SOLID FORMS OF (3'-CHLOROBIPHENYL-4-YL)(1-(PYRIMIDIN-2-YL)PIPERIDIN-4-YL)METHANONE AND METHODS OF THEIR USE
Solid amorphous and crystalline forms of (3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone are disclosed, in addition to methods of their use in the treatment of various diseases and disorders.
1 . Solid amorphous (3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone or a pharmaceutically acceptable salt or solvate thereof.
2 - 9 . (canceled)
10 . A crystalline compound, wherein the compound is (3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone or a pharmaceutically acceptable salt or solvate thereof.
11 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises a peak at about 4.7 degrees 2θ.
12 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 9.3 and 18.8 degrees 2θ.
13 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 19.7 and 22.4 degrees 2θ.
14 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 23.2 and 27.9 degrees 2θ.
15 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 29.6 and 32.2 degrees 2θ.
16 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 32.6 and 37.2 degrees 2θ.
17 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 41.6 and 42.3 degrees 2θ.
18 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that comprises peaks at about 9.3, 27.9 and 42.7 degrees 2θ.
19 . The crystalline compound of claim 10 , which has an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1 .
20 . The crystalline compound of claim 10 , which has a Raman spectrum that is substantially the same as that shown in FIG. 2 .
21 . The crystalline compound of claim 10 , which has a melting point of about 117° C.
22 . Solid 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone comprising crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl )piperidin-4-yl)methanone in an amount of at least about 50 weight percent.
23 . The solid of claim 22 , which comprises crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone in an amount of at least about 75 weight percent.
24 . The solid of claim 23 , which comprises crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone in an amount of at least about 95 weight percent.
25 . A method of preparing crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone, which comprises:
dissolving 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone in ethanol to provide a solution;
cooling the solution to a temperature at which crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone forms; and
isolating the crystalline 3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone.
26 . A pharmaceutical dosage form comprising the crystalline compound of claim 10 .
27 - 29 . (canceled)
30 . A method of improving the cognitive performance of a patient, which comprises administering to the patient an effective amount of the crystalline compound of claim 10 .
31 . (canceled)
32 . The method of claim 30 , wherein the cognitive performance is rapidity of learning, comprehension, reasoning, or memory.
33 . A method of treating, managing or preventing a disease or disorder in a patient, which comprises administering to the patient an effective amount of the crystalline compound of claim 10 .
34 . (canceled)
35 . The method of claim 33 , wherein the disease or disorder is Alzheimer's disease, autism, a cognitive disorder, dementia, a learning disorder, or memory loss.
36 . The method of claim 35 , wherein the learning disorder is dyslexia, dyscalculia, dysgraphia, dysphasia, or dysnomia.
37 . A method of preparing a dosage form, which comprises combining crystalline (3′-chlorobiphenyl-4-yl)(1-(pyrimidin-2-yl)piperidin-4-yl)methanone with a pharmaceutically acceptable excipient.
38 . The method of claim 37 , wherein the dosage form is a liquid dosage form.