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US-20260125368-A1 - SALT OF GLP-1R AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF

US20260125368A1US 20260125368 A1US20260125368 A1US 20260125368A1US-20260125368-A1

Abstract

A salt form of compound I is a GLP-1R agonist, a preparation method therefor, and use thereof are provided. The salt has excellent GLP-1R agonistic activity and has good bioavailability in animals, thus being suitable for preparing a preparation for treating metabolic diseases, tumors, autoimmune diseases, or metastatic diseases.

Inventors

  • Long Zhang
  • Zhangming NIU
  • Yang Hu

Assignees

  • MINDRANK AI LTD.

Dates

Publication Date
20260507
Application Date
20230707
Priority Date
20220707

Claims (16)

  1. 1 . A pharmaceutically acceptable salt of a compound represented by formula (I), wherein R is selected from halogen and CN; the pharmaceutically acceptable salt refers to a pharmaceutically non-toxic acid addition salt or base addition salt; preferably, the acid addition salt is a salt formed by the compound represented by formula (I) with an inorganic or organic acid, including a hydrobromide, a hydrochloride, a sulfate, a bisulfate, a sulfite, a phosphate, a borate, an acetate, an oxalate, a valerate, a benzoate, a lactate, a toluate, a citrate, a malate, a maleate, a fumarate, a succinate, a tartrate, a methanesulfonate, a benzenesulfonate, and ap-toluenesulfonate; more preferably, the acid addition salt is a hydrochloride, an acetate, a citrate, a malate, a succinate, a tartrate, a fumarate, a maleate, or a methanesulfonate; particularly, the acid addition salt is a citrate or a maleate; preferably, the base addition salt is a salt formed by the compound represented by formula (I) with an inorganic or organic base, including salts formed with alkali metals, such as a sodium salt, a lithium salt, a potassium salt, a calcium salt, a magnesium salt, and the like, and amine salts, including salts formed with ammonia (NH 3 ), primary amines, secondary amines, or tertiary amines, such as a tetramethylamine salt, a tetraethylamine salt, a methylamine salt, a dimethylamine salt, a trimethylamine salt, a triethylamine salt, an ethylamine salt, a meglumine salt, a choline salt, and a tromethamine salt; more preferably, the base addition salt is a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a meglumine salt, a choline salt, or a tromethamine salt; particularly, the base addition salt is a sodium salt, a potassium salt, a magnesium salt, a meglumine salt, or a tromethamine salt; preferably, the compound represented by formula (I) is selected from the following compound I-1 and compound I-2: preferably, an acid addition salt of compound I-1 is a hydrochloride, a tartrate, a maleate, a methanesulfonate, or a citrate; an acid addition salt of compound I-2 is a citrate, a tartrate, a malate (e.g., an L-malate), a fumarate, a methanesulfonate, or a maleate; preferably, a base addition salt of compound I-1 is a sodium salt, a potassium salt, a meglumine salt, or a tromethamine salt; a base addition salt of compound I-2 is a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a meglumine salt, or a tromethamine salt.
  2. 2 . A crystal form A of the citrate of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 19.77±0.2°, 16.59±0.2°, 22.47±0.2°, and 20.20±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 16.59±0.2°, 19.77±0.2°, 22.47±0.2°, 20.20±0.2°, 24.84±0.2°, and 17.51±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the citrate has the diffraction angles (2θ) shown in Table 1, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 1 2θ (°) Intensity % 6.80 34.3 7.13 36.4 8.75 33.6 11.47 48.6 12.06 46.4 13.81 27.9 16.59 82.9 17.51 53.6 18.07 52.1 19.77 100.0 20.20 61.4 21.02 22.9 22.47 68.6 