Crystal of compound having JAK-inhibiting activity
AssigneeNippon Shinyaku Co., Ltd.
InventorFumi Higuchi
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Abstract
An object of the present invention is to provide a compound with an excellent JAK1 inhibitory activity. The compound of the invention has JAK1 inhibitory activity, and thus, immunosuppressive effect, anti-inflammatory effect, anti-proliferative effect and so on, and is useful in the treatment of the diseases, for example, rheumatoid arthritis, inflammatory bowel disease, psoriasis, vasculitis, bronchial asthma, chronic obstructive pulmonary disease, eosinophilic sinusitis and nasal polyp.
Claims12
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of methyl [1-({6-[(2S)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.3°, 20.0°, 20.4°, 21.3° and 22.3°.
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of methyl [1-({6-[(2R)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.3°, 20.0°, 20.4°, 21.3° and 22.3°.
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of methyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.2°, 20.6° and 21.8°.
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of ethyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.0°, 13.8°, 15.0°, 16.0°, 19.4°, 20.9° and 21.9°.
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of N-(1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 11.1°, 12.9°, 15.4°, 17.8°, 21.2° and 22.3°.
A method for treating atopic dermatitis, bronchial asthma, eosinophilic pneumonia, chronic obstructive pulmonary disease, eosinophilic sinusitis, nasal polyp, rheumatoid arthritis, juvenile arthritis, Castleman's disease, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, psoriasis, scleroderma, Takayasu's arteritis, giant cell arteritis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, neuromyelitis optica, eosinophilia, or bone marrow transplant rejection, the method comprising the step of administering as an active ingredient a crystalline form of N-(1-{[6-{[(2R)-3,3-dimethylbutan-2-yl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 10.6°, 13.0°, 14.6°, 17.4°, 17.7°, 21.3° and 21.7°.
A method for producing a crystalline form of methyl [1-({6-[(2S)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.3°, 20.0°, 20.4°, 21.3° and 22.3°, the method comprising the steps of:
- reacting methyl [1-({6-[(2S)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate with p-toluenesulfonic acid monohydrate in acetonitrile while heating;
- and
- subsequently crystallizing methyl [1-({6-[(2S)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate by cooling the acetonitrile solution.
A method for producing a crystalline form of methyl [1-({6-[(2R)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.3°, 20.0°, 20.4°, 21.3° and 22.3°, the method comprising the steps of:
- reacting methyl [1-({6-[(2R)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate with p-toluenesulfonic acid monohydrate in acetonitrile while heating;
- and
- subsequently crystallizing methyl [1-({6-[(2R)-butan-2-ylamino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]carbamate tosylate monohydrate by cooling the acetonitrile solution.
A method for producing a crystalline form of methyl (14 [6-{[(1S)-1-cyclopropylethyl]amino-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate tosylate monohydrate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.6°, 13.3°, 17.2°, 20.6° and 21.8°, the method comprising the steps of:
- reacting methyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate with p-toluenesulfonic acid monohydrate in acetonitrile while heating;
- and
- subsequently crystallizing methyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate tosylate monohydrate by cooling the acetonitrile solution.
A method for producing a crystalline form of ethyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 12.0°, 13.8°, 15.0°, 16.0°, 19.4°, 20.9° and 21.9°, the method comprising the steps of:
- dissolving ethyl (1-{[6-{[(1S)-1-cyclopropylethyl] amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate in ethyl acetate while heating;
- and
- subsequently crystallizing ethyl (1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate by cooling the ethyl acetate solution.
A method for producing a crystalline form of N-(1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 11.1°, 12.9°, 15.4°, 17.8°, 21.2° and 22.3°, the method comprising the steps of:
- dissolving N-(1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide in ethyl acetate while heating;
- and
- subsequently crystallizing N-(1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide by cooling the ethyl acetate solution.
A method for producing a crystalline form of N-(1-{[6-{[(2R)-3,3-dimethylbutan-2-yl] amino}-2-(pyrazolo[5,1-1)] [1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation, which comprises diffraction peaks at diffraction angles (2θ) of 10.6°, 13.0°, 14.6°, 17.4°, 17.7°, 21.3° and 21.7°, the method comprising the steps of:
- dissolving N-(1-{[6-{[(2R)-3,3-dimethylbutan-2-yl] amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide in ethyl acetate while heating;
- and
- subsequently crystallizing N-(1-{[6-{[(2R)-3,3-dimethylbutan-2-yl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl]carbonyl}piperidin-4-yl)cyclopropanecarboxamide by cooling the ethyl acetate solution.
Dependencies are inferred from the claim text.