Pharmaceutically acceptable salt and crystalline form of glp-1 receptor agonist and preparation method therefor
AssigneesJiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai Hengrui Pharmaceutical Co., Ltd.
InventorsWeidong LU, Gujun XU, Junran YANG, Qiyun SHAO, Zhenxing DU, Jun FENG, Feng HE
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Abstract
Provided are a pharmaceutically acceptable salt and a crystalline form of a GLP-1 receptor agonist and a preparation method therefor. Specifically, provided are a pharmaceutically acceptable salt and a crystalline form of a compound 2-((4-((S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxane-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxe-tane-2-yl)methyl)-1H-benzo[d]imidazole-6-formic acid.
Claims21
A pharmaceutically acceptable salt of compound 2-((4-((S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt.
Crystal form A, B, C, D, E or F of a tromethamine salt of compound 2-((4-((S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, wherein (1) an X-ray powder diffraction pattern of the crystal form A expressed with diffraction angle 2θ has characteristic peaks at 6.850, 9.982, 13.789, 16.148, and 22.138;
- preferably characteristic peaks at 6.850, 9.982, 12.697, 13.789, 15.763, 16.148, 18.016, 19.016, and 22.138;
- more preferably characteristic peaks at 6.850, 8.051, 9.982, 12.697, 13.789, 14.704, 14.990, 15.763, 16.148, 18.016, 19.016, 20.109, 22.138, 25.712, and 27.909;
- most preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 2;
- (2) an X-ray powder diffraction pattern of the crystal form B expressed with diffraction angle 2θ has characteristic peaks at 8.144, 10.511, 12.290, 20.632, and 21.699:
- preferably characteristic peaks at 8.144, 10.511, 12.290, 13.996, 14.665, 20.632, 21.699, and 24.743:
- more preferably characteristic peaks at 8.144, 10.511, 12.290, 13.996, 14.665, 15.607, 16.520, 18.883, 20.632, 21.699, 23.741, 24.743, 26.055, and 27.035:
- most preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 3;
- (3) an X-ray powder diffraction pattern of the crystal form C expressed with diffraction angle 2θ has characteristic peaks at 6.551, 9.269, 13.175, and 16.906:
- preferably characteristic peaks at 6.551, 9.269, 13.175, 14.802, 15.864, 16.906, 18.776, 20.430, and 25.496:
- more preferably characteristic peaks at 6.551, 8.392, 9.269, 13.175, 14.802, 15.864, 16.906, 18.776, 20.430, 22.211, 22.922, 23.574, 25.496, and 26.290;
- most preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 4;
- (4) an X-ray powder diffraction pattern of the crystal form D expressed with diffraction angle 2θ has characteristic peaks at 5.281, 10.292, 13.322, and 21.390:
- preferably characteristic peaks at 5.281, 9.912, 10.292, 10.961, 13.322, 21.390, 22.215, 23.979, 25.029, and 25.846;
- more preferably characteristic peaks at 5.281, 9.912, 10.292, 10.961, 11.613, 13.322, 15.351, 18.283, 19.214, 21.390, 22.215, 23.471, 23.979, 25.029, 25.846, 27.918, and 30.121:
- most preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 5;
- (5) an X-ray powder diffraction pattern of the crystal form E expressed with diffraction angle 2θ has characteristic peaks at 6.821, 10.035, 12.653, 13.727, and 14.787:
- preferably characteristic peaks at 6.821, 10.035, 12.653, 13.727, 14.787, 16.081, 16.648, 18.571, 20.151, and 22.204:
- more preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 6;
- and
- (6) an X-ray powder diffraction pattern of the crystal form F expressed with diffraction angle 2θ has characteristic peaks at 7.674, 10.614, 16.400, and 18.645:
- preferably characteristic peaks at 6.777, 7.674, 10.614, 11.594, 14.408, 14.882, 16.400, and 18.645:
- more preferably characteristic peaks at 6.777, 7.674, 10.614, 11.594, 13.671, 14.408, 14.882, 16.400, 18.645, 20.849, 21.384, 21.731, 22.108, 24.721, 26.169, and 29.192:
- most preferably, the X-ray powder diffraction pattern expressed with diffraction angle 2θ is as shown in FIG. 7.
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Dependencies are inferred from the claim text.