethanol (~35 mg acid/mL ethanol). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0309] A mixture of 2-propanol:water (9:1 v/v) was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. No crystalline solid was observed, so the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0310] A mixture of acetonitrile:water (9:1 v/v) was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0311] An X-ray powder diffractogram of the title compound is provided in FIG.10. Tabulated characteristics of the X-ray powder diffractogram in FIG.10 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA . [0312] A differential scanning calorimetry curve of the title compound displayed two major endotherms: one endotherm with an onset at 62 degrees Celsius and a peak at 100 degrees Celsius, and a second endotherm with an onset at 237 degrees Celsius and a peak at 254 degrees Celsius. [0313] The title compound was analyzed by 1 H NMR spectroscopy and determined to contain 0.09 wt % residual acetonitrile. [0314] The crystalline solid demonstrated water solubility of 0.28 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. EXAMPLE 11 -- Preparation of L-Aspartic Acid Salt of (S)-1-((R)-3-amino-1-(4-((6- amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3- yl)-2,2-difluoroethan-1-ol [0315] To a solution of (S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2 ,5- difluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-di fluoroethan-1-ol (30 mg) in tetrahydrofuran (0.60 mL) in a 2-mL vial with a stir bar was added L-aspartic acid (~1.1 equivalents). The vial was capped, and the mixture was heated with stirring at 40 °C for 2 hours. The cap was removed, and the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0316] Ethanol was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for four days. No crystalline solid was observed, so the mixture was stirred overnight at 40 °C open to the atmosphere. After 24 hours, any remaining solvent was evaporated under a gentle stream of nitrogen at room temperature. The solid was dried under vacuum at 50 °C for at least 3 hours. [0317] Methyl isobutyl ketone was added to form a flowable slurry (at least 0.3 mL), and the mixture was heated with stirring at 45 °C for 2 hours. The mixture was allowed to cool to room temperature and stirred for three days. The precipitated solid was collected and dried under vacuum at 50 °C for at least 3 hours, to provide the title compound as a crystalline solid. [0318] An X-ray powder diffractogram of the crystalline solid is provided in FIG.11. Tabulated characteristics of the X-ray powder diffractogram in FIG.11 are provided in the following table, which lists diffraction angle 2θ, inter-planar distances d, and relative intensity (expressed as a percentage with respect to the most intense peak): X-RAY POWDER DIFFRACTOGRAM DATA
. [0319] A differential scanning calorimetry curve of the title compound displayed three endotherms with the following onset and peak temperatures: 1. Onset at 29 degrees Celsius and a peak at 48 degrees Celsius 2. Onset at 104 degrees Celsius and a peak at 142 degrees Celsius, and 3. Onset at 232 degrees Celsius and a peak at 254 degrees Celsius. [0320] The crystalline solid was analyzed by 1 H NMR spectroscopy and determined to contain 2.22 wt % residual 2-propanol, and a 1.64:1.00 molar ratio of L-aspartic acid : ( ((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-dif luoro-4-methoxyphenyl) pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol. [0321] The crystalline solid demonstrated water solubility of 0.98 mg/mL of (S)-1-((R)-3- amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4 -methoxyphenyl)pyridin-3- yl)piperidin-3-yl)-2,2-difluoroethan-1-ol at pH 7.0 (phosphate buffer) and 37°C after 30 minutes. INCORPORATION BY REFERENCE [0322] The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes. EQUIVALENTS [0323] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.