24.84 60.7 27.78 40.7 preferably, the crystal form A of the citrate has the X-ray powder diffraction intensities shown in Table 1; preferably, the crystal form A of the citrate has an X-ray powder diffraction pattern substantially as shown in FIG. 3 ; preferably, the crystal form A of the citrate has a DSC thermogram with endothermic peaks at temperatures of about 107.80° C. and 130.63° C.; preferably, the crystal form A of the citrate has a DSC thermogram substantially as shown in FIG. 4 ; preferably, the crystal form A of the citrate has a TGA curve substantially as shown in FIG. 5 .
  3. 3 . A crystal form A of the sodium salt of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 19.24±0.2°, 20.68±0.2°, 6.81±0.2°, and 14.43±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 19.24±0.2°, 20.68±0.2°, 6.81±0.2°, 14.43±0.2°, 14.98±0.2°, and 6.40±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the sodium salt has the diffraction angles (2θ) shown in Table 2, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 2 2θ (°) Intensity % 4.07 36.4 6.40 47.5 6.81 55.0 14.43 53.3 14.98 52.1 17.69 37.6 18.02 40.9 19.24 100.0 20.68 90.1 24.27 34.3 24.84 29.8 26.44 26.4 preferably, the crystal form A of the sodium salt has the X-ray powder diffraction intensities shown in Table 2; preferably, the crystal form A of the sodium salt has an X-ray powder diffraction pattern substantially as shown in FIG. 8 ; preferably, the crystal form A of the sodium salt has a DSC thermogram with endothermic peaks at temperatures of about 149.11° C. and 174.11° C.; preferably, the crystal form A of the sodium salt has a DSC thermogram substantially as shown in FIG. 9 ; preferably, the crystal form A of the sodium salt has a TGA curve substantially as shown in FIG. 10 .
  4. 4 . A crystal form A of the potassium salt of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 13.90±0.2°, 14.43±0.2°, 16.20±0.2°, and 11.67±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 13.90±0.2°, 14.43±0.2°, 16.20±0.2°, 11.67±0.2°, 20.99±0.2°, and 16.79±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the potassium salt has the diffraction angles (2θ) shown in Table 3, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 3 2θ (°) Intensity % 5.80 23.5 6.60 36.0 8.76 4.8 9.99 32.7 11.67 49.1 12.11 21.0 13.42 37.7 13.90 100.0 14.43 96.1 16.20 70.6 16.79 45.8 17.25 13.5 18.95 31.1 20.39 33.9 20.99 47.4 21.95 39.3 23.06 29.2 23.62 39.0 24.91 32.8 25.45 15.2 26.39 21.0 27.80 8.3 32.76 7.2 preferably, the crystal form A of the potassium salt has the X-ray powder diffraction intensities shown in Table 3; preferably, the crystal form A of the potassium salt has an X-ray powder diffraction pattern substantially as shown in FIG. 11 .
  5. 5 . A crystal form B of the potassium salt of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 5.92±0.2°, 14.10±0.2°, 17.62±0.2°, and 17.94±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 5.92±0.2°, 14.10±0.2°, 17.62±0.2°, 17.94±0.2°, 11.92±0.2°, and 7.01±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form B of the potassium salt has the diffraction angles (2θ) shown in Table 4, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 4 2θ (°) Intensity % 5.92 100.0 7.01 40.3 8.74 22.1 9.56 11.0 10.92 19.2 11.92 70.3 12.27 17.2 14.10 95.8 15.19 28.1 15.64 19.5 16.94 19.8 17.62 89.6 17.94 80.4 18.74 20.7 20.12 11.0 20.69 17.8 20.90 20.8 21.84 39.4 22.24 31.4 23.33 18.4 24.01 23.3 25.17 13.2 25.69 17.4 26.68 15.6 27.09 10.0 28.38 6.7 29.37 8.5 32.02 8.9 preferably, the crystal form B of the potassium salt has the X-ray powder diffraction intensities shown in Table 4; preferably, the crystal form B of the potassium salt has an X-ray powder diffraction pattern substantially as shown in FIG. 12 .
