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Bristol-Myers Squibb Co.
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Building IP: BMY Patent Application re "CRYSTAL FORM OF 6-(CYCLOPROPANECARBOXAMIDO)..
CRYSTAL FORM OF 6-(CYCLOPROPANECARBOXAMIDO)-4-((2-METHOXY-3-(1-METHYL-1H-1,2,4-TRIAZOL-3-- YL)PHENYL)AMINO)-N-(METHYL-D3)PYRIDAZINE-3-CARBOXAMIDE Disclosed is crystalline Form E of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide. Form E is a neat crystalline form. Characterization data for Form E are disclosed.
1. Crystalline Form E of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide. 2. The crystalline form according to claim 1 characterized by at least one of the following: (i) unit cell parameters substantially equal to the following: a=10.41.+-.0.10 .ANG. b=12.65.+-.0.10 .ANG. c=15.70.+-.0.10 .ANG. .alpha.=90.0.degree. .beta.=103.5.+-.1.0.degree. .gamma.=90.0.degree. Space group: P2.sub.1/n Molecules per unit cell (Z): 4, wherein the unit cell parameters of Form E of Compound (I) are measured at a temperature of about 100 K; (ii) a powder X-ray diffraction pattern comprising two or more 2 .theta. values in degrees (CuK.alpha.) selected from: 9.0.+-.0.2, 11.3.+-.0.2, 15.2.+-.0.2, and 21.1.+-.0.2, wherein the PXRD pattern is measured at room temperature; (iii) an observed powder X-ray diffraction pattern substantially as shown in FIG. 1, wherein the PXRD pattern is measured at room temperature; or (iv) an endotherm with peak max in the range of from about 249.degree. C. to about 253.degree. C. 3. The crystalline form according to claim 1 characterized by a powder X-ray diffraction (PXRD) pattern comprising three or more 2 .theta. values in degrees (CuK.alpha.) selected from: 9.0.+-.0.2, 11.3.+-.0.2, 15.2.+-.0.2, and 21.1.+-.0.2, wherein the PXRD pattern of the crystalline form is measured at room temperature. 4. The crystalline form according to claim 1 characterized by a powder X-ray diffraction pattern comprising the 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2, 11.3.+-.0.2, 15.2.+-.0.2, and 21.1.+-.0.2, wherein the PXRD pattern of the crystalline form is measured at room temperature. 5. The crystalline form according to claim 1 characterized by: (i) a powder X-ray diffraction pattern comprising the 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2 and 11.3.+-.0.2, measured at room temperature; and (ii) an endotherm with peak max in the range of from about 249.degree. C. to about 253.degree. C. 6. The crystalline form according to claim 1 characterized by: (i) a powder X-ray diffraction pattern comprising the 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2, 11.3.+-.0.2, 15.2.+-.0.2, and 21.1.+-.0.2, measured at room temperature; and (ii) an endotherm with peak max in the range of from about 249.degree. C. to about 253.degree. C. 7. The crystalline form according to claim 1 characterized by: (i) a powder X-ray diffraction pattern comprising the 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2 and 11.3.+-.0.2, measured at room temperature; and (ii) a differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 2. 8. The crystalline form according to claim 1 characterized by: (i) a powder X-ray diffraction pattern comprising the 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2, 11.3.+-.0.2, 15.2.+-.0.2, and 21.1.+-.0.2, measured at room temperature; and (ii) a differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 2. 9. The crystalline form according to claim 1 characterized by a mass increase of less than about 0.1% when subjected to an increase in relative humidity from about 5% to about 95%. 10. The crystalline form according to claim 1 characterized by a thermal gravimetric analysis plot comprising a mass loss of less than about 0.1% when heated from about 30 .degree. C. to about 150.degree. C. 11. The crystalline form according to claim 1 wherein said Form E is in substantially pure form. 12. The crystalline form according to claim 1 characterized by an observed powder X-ray diffraction pattern substantially as shown in FIG. 1. 13. A composition comprising 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxandde, wherein at least 90 weight % of said 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide is in crystalline Form E. 14. The composition according to claim 13, wherein at least 95 weight % of said 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-tr- iazol-3-yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide is in crystalline Form E. 15. A composition comprising crystalline 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide, wherein at least 95 weight % of said crystalline 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide is crystalline Form E. 16. A composition comprising 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide, wherein said 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide consists essentially of crystalline Form E. 17. A pharmaceutical composition comprising the crystalline form according to claim 1 and a pharmaceutically acceptable carrier or diluent. 18. A pharmaceutical composition comprising crystalline Form E of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl) amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide and a pharmaceutically acceptable carrier or diluent, wherein said crystalline Form E is characterized by a powder X-ray diffraction pattern comprising 2 .theta. values in degrees (CuK.alpha.) at 9.0.+-.0.2 and 11.3.+-.0.2, when measured at room temperature. 19. (canceled) FIELD OF THE INVENTION [0001] The present invention generally relates to a crystalline form of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl)amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide. The present invention also generally relates to pharmaceutical compositions comprising the crystalline form, as well methods for obtaining such crystalline form. BACKGROUND OF THE INVENTION [0002] The compound, 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-- yl)phenyl)amino)-N-(methyl-d.sub.3)pyridazine-3-carboxamide, has the structure of Formula (I): ##STR00001## and is referred to herein as "Compound (I)". Compound (I) is disclosed in U.S. Pat. No. RE47,929 E, which is assigned to the present assignee. U.S. Pat. No. RE47,929 E also discloses methods of treatment employing Compound (I). Compound (I) is also known as Deucravacitinib. [0003] Compound (I) is a Tyk2 inhibitor currently in clinical trials for the treatment of autoimmune and auto-inflammatory diseases such as psoriasis, psoriatic arthritis, lupus, lupus nephritis, Sjogren's syndrome, inflammatory bowel disease, Crohn's disease, and ankylosing spondylitis. [0004] In the synthesis of a chemical compound intended for pharmaceutical use, it is necessary to isolate and purify the compound at the completion of the synthetic process and prior to further processing to provide the compound in a pharmaceutical formulation. The isolation and the purification steps, which can be combined or separate consecutive steps, provide the compound as a purified solid, ideally with minimal loss of yield during isolation of the compound from other components of the reaction mixture and/or during purification to remove impurities from the isolated compound sample. [0005] It is desirable to provide a solid form of such a compound that can be reproducibly produced from the isolation and/or purification steps. [0006] Further, it is desirable to isolate the compound in a solid form that is physically and chemically stable upon storage, including at different conditions of temperature and humidity. It is also advantageous to provide the compound in a solid form that exhibits little loss upon storage, and low moisture uptake. [0007] It is also desirable to provide a compound in a solid form that is amenable to additional processing, for example a crystalline form that can be converted to other solid forms, such as an amorphous form or other crystalline forms. [0008] As described herein, a crystalline form of Compound (I) surprisingly provides Compound (I) in a solid form that is physically and chemically stable at a range of storage conditions. This crystalline form also is surprisingly amenable to additional processing and can be converted to other solid forms. In addition, the crystalline form has sufficient solubility in solvents/solutions to permit preparation of other solid forms. The present invention is directed to these and other important aspects. SUMMARY OF THE INVENTION [0009] The present invention provides crystalline Form E of Compound (I). The name used herein to characterize a specific form, e.g. "Form E", should not be considered limiting with respect to any other substance possessing similar or identical physical and chemical characteristics, but rather it should be understood that this designation is a mere identifier that should be interpreted according to the characterization information also presented herein. |
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