Solid form of pyrrolidone derivative as glucokinase activator

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form A of a hydrochloride of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.1±0.2, 15.3±0.2, and 18.5±0.2;
• optionally, wherein the crystal form A further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 8.1±0.2, 10.6±0.2, 11.9±0.2, 22.1±0.2, and 22.9±0.2;
• and/or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 12.2±0.2, 17.9±0.2, 21.5±0.2, and 24.9±0.2;
• or
• iii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.06
• 86.1
• 8.11
• 30.3
• 10.61
• 36.7
• 11.89
• 39.2
• 12.18
• 23.0
• 15.27
• 66.8
• 15.66
• 19.5
• 16.28
• 12.1
• 16.68
• 20.0
• 17.89
• 29.9
• 18.45
• 100.0
• 19.45
• 12.6
• 20.41
• 15.7
• 21.51
• 23.7
• 22.14
• 32.6
• 22.94
• 32.0
• 23.75
• 5.8
• 24.94
• 26.0
• 26.89
• 21.1
• 27.53
• 11.9
• 28.23
• 9.8
• 30.64
• 6.5;
• or
• iv) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 9;
• and/or
• v) characterized in that it has endothermic peaks at 125.9±2° C. and 177.8±2° C. in differential scanning calorimetry analysis;
• and/or
• vi) characterized in that it has a weight loss of 4.91±0.5% at 150° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form B of a hydrochloride of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.5±0.2, 18.1±0.2, and 21.4±0.2;
• optionally, wherein the crystal form B further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 11.1±0.2 and 21.7±0.2;
• and/or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 8.7±0.2, 13.7±0.2, 14.4±0.2, 15.1±0.2, and 23.2±0.2;
• or
• iii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.46
• 66.9
• 8.73
• 26.1
• 11.09
• 38.6
• 13.66
• 21.8
• 14.35
• 27.7
• 15.07
• 28.4
• 16.46
• 19.0
• 17.44
• 18.9
• 18.13
• 70.4
• 18.83
• 17.6
• 21.35
• 100.0
• 21.67
• 44.8
• 22.19
• 14.1
• 23.17
• 21.4
• 24.36
• 13.4
• 25.43
• 7.4
• 25.96
• 14.7
• 26.78
• 13.9
• 27.47
• 11.4
• 28.37
• 10.4
• 29.50
• 6.5
• 30.36
• 5.8
• 31.35
• 8.7
• 32.34
• 7.2
• 34.95
• 6.7;
• or
• iv) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 22;
• and/or
• v) characterized in that it has endothermic peaks at 123.1±2° C., 135.2=2° C., and 187.5±2° C. in differential scanning calorimetry analysis;
• and/or
• vi) characterized in that it has a weight loss of 1.32±0.5% at 70° C., and a weight loss of 5.32±0.5% at 70 to 150° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form C of a hydrochloride of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 8.2±0.2, 10.6±0.2, 13.4±0.2, and 20.2±0.2;
• optionally, wherein the crystal form C further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 16.8±0.2 and 17.7±0.2;
• and/or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 4.1±0.2, 8.8±0.2, and 12.2±0.2;
• or
• iii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.11
• 24.8
• 8.16
• 78.6
• 8.78
• 28.8
• 10.61
• 100.0
• 12.24
• 32.4
• 12.52
• 17.6
• 13.41
• 71.0
• 15.05
• 16.2
• 16.78
• 48.8
• 17.72
• 57.7
• 19.06
• 8.8
• 20.22
• 60.2
• 21.52
• 18.1
• 24.64
• 19.7
• 26.66
• 20.6
• 27.73
• 21.7;
• or
• iv) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 24;
• and/or
• v) characterized in that it has endothermic peaks at 60.7±2° C., 114.4±2° C., and 182.4±2° C. in differential scanning calorimetry analysis;
• and/or
• vi) characterized in that it has a weight loss of 5.53±0.5% at 80° C., and a weight loss of 6.72±0.5% at 80 to 150° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form A of a maleate of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 6.0±0.2 and 18.4±0.2;
• optionally, wherein the crystal form A further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 10.4±0.2, 15.9±0.2, and 17.4±0.2;
• and/or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 6.9±0.2, 12.0±0.2, 21.2±0.2, and 21.8±0.2;
• or
• iii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 6.01
• 100.0
• 6.92
• 12.6
• 10.41
• 18.6
• 12.01
• 12.2
• 15.93
• 17.4
• 17.38
• 30.8
• 18.42
• 57.6
• 19.46
• 8.1
• 21.21
• 12.1
• 21.76
• 14.4
• 22.93
• 5.1;
• or
• iv) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 11.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form B of a maleate of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.1±0.2, 8.1±0.2, 16.7±0.2, and 20.2±0.2;
• optionally, wherein the crystal form B further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 17.5±0.2 and 21.3±0.2;
• and/or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 16.2±0.2, 20.4±0.2, 22.4±0.2, 24.1±0.2, 24.6±0.2, and 26.5±0.2;
• or
• iii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.08
• 79.3
• 8.13
• 94.1
• 10.50
• 21.5
• 12.20
• 27.7
• 13.31
• 13.4
• 15.01
• 21.4
• 16.24
• 31.0
• 16.68
• 72.3
• 17.54
• 60.1
• 18.37
• 12.5
• 20.17
• 100.0
• 20.41
• 34.0
• 21.34
• 67.4
• 22.40
• 34.6
• 22.69
• 26.7
• 23.16
• 13.7
• 24.14
• 49.6
• 24.56
• 30.9
• 25.97
• 21.7
• 26.55
• 34.4
• 27.59
• 20.4
• 29.90
• 15.4;
• or
• iv) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 12;
• and/or
• v) characterized in that it has an endothermic peak at 85.6±2° C. in differential scanning calorimetry analysis;
• and/or
• vi) characterized in that it has a weight loss of 12.02±0.5% at 120° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form A of a naphthalene disulfonate of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.0±0.2 and 13.7±0.2;
• optionally, wherein the crystal form A further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 10.3±0.2, 15.5±0.2, 21.0±0.2, and 22.3±0.2;
• or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.03
• 100.0
• 10.28
• 31.9
• 11.96
• 12.6
• 13.68
• 67.6
• 15.49
• 28.7
• 20.96
• 22.4
• 22.27
• 28.0
• 26.22
• 15.1;
• or
• iii) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 14;
• and/or
• iv) characterized in that it has endothermic peaks at 119.2±2° C. and 207.9±2° C. in differential scanning calorimetry analysis;
• and/or
• v) characterized in that it has a weight loss of 5.97±0.5% at 150° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form A of an oxalate of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 5.0±0.2 and 15.0±0.2;
• optionally, wherein the crystal form A further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 7.4±0.2, 16.5±0.2, 19.3±0.2, 20.1±0.2, 25.2±0.2, and 26.0±0.2;
• or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 5.00
• 100.0
• 7.37
• 35.6
• 15.05
• 60.5
• 16.52
• 41.7
• 17.39
• 12.7
• 18.63
• 8.7
• 19.31
• 27.4
• 20.10
• 28.4
• 20.68
• 13.3
• 22.72
• 14.7
• 25.21
• 25.8
• 26.02
• 21.2;
• or
• iii) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 16;
• and/or
• iv) characterized in that it has endothermic peaks at 131.4±2° C. and 192.8±2° C. in differential scanning calorimetry analysis;
• and/or
• v) characterized in that it has a weight loss of 3.91±0.5% at 150° C. in thermogravimetric analysis.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form A of a hydrobromide of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.3±0.2 and 8.3±0.2;
• optionally, wherein the crystal form A further has any one of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 12.4±0.2, 17.5±0.2, 17.9±0.2, 20.5±0.2, and 21.3±0.2;
• or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.26
• 42.7
• 8.29
• 100.0
• 10.63
• 5.4
• 12.42
• 29.3
• 14.81
• 19.3
• 16.53
• 11.4
• 16.86
• 19.9
• 17.53
• 26.9
• 17.90
• 22.6
• 20.50
• 32.3
• 21.31
• 35.0
• 22.52
• 9.6
• 22.96
• 9.1
• 24.60
• 9.8
• 24.96
• 12.8;
• or
• iii) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 18.