  6. 6 . A crystal form A of the meglumine salt of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 18.15±0.2°, 12.87±0.2°, 22.87±0.2°, and 24.66±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 18.15±0.2°, 12.87±0.2°, 22.87±0.2°, 24.66±0.2°, 23.21±0.2°, and 19.57±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the meglumine salt has the diffraction angles (2θ) shown in Table 5, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 5 2θ (°) Intensity % 5.221 28.9 7.57 9.0 9.42 16.1 10.23 10.0 10.71 20.6 11.84 21.6 12.87 68.1 15.48 16.0 17.26 15.5 18.15 100.0 19.57 43.7 21.39 21.9 22.87 55.0 23.21 44.4 24.66 49.5 25.77 13.4 preferably, the crystal form A of the meglumine salt has the X-ray powder diffraction intensities shown in Table 5; preferably, the crystal form A of the meglumine salt has an X-ray powder diffraction pattern substantially as shown in FIG. 13 ; preferably, the crystal form A of the meglumine salt has a DSC thermogram with an endothermic peak at a temperature of about 120.06° C.; preferably, the crystal form A of the meglumine salt has a DSC thermogram substantially as shown in FIG. 14 ; preferably, the crystal form A of the meglumine salt has a TGA curve substantially as shown in FIG. 15 .
  7. 7 . A crystal form A of the tromethamine salt of compound I-1 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 3.50±0.2°, 6.97±0.2°, 13.91±0.2°, and 22.19±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 3.50±0.2°, 6.97±0.2°, 13.91±0.2°, 22.19±0.2°, 31.61±0.2°, 18.11±0.2°, and 20.55±0.2°; preferably, the crystal form A of the tromethamine salt has the X-ray powder diffraction data shown in Table 6 below: TABLE 6 2θ (°) Intensity % 3.505 100.0 6.972 98.6 10.168 6.1 11.067 5.1 11.490 2.8 13.910 35.2 14.417 5.2 14.924 2.3 15.762 11.9 16.365 8.7 16.911 3.9 17.185 6.5 17.805 4.8 18.118 17.3 18.974 13.9 19.714 3.9 20.553 14.0 20.864 9.0 22.190 28.8 23.433 2.9 23.885 6.0 24.275 3.5 26.026 8.2 27.098 6.1 27.481 4.0 27.994 5.3 28.520 11.0 30.271 5.1 31.617 18.4 33.113 3.4 35.165 9.7 38.801 2.5 preferably, the crystal form A of the tromethamine salt as the X-ray powder diffraction intensities shown in Table 6; preferably, the crystal form A of the tromethamine salt has an X-ray powder diffraction pattern substantially as shown in FIG. 16 ; preferably, the crystal form A of the tromethamine salt has a DSC thermogram with endothermic peaks at temperatures of about 109.95° C. and 166.02° C.; preferably, the crystal form A of the tromethamine salt has a DSC thermogram substantially as shown in FIG. 17 ; preferably, the crystal form A of the tromethamine salt has a TGA curve substantially as shown in FIG. 18 ; preferably, the crystal form A of the tromethamine salt is a N-methylpyrrolidone solvate.
  8. 8 . A crystal form A of the maleate of compound I-2 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 5.43±0.2°, 9.89±0.2°, 12.76±0.2°, and 8.30±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 5.43±0.2°, 9.89±0.2°, 12.76±0.2°, 8.30±0.2°, 21.31±0.2°, and 14.24±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the maleate has the diffraction angles (2θ) shown in Table 7, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 7 2θ (°) Intensity % 5.43 100.0 8.30 19.9 9.15 5.6 9.89 23.8 10.94 11.9 12.76 22.0 14.24 16.0 14.84 5.3 16.22 6.2 16.98 10.0 17.43 10.9 18.42 5.1 19.16 11.9 19.62 10.5 20.08 4.5 21.31 19.3 22.09 9.8 24.87 10.0 25.32 5.5 25.77 8.1 28.08 5.4 28.40 4.1 preferably, the crystal form A of the maleate has the X-ray powder diffraction intensities shown in Table 7; preferably, the crystal form A of the maleate has an X-ray powder diffraction pattern substantially as shown in FIG. 24 ; preferably, the crystal form A of the maleate has a DSC thermogram with an endothermic peak at a temperature of about 119.30° C.; preferably, the crystal form A of the maleate has a DSC thermogram substantially as shown in FIG. 25 ; preferably, the crystal form A of the maleate has a TGA curve substantially as shown in FIG. 26 .
