CRYSTALLINE FORMS OF A RIPK1 INHIBITOR
The present invention provides a crystalline compound of the formula: wherein the crystalline compound is useful for treating autoimmune and inflammatory diseases, such as atopic dermatitis, rheumatoid arthritis, and psoriasis.
1 . A crystalline form of a compound of the formula:
2 . The crystalline form of claim 1 , which is a crystalline anhydrate.
3 . The crystalline form of claim 2 , which is characterized by at least one of the following:
a) an X-ray powder diffraction pattern using CuKα radiation comprising a peak at diffraction angle 2-theta of 7.0° and one or more peaks at 11.2°, 17.4°, or 19.5°, with a tolerance for the diffraction angles of ±0.2 degrees; and
b) a 13 C solid state NMR spectrum which comprises peaks referenced to the highfield resonance of adamantane (δ=29.5 ppm) at: 168.5, 159.7, 157.4, 156.0, 149.5, 138.5, 136.6, 129.7, 129.1, 127.5, 126.6, 123.5, 121.9, 98.5, 79.8, 77.2, 65.8, 49.1, 36.4, 34.9, 32.5, and 30.5 ppm (±0.2 ppm respectively).
4 . The crystalline form of claim 2 , which is characterized by at least one of the following:
a) an X-ray powder diffraction pattern using CuKα radiation comprising a peak at diffraction angle 2-theta of 7.0° and one or more peaks at 11.2°, 16.9°, 17.4°, or 19.5°, with a tolerance for the diffraction angles of ±0.2 degrees and
b) a 13 C solid state NMR spectrum which comprises peaks referenced to the highfield resonance of adamantane (δ=29.5 ppm) at: 168.5, 159.7, 157.4, 156.0, 149.5, 138.5, 136.6, 129.7, 129.1, 127.5, 126.6, 123.5, 121.9, 98.5, 79.8, 77.2, 65.8, 49.1, 36.4, 34.9, 32.5, and 30.5 ppm (±0.2 ppm respectively).
5 . The crystalline form of claim 2 , which is characterized by at least one of the following:
a) an X-ray powder diffraction pattern using CuKα radiation comprising a peak at diffraction angle 2-theta of 7.0° and one or more peaks at 11.2°, 15.1°, 16.9°, 17.4°, or 19.5°, with a tolerance for the diffraction angles of ±0.2 degrees; and
b) a 13 C solid state NMR spectrum which comprises peaks referenced to the highfield resonance of adamantane (δ=29.5 ppm) at: 168.5, 159.7, 157.4, 156.0, 149.5, 138.5, 136.6, 129.7, 129.1, 127.5, 126.6, 123.5, 121.9, 98.5, 79.8, 77.2, 65.8, 49.1, 36.4, 34.9, 32.5, and 30.5 ppm (±0.2 ppm respectively).
6 . The crystalline form according to claim 2 characterized by an X-ray powder diffraction pattern using CuKα radiation comprising a peak at diffraction angle 2-theta of 17.5° and one or more peaks at 9.7°, 14.4°, 15.4°, 17.0°, or 17.9°, with a tolerance for the diffraction angles of ±0.2 degrees.
7 . The crystalline form according to claim 2 characterized by an X-ray powder diffraction pattern using CuKα radiation comprising a peak at diffraction angle 2-theta of 18.1° and one or more peaks at 9.9°, 11.5°, 12.2°, 14.7°, or 16.5°, with a tolerance for the diffraction angles of ±0.2 degrees.
8 . A method of treating an inflammatory disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
9 . A method of treating an autoimmune disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
10 . A method of treating psoriasis in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
11 . A method of treating atopic dermatitis in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
12 . A method of treating rheumatoid arthritis in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
13 - 23 . (canceled)
24 . A pharmaceutical composition, comprising a crystalline form according to claim 3 with one or more pharmaceutically acceptable carriers, diluents, or excipients.
25 . (canceled)
26 . A method of treating an inflammatory bowel disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 3 .
27 . A method of treating an inflammatory or autoimmune disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 6 .
28 . A method of treating psoriasis, atopic dermatitis, rheumatoid arthritis, or inflammatory bowel disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 6 .
29 . A method of treating an inflammatory or autoimmune disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 7 .
30 . A method of treating psoriasis, atopic dermatitis, rheumatoid arthritis, or inflammatory bowel disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 7 .
31 . A method of treating an inflammatory or autoimmune disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 5 .
32 . A method of treating psoriasis, atopic dermatitis, rheumatoid arthritis, or inflammatory bowel disease in a patient, comprising administering to a patient in need of such treatment an effective amount of a crystalline form according to claim 5 .