The crystal form of a salt of a compound of formula (A) according to claim 71, wherein the crystal form of a salt of a compound of formula (A) is crystal form B of a hydrobromide of a compound of formula (A):

• which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including at least the characteristic peaks represented by the following °2θ:
• 4.1±0.2, 8.1±0.2, 15.0±0.2, 18.4±0.2, and 24.4±0.2;
• optionally, wherein the crystal form B further has one or more of the following definitions:
• i) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation further including the characteristic peaks represented by the following °2θ:
• 17.8±0.2, 20.3±0.2, 21.3±0.2, 22.0±0.2, and 22.8±0.2;
• or
• ii) which is characterized by an X-ray powder diffraction pattern obtained using CuKα radiation including the following characteristic peaks:
• Angle °2θ ± 0.2°2θ
• Relative intensity %
• 4.05
• 100.0
• 8.10
• 69.4
• 10.57
• 17.3
• 12.14
• 19.9
• 12.74
• 16.7
• 13.54
• 14.6
• 15.05
• 74.2
• 15.43
• 18.4
• 16.23
• 19.8
• 17.84
• 27.2
• 18.45
• 82.8
• 19.27
• 12.0
• 20.35
• 37.7
• 21.33
• 24.5
• 22.02
• 33.6
• 22.77
• 32.0
• 23.65
• 12.8
• 24.44
• 55.0
• 26.84
• 14.5
• 30.65
• 12.9;
• or
• iii) characterized in that it has an X-ray powder diffraction pattern substantially as shown in FIG. 19;
• and/or
• iv) characterized in that it has endothermic peaks at 101.6±2° C. and 113.3±2° C. in differential scanning calorimetry analysis;
• and/or
• v) characterized in that it has a weight loss of 4.59±0.5% at 90° C. in thermogravimetric analysis.