  9. 9 . A crystal form A of the potassium salt of compound I-2 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 11.51±0.2°, 15.42±0.2°, 20.20±0.2°, and 9.52±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 11.51±0.2°, 15.42±0.2°, 20.20±0.2°, 9.52±0.2°, 5.06±0.2°, and 25.38±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the potassium salt has the diffraction angles (2θ) shown in Table 8, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 8 2θ (°) Intensity % 5.06 14.2 7.67 11.2 9.52 15.5 11.51 100.0 13.86 4.0 15.42 59.8 17.41 6.1 19.14 3.1 20.20 25.1 21.45 4.8 25.38 12.0 preferably, the crystal form A of the maleate as the X-ray powder diffraction intensities shown in Table 8; preferably, the crystal form A of the potassium salt has an X-ray powder diffraction pattern substantially as shown in FIG. 28 ; preferably, the crystal form A of the potassium salt has a DSC thermogram with an endothermic peak at a temperature of about 118.44° C.; preferably, the crystal form A of the potassium salt has a DSC thermogram substantially as shown in FIG. 29 ; preferably, the crystal form A of the potassium salt has a TGA curve substantially as shown in FIG. 30 .
  10. 10 . A crystal form A of the magnesium salt of compound I-2 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 13.92±0.2°, 13.46±0.2°, 14.74±0.2°, and 20.43±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 13.92±0.2°, 13.46±0.2°, 14.74±0.2°, 20.43±0.2°, 20.16±0.2°, and 17.21±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the magnesium salt has the diffraction angles (2θ) shown in Table 9, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 9 2θ (°) Intensity % 4.55 9.6 6.65 4.5 7.14 4.7 7.87 4.2 9.83 5.5 11.04 5.7 11.63 6.0 12.97 7.6 13.46 54.8 13.92 100.0 14.74 28.7 15.37 5.9 15.84 17.8 16.10 10.5 17.21 23.0 18.76 8.7 20.16 23.7 20.43 26.3 20.92 11.3 22.29 6.3 22.63 5.9 24.21 4.5 25.26 11.1 25.89 6.6 preferably, the crystal form A of the magnesium salt has the X-ray powder diffraction intensities shown in Table 9; preferably, the crystal form A of the magnesium salt has an X-ray powder diffraction pattern substantially as shown in FIG. 32 .
  11. 11 . A crystal form A of the meglumine salt of compound I-2 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 3.05±0.2°, 9.38±0.2°, 17.62±0.2°, and 12.01±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 3.05±0.2°, 9.38±0.2°, 17.62±0.2°, 12.01±0.2°, 20.39±0.2°, and 14.88±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the meglumine salt has the diffraction angles (2θ) shown in Table 10, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 10 2θ (°) Intensity % 3.05 100.0 9.38 79.6 12.01 21.6 12.50 8.6 14.88 15.0 16.18 12.4 17.62 23.5 19.53 5.0 20.39 21.0 21.71 3.7 22.67 4.1 23.35 6.3 24.41 2.6 26.49 2.8 27.56 2.8 30.15 3.0 preferably, the crystal form A of the meglumine salt has the X-ray powder diffraction intensities shown in Table 10; preferably, the crystal form A of the meglumine salt has an X-ray powder diffraction pattern substantially as shown in FIG. 33 ; preferably, the crystal form A of the meglumine salt has a DSC thermogram with an endothermic peak at a temperature of about 123.07° C.; preferably, the crystal form A of the meglumine salt has a DSC thermogram substantially as shown in FIG. 34 ; preferably, the crystal form A of the meglumine salt has a TGA curve substantially as shown in FIG. 35 .
