Processes and polymorphs of diaryl-indolone galr3 antagonists
This invention relates to crystalline forms, as well as an amorphous form of Compound I [1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-1H-indol-2-one], the processes for their preparation, compositions containing the same and the therapeutic use of such compositions. This invention further relates to a process for preparing Compound I.
1 . A crystalline form I of compound I having an X-ray powder diffraction pattern comprising the following 2θ value measured using CuKα radiation: 6.3.
2 . A crystalline Form I of Compound I having an X-ray powder diffraction pattern comprising the following 2θ values measured using CuKα radiation: 6.3, 19.0 and 25.5.
3 . A crystalline Form I of Compound I of claim 2 diffraction pattern further comprising the following 2θ values: 12.7, 22.0, 24.9 and 38.6.
4 . A crystalline Form I of Compound I having an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 1 a as measured using CuKα radiation.
5 . A crystalline Form I of Compound I having differential scanning calorimetric curves substantially similar to those set forth in FIG. 3 .
6 . A crystalline Form I of Compound I having differential scanning calorimetric curves comprising one endotherm at approximately 141° C. and one endotherm at approximately 143° C., as measured at a ramp rate of 1° C./min.
7 . A crystalline Form I of Compound I having a Fourier transform infrared pattern comprising at least one of the following infrared peaks: 3462, 3285, 3106, 2770, 2752, 1991, 1882, 1747, 1696, 656, 1651, 1332, 1253 and 557.
8 . A crystalline Form I of Compound having a Raman peak pattern comprising at least one of the following peaks: 1739 and 1653, as measured using a spectrometer.
9 . A pharmaceutical composition useful for treatment of a human disease comprising crystalline Form I of Compound I and a pharmaceutically acceptable carrier.
10 . The composition of claim 9 , wherein a substantial percentage of Compound I is present as Form I.
11 . The composition of claim 9 , wherein at least 99.9% of Compound I is present as Form I.
12 . The composition of claim 9 , wherein at least 98% of Compound I is present as crystalline Form I.
13 . The composition of claim 9 , wherein at least 95% of Compound I is present as crystalline Form I.
14 . The composition of claim 9 , wherein at least 90% of Compound I is present as crystalline Form I.
15 . The composition of claim 9 , wherein at least 85% of Compound I is present as crystalline Form I.
16 . The composition of claim 9 , wherein at least 80% of Compound I is present as crystalline Form I.
17 . The composition of claim 9 , wherein the disease is depression or anxiety.
18 . A process for preparation of a pharmaceutical composition, comprising admixing Form I of Compound I with a pharmaceutically acceptable carrier.
19 . The process of claim 18 , further comprising obtaining Form I of Compound I of substantial purity.
20 . A method for treatment of a human disease, wherein the method comprises administering to a human subject suffering such disease a therapeutically effective amount of crystalline Form I of Compound I.
21 . The method of claim 20 , wherein the disease is a CNS disorder.
22 . The method of claim 20 , wherein the disease is anxiety or depression.
23 . A process of preparing of crystalline Form I of Compound I, comprising stirring a slurry of Compound I in a solvent for a period of time of no less than one hour.
24 . The process of claim 23 , wherein the solvent is selected from a group consisting of toluene, heptane, meta-xylene, ortho-xylene, para-xylene, isopropyl acetate, methanol, ethanol, 1-butanol, 1-octanol.
25 . A crystalline Form III of Compound I having an X-ray powder diffraction pattern comprising at least one of the following 2θ values measured using CuKα radiation: 6.1 and 21.2.
26 - 93 . (canceled)