Crystal of thyroid hormone B receptor agonist, process for preparing the same and use thereof
Disclosed are crystal of thyroid hormone β receptor agonist, process for preparing the same and use thereof. The crystal with basically no hygroscopicity, a relatively small crystal particle size and a relatively large drug specific surface area can improve the dissolution rate of drugs, is beneficial to the absorption of drugs and improves the bioavailability.
1 . A crystal of a compound of formula I, having diffraction peaks at 2θ angles using Cu-Kα radiation of 12.124±0.2, 15.483±0.2, 16.38±0.2, 16.666±0.2, 19.089±0.2, 20.415±0.2, and 20.821±0.2 in an X-ray power diffraction pattern,
2 . The crystal of claim 1 , having diffraction peaks at 2θ angles using Cu-Kα radiation of 7.951±0.2, 12.124±0.2, 13.555±0.2, 15.483±0.2, 16.017±0.2, 16.38±0.2, 16.666±0.2, 19.089±0.2, 20.415±0.2, 20.821±0.2, 21.764±0.2, 22.34±0.2, 22.628±0.2, 24.055±0.2, and 26.426±0.2 in an X-ray powder diffraction pattern.
3 . The crystal of claim 1 , having an endothermic peak at 111.92° C. when subject to thermal analysis using differential scanning calorimetry.
4 . A process for preparing a crystal of claim 1 , comprising
(1) dissolving an amorphous compound of formula I in a first solvent to precipitate a solvate of the compound of formula I; and
(2) dissolving the solvate obtained in step (1) in a second solvent, and triturating and/or crystallizing to obtain the crystal;
wherein the first solvent is selected from the group consisting of C 1 -C 4 lower alcohols; C 3 -C 6 lower ketones; acetonitrile; methyl tert-butyl ether; diisopropyl ether; C 5 -C 8 linear and branched alkanes; C 5 -C 8 cycloalkanes; and a mixture of any two or more thereof; and
wherein the second solvent is selected from the group consisting of C 1 -C 4 lower alcohols; C 3 -C 6 lower ketones; and a mixture of any two or more thereof.
5 . A process for preparing a crystal of claim 1 , comprising:
(1) dissolving an amorphous compound of formula I in a first solvent to precipitate a solvate of the compound of formula I; and
(2) triturating the solvate obtained in step (1) to obtain the crystal;
wherein the first solvent is selected from the group consisting of C 1 -C 4 lower alcohols; C 3 -C 6 lower ketones; acetonitrile; methyl tert-butyl ether; diisopropyl ether; C 5 -C 8 linear and branched alkanes; C 5 -C 8 cycloalkanes; and a mixture of any two or more thereof.
6 . The process of claim 4 , wherein the triturating and/or crystallizing is carried out in a third solvent.
7 . The process of claim 4 , wherein the triturating is carried out under negative pressure and/or stirring, and/or the crystallizing is carried out under stirring.
8 . The process of claim 4 , wherein concentration is carried out under reduced pressure before the crystallizing.
9 . A pharmaceutical composition comprising the crystal of claim 1 , and optionally a pharmaceutically acceptable excipient.
10 . A method for treating non-alcoholic steatohepatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the crystal of claim 1 .
11 . The crystal of claim 1 , having an X-ray powder diffraction pattern at 2θ angles using Cu-Kα radiation as shown in FIG. 1 , FIG. 1 .
12 . The process of claim 4 , wherein the first solvent is selected from the group consisting of methyl tert-butyl ether, ethanol, and a mixture thereof.
13 . The process of claim 4 , wherein the second solvent is selected from the group consisting of methanol, ethanol, acetone, isopropanol, and a mixture of any two or more thereof.
14 . The process of claim 5 , wherein the first solvent is selected from the group consisting of methyl tert-butyl ether, ethanol, and a mixture thereof.
15 . The process of claim 6 , wherein the third solvent is selected from the group consisting of water, ethanol, and a mixture thereof.
16 . The process of claim 5 , wherein the triturating is carried out in a third solvent.
17 . The process of claim 16 , wherein the third solvent is selected from the group consisting of water, ethanol, and a mixture thereof.
18 . The process of claim 5 , wherein the triturating is carried out under negative pressure and/or stirring.