  12. 12 . A crystal form A of the tromethamine salt of compound I-2 as claimed in claim 1 , wherein an X-ray powder diffraction (XRPD) pattern of the crystal form comprises four or more peaks at diffraction angles (2θ) of 3.68±0.2°, 7.48±0.2°, 17.21±0.2°, and 19.15±0.2°; preferably, the X-ray powder diffraction (XRPD) pattern of the crystal form comprises peaks at diffraction angles (2θ) of 3.68±0.2°, 7.48±0.2°, 17.21±0.2°, 19.15±0.2°, 16.73±0.2°, and 15.74±0.2°; preferably, the X-ray powder diffraction pattern of the crystal form A of the tromethamine salt has the diffraction angles (2θ) shown in Table 11, wherein the 2θ angles have a margin of error of ±0.20°: TABLE 11 2θ (°) Intensity % 3.68 100.0 7.48 51.3 14.82 7.2 15.74 9.0 16.73 9.2 17.21 12.7 19.15 9.6 20.18 3.3 21.95 3.9 22.67 4.9 24.66 4.0 27.68 4.3 preferably, the crystal form A of the tromethamine salt has the X-ray powder diffraction intensities shown in Table 11; preferably, the crystal form A of the tromethamine salt has an X-ray powder diffraction pattern substantially as shown in FIG. 36 ; preferably, the crystal form A of the tromethamine salt has a DSC thermogram with an endothermic peak at a temperature of about 167.96° C.; preferably, the crystal form A of the tromethamine salt has a DSC thermogram substantially as shown in FIG. 37 ; preferably, the crystal form A of the tromethamine salt has a TGA curve substantially as shown in FIG. 38 .
  13. 13 . A preparation method for the pharmaceutically acceptable salt of compound I-1 or compound I-2 as claimed in claim 1 , comprising reacting compound I-1 or compound I-2 with an acid or base in a solvent to give the pharmaceutically acceptable salt of compound I-1 or compound I-2, wherein: preferably, the acid is selected from an inorganic acid and an organic acid, wherein the inorganic acid may be selected from hydrobromic acid, hydrochloric acid, sulfuric acid, sulfurous acid, phosphoric acid, and boric acid; the organic acid may be selected from acetic acid, oxalic acid, valeric acid, benzoic acid, lactic acid, toluic acid, citric acid, malic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; preferably, the base is selected from an inorganic base and an organic base, wherein the inorganic base may be selected from alkali metal hydroxides and alkaline earth metal hydroxides, such as sodium hydroxide, lithium hydroxide, potassium hydroxide, calcium hydroxide, and magnesium hydroxide; the organic base may be selected from ammonia, primary amines, secondary amines, and tertiary amines, such as tetramethylamine, tetraethylamine, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, meglumine, choline, and tromethamine; preferably, a molar ratio of compound I-1 or I-2 to the acid or the base may be 1:0.8-1:2; preferably, the molar ratio is 1:0.9-1:1.8.
  14. 14 . The preparation method as claimed in claim 13 , wherein the preparation method for the pharmaceutically acceptable salt of compound I-1 comprises the following methods 1a-1e: method 1a, comprising: dissolving compound I-1 in acetonitrile, adding concentrated hydrochloric acid, L-tartaric acid, maleic acid, or methanesulfonic acid, stirring at room temperature, then filtering, and drying to give the hydrochloride of compound I-1, the tartrate of compound I-1, the maleate of compound I-1, or the methanesulfonate of compound I-1; method 1b, comprising: dissolving compound I-1 and citric acid in acetone, stirring at room temperature, then filtering, and drying to give the citrate of compound I-1; method 1c, comprising: dissolving compound I-1 and sodium hydroxide or potassium hydroxide in acetonitrile or methyl isobutyl ketone, stirring at room temperature, then filtering, and drying to give the sodium salt of compound I-1 or the potassium salt of compound I-1; method 1d, comprising: dissolving compound I-1 and meglumine in acetonitrile, stirring at room temperature, then filtering, and drying to give the meglumine salt of compound I-1; and method 1e, comprising: dissolving compound I-1 and tromethamine in N-methylpyrrolidone, adding