Crystal form of lipoprotein compound and preparation method therefor
AssigneeJiangsu Hengrui Pharmaceuticals Co., Ltd.
InventorsJiaqi YAO, Junran YANG, Zhenxing DU, Jie WANG
Life of this patent
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Abstract
The present disclosure relates to a crystal form of a lipoprotein compound and a preparation method therefor. Specifically, the present disclosure provides a crystal form of (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid and a preparation method therefor.
Claims28
A crystal form A of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl) amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 8.343, 18.020, and 21.028, preferably having characteristic peaks at 8.343, 12.559, 15.612, 18.020, and 21.028, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 2.
A crystal form B of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl) amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 7.794, 15.530, 19.456, 20.559, and 21.500, preferably having characteristic peaks at 7.794, 11.832, 15.530, 19.456, 20.559, 21.500, and 29.097, more preferably having characteristic peaks at 7.794, 11.832, 12.642, 15.530, 19.456, 20.559, 21.500, and 29.097, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 3.
A crystal form C of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl) amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 8.547, 8.847, 13.567, 15.576, and 19.169, preferably having characteristic peaks at 8.547, 8.847, 10.487, 13.567, 15.576, and 19.169, more preferably having characteristic peaks at 8.547, 8.847, 10.487, 13.567, 15.576, 19.169, and 21.973, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 4.
A crystal form D of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl) amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 13.834, 16.316, and 20.830, preferably having characteristic peaks at 7.928, 13.834, 16.316, and 20.830, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 5.
A pharmaceutically acceptable salt of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, wherein the pharmaceutically acceptable salt is selected from hydrochloride, succinate, meglumine salt, maleate, hippurate, sulfate, phosphate, methanesulfonate, tartrate, fumarate, citrate, sodium salt, potassium salt and arginine salt.
A potassium salt crystal form α of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 5.544, 8.016, and 19.356, preferably having characteristic peaks at 5.544, 8.016, 19.356, and 21.537, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 6.
An arginine salt crystal form a of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 8.191, 10.598, 15.844, 18.447, and 20.119, preferably having characteristic peaks at 8.191, 10.598, 15.844, 18.447, 20.119, and 24.226, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 7.
A sodium salt crystal form I of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 13.831 and 18.556, preferably having characteristic peaks at 7.834, 13.831, 16.194, and 18.556, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 8.
A meglumine salt crystal form a of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 5.361, 5.879, 7.118, 8.069, 8.827, and 19.069, preferably having characteristic peaks at 5.361, 5.879, 7.118, 8.069, 8.827, 9.748, 16.230, and 19.069, more preferably having characteristic peaks at 5.361, 5.879, 7.118, 8.069, 8.827, 9.748, 13.795, 16.230, 19.069, 21.864, and 26.223, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 9.
A maleate crystal form a of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 7.907, 15.612, 19.174, and 20.701, and preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 10.
A hippurate crystal form a of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 5.551, 9.410, 13.522, 14.534, 19.956, 21.337, and 22.945, preferably having characteristic peaks at 5.551, 9.410, 11.209, 13.522, 14.175, 14.534, 19.956, 21.022, 21.337, and 22.945, more preferably having characteristic peaks at 5.551, 9.410, 11.209, 13.522, 14.175, 14.534, 16.709, 19.956, 21.022, 21.337, and 22.945, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 11.
A hippurate crystal form β of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 4.944, 14.737, 17.143, and 20.109, preferably having characteristic peaks at 4.944, 9.978, 14.737, 17.143, and 20.109, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 12.
A hydrochloride crystal form a of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 6.385, 13.533, 16.203, and 21.244, preferably having characteristic peaks at 6.385, 8.530, 13.533, 16.203, and 21.244, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 13.
A hydrochloride crystal form b of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 8.059, 10.359, 19.412, 20.726, and 21.843, preferably having characteristic peaks at 8.059, 10.359, 16.017, 17.806, 19.412, 20.726, and 21.843, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 14.
A hydrochloride crystal form c of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 9.395, 11.238, 13.495, and 20.153, preferably having characteristic peaks at 9.395, 11.238, 13.495, 20.153, 21.169, and 23.125, and more preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 15.
A hydrochloride crystal form d of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 8.128, 12.995, 14.962, 16.354, 20.401, and 23.032, preferably having characteristic peaks at 8.128, 12.216, 12.995, 14.962, 16.354, 19.268, 20.401, and 23.032, more preferably having characteristic peaks at 8.128, 12.216, 12.995, 14.962, 16.354, 19.268, 19.965, 20.401, 23.032, and 24.742, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 16.
A hydrochloride crystal form e of compound (2S)-3-(3-{[(2-{3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenoxy}ethyl)({3-[(2S)-2-carboxyl-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl}methyl)amino]methyl}phenyl)-2-[(3R)-pyrrolidin-3-yl]propionic acid, characterized by an X-ray powder diffraction pattern represented by a diffraction angle 2θ having characteristic peaks at 9.385, 14.145, 19.709, 20.277, and 21.583, preferably having characteristic peaks at 9.385, 14.145, 15.451, 19.709, 20.277, 21.583, and 23.684, more preferably having characteristic peaks at 9.385, 14.145, 15.451, 19.709, 20.277, 21.583, 23.187, 23.684, and 24.366, and most preferably an X-ray powder diffraction pattern represented by a diffraction angle 2θ as shown in FIG. 17.
Dependencies are inferred from the claim text.