to toluene, stirring at room temperature, then filtering, and drying to give the tromethamine salt of compound I-1, wherein preferably, a volume ratio of N-methylpyrrolidone to toluene is 2:15; the preparation method for the pharmaceutically acceptable salt of compound I-2 comprises the following methods 2a-2f: method 2a, comprising: dissolving compound I-2 and citric acid or L-tartaric acid in acetone, stirring at room temperature, then filtering, and drying to give the citrate of compound I-2 or the tartrate of compound I-2; method 2b, comprising: dissolving compound I-2 and L-malic acid or fumaric acid in acetonitrile/water, stirring at room temperature, then filtering, and drying to give the malate of compound I-2 or the fumarate of compound I-2, wherein preferably, a volume ratio of acetonitrile to water is 1:1; method 2c, comprising: dissolving compound I-2 and methanesulfonic acid or maleic acid in ethyl acetate, stirring at room temperature, then filtering, and drying to give the methanesulfonate of compound I-2 or the maleate of compound I-2; method 2d, comprising: dissolving compound I-2 and sodium hydroxide, potassium hydroxide, calcium hydroxide, or magnesium hydroxide in a mixed solvent of acetonitrile and water or in ethyl acetate, stirring at room temperature, then filtering, and drying to give the sodium salt of compound I-2, the potassium salt of compound I-2, the calcium salt of compound I-2, and the magnesium salt of compound I-2, wherein preferably, a volume ratio of acetonitrile to water is 1:1; method 2e, comprising: dissolving compound I-2 and meglumine in acetone, stirring at room temperature, then filtering, and drying to give the meglumine salt of compound I-2; and method 2f, comprising: dissolving compound I-2 and tromethamine in isopropanol, stirring at room temperature, then filtering, and drying to give the tromethamine salt of compound I-2.
  15. 15 . A pharmaceutical composition, comprising pharmaceutically acceptable salt of the compound represented by formula (I) as claimed in claim 1 and a pharmaceutically acceptable carrier.
  16. 16 . A method for treating a metabolic disease, a tumor, an autoimmune disease, or a metastatic disease, comprising administering a therapeutically effective amount of the pharmaceutically acceptable salt of the compound represented by formula (I) as claimed in claim 1 to a subject in need thereof, wherein: preferably, the disease is selected from T1D, T2DM, prediabetes, idiopathic T1D, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, glucose intolerance, diabetic neuropathy, diabetic nephropathy, kidney disease, diabetic retinopathy, adipocyte dysfunction, visceral adipocyte accumulation, sleep apnea, obesity, eating disorders, weight gain caused by use of other medicaments, excessive sugar craving, dyslipidemia, hyperinsulinemia, NAFLD, NAS, fibrosis, cirrhosis, hepatocellular carcinoma, cardiovascular disease, atherosclerosis, coronary artery disease, peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, congestive heart failure, myocardial infarction, stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, postprandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, Parkinson's disease, left ventricular hypertrophy, peripheral arterial disease, macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome XI, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, impaired fasting blood glucose conditions, hyperuricemia, gout, erectile dysfunction, skin and connective tissue abnormalities, psoriasis, foot ulcers, ulcerative colitis, hyperapoB lipoproteinemia, Alzheimer's disease, schizophrenia, impaired cognitive function, inflammatory bowel disease, short bowel syndrome, Crohn's disease, colitis, irritable bowel syndrome, polycystic ovary syndrome, and addiction.

Description

The present disclosure claims priority to a prior application filed with China National Intellectual Property Administration on Jul. 7, 2022, having the patent application number 202210804212X, and entitled “SALT OF GLP-1R AGONIST, PREPARATION METHOD THEREFOR AND USE THEREOF”, which is incorporated herein by reference in its entirety. TECHNICAL FIELD The present disclosure pertains to the field of drug development and particularly relates to a salt of a GLP-1R agonist, a preparation method therefor, and use thereof. BACKGROUND Diabetes is a chronic disease characterized by high blood glucose levels and is caused by (relatively or absolutely) insufficient insulin secretion or insulin action disorders. According to the ninth edition (the latest edition) of the International Diabetes Federation (IDF) Diabetes Atlas, approximately 463 million adults (aged 20-79) worldwide were living with diabetes in 2019, and the number of patients with diabetes is projected to be 578 million by 2030. At this rate, 700 million people worldwide will be living with diabetes in 2045. Therefore, diabetes has become one of the most pressing global social health problems of the 21st century. Currently, various pharmacological methods are available to treat hyperglycemia and the attendant T2DM (Hampp et al., Use of Antidiabetic Drugs in the U.S., 2003-2012, Diabetes Care, 37:1367-1374, 2014). These methods can be classified into six major categories, each acting through a different major mechanism. Insulin secretagogues, including sulfonylureas, dipeptidyl peptidase IV (PP-IV) inhibitors, and glucagon-like peptide-1 receptor (GLP-1R) agonists, enhance insulin secretion by acting on pancreatic β cells. Sulfonylureas have limited efficacy and tolerability, cause weight gain, and often induce hypoglycemia. DP-IV inhibitors have limited efficacy. Commercially available GLP-1R agonists are peptides that are administered by subcutaneous injection. Liraglutide is additionally approved for the treatment of obesity. Biguanides, such as metformin, are believed to act mainly by reducing hepatic glucose production. Biguanides often cause gastrointestinal discomfort and lactic acidosis, which further limit their use. α-Glucosidase inhibitors, such as acarbose, can reduce intestinal glucose absorption. These medicaments often cause gastrointestinal discomfort. Thiazolidinediones, such as pioglitazone and rosiglitazone, act on specific receptors in the liver, muscle, and adipose tissue. They regulate lipid metabolism and subsequently enhance the responses of these tissues to insulin action. Frequent use of these drugs may cause weight gain and may induce edema and anemia. Insulin, either alone or in combination with the medicaments described above, is used for more severe cases, and frequent use of insulin may also cause weight gain and involves a risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin, inhibit glucose reabsorption in the kidneys, thereby lowering blood glucose levels. This emerging drug may be associated with ketoacidosis and urinary tract infections. However, except for GLP-1R agonists and SGLT2 inhibitors, these drugs have limited efficacy and fail to address the most important issues: the functional decline of β cells and related obesity. Therefore, there is a need for more effective pharmaceuticals with relatively few side effects and easy administration. GLP-1 is a 30-amino-acid-long incretin hormone secreted by intestinal L cells in response to food intake. GLP-1 has been shown to stimulate insulin secretion in a physiological and glucose-dependent manner, reduce glucagon secretion, inhibit gastric emptying, reduce appetite, and stimulate β cell proliferation. In non-clinical trials, GLP-1 promotes continued β cell competence by stimulating transcription of genes important for glucose-dependent insulin secretion and by promoting β cell neogenesis (Meier, et al., Biodrugs, 17(2):93-102, 2013). In healthy individuals, GLP-1 plays an important role in regulating postprandial blood glucose levels by stimulating glucose-dependent insulin secretion by the pancreas to increase peripheral glucose absorption. GLP-1 also inhibits glucagon secretion, resulting in reduced hepatic glucose output. In addition, GLP-1 delays gastric emptying and slows small bowel movements to delay food absorption. In people with T2DM, the normal postprandial rise in GLP-1 is absent or reduced (Vilsboll et al., diabetes, 50: 609-613, 2001). The structure of GLP-1 has been correspondingly engineered and modified in scientific research to increase its half-life and thus prolong its in vivo biological effect. However, currently, clinically used long-acting GLP-1 analogs, such as liraglutide, exenatide, etc., are all polypeptides and require frequent injections, which lead to relatively poor patient compliance. Therefore, the development of small-molecule GLP-1R agonists wil