Polymorphs of phenylpyrrole aminoguanidine salts and phenylpyrrole aminoguanidinium salts

Abstract

The present disclosure relates to highly soluble crystalline forms of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts. The present disclosure also relates to the use of said crystalline forms in medicine.

Description

[Technical field]

[0001] The present invention relates to salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine that have high solubility at low pH. [Background technology]

[0002] The melanocortin system is a collection of neuropeptidergic and immunoendocrine signaling pathways that play essential roles in the homeostatic regulation of diverse physiological functions, including melanogenesis, stress response, inflammation, immunoregulation, and adrenal cortical steroidogenesis. The system is composed of multiple components, including five G protein-coupled melanocortin receptors: melanocortin receptor 1 (MC1R) to MC5R; peptide ligands; α, β, γ-melanocyte-stimulating hormone (α, β, γ-MSH); adrenocorticotropic hormone (ACTH) secreted by the anterior pituitary gland; and endogenous antagonists. The biological functions of the melanocortin system are mediated by five melanocortin receptors (MCRs), which have distinct tissue distributions, differential signal transduction, and various biological activities in different organ systems.

[0003] Phenylpyrrole aminoguanidine derivatives with activity against melanocortin receptors have been previously disclosed. One such compound was first shown to bind MC1R and then not cause canonical cAMP production (and thus no MC1R-induced melanin production), but instead inhibited ERK1 / 2 phosphorylation and Ca2+ + The anti-inflammatory AP1189 (N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine) was identified as a biased dual agonist at the MC1R and MC3R receptors that appears to induce an alternative pathway involving recruitment of Summary of the Invention

[0004] The present inventors have discovered salts of AP1189 that have particularly favorable solubility profiles for gastric delivery. The present inventors have found that certain polymorphs of AP1189 salts have very high solubility, especially at low pH.

[0005] Thus, one aspect of the present disclosure is Cu K at 11.5±0.2, 23.5±0.2, and 27.0±0.2. α Crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactivity.

[0006] Another aspect of the present disclosure is Cu K at 9.7±0.2, 22.8±0.2, and 26.7±0.2. α Crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactivity.

[0007] The present disclosure also provides methods for preparing such crystalline forms.

[0008] One aspect of the present disclosure provides a method for preparing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate in crystalline form A as disclosed herein, said method comprising: mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine and acetic acid in a solvent to form a mixture; ii. isolating crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate from said mixture.

[0009] One aspect of the present disclosure provides a method for preparing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate in crystalline form A as disclosed herein, said method comprising: mixing a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium and acetic acid in a solvent to form a mixture; ii. isolating crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate from the mixture.

[0010] One aspect of the present disclosure provides a method for preparing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate in crystalline form A as disclosed herein, said method comprising: mixing iN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate in a solvent to form a composition; ii. isolating crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate from said composition.

[0011] One aspect of the present disclosure provides a method for preparing crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate as disclosed herein, said method comprising: mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine and succinic acid in a solvent to form a mixture; ii. isolating crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate from the mixture.

[0012] One aspect of the present disclosure provides a method for preparing crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate as disclosed herein, said method comprising: mixing a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium and succinic acid in a solvent to form a mixture; ii. isolating crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate from the mixture.

[0013] One aspect of the present disclosure provides crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate produced by the methods disclosed herein.

[0014] One aspect of the present disclosure provides crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate produced by the methods disclosed herein.

[0015] One aspect of the present disclosure provides a pharmaceutical composition comprising crystalline Form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate as disclosed herein and a pharma- ceutically acceptable excipient.

[0016] One aspect of the present disclosure provides a pharmaceutical composition comprising crystalline Form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate as disclosed herein and a pharma- ceutically acceptable excipient.

[0017] One aspect of the present disclosure provides a method of preparing a pharmaceutical composition comprising mixing crystalline Form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate as disclosed herein and a pharma- ceutically acceptable excipient.

[0018] One aspect of the present disclosure provides a method of preparing a pharmaceutical composition, the method comprising mixing crystalline Form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate disclosed herein and a pharma- ceutically acceptable excipient.

[0019] One aspect of the disclosure provides a method of treating a disease or disorder in a subject in need thereof, the method comprising administering to a subject in need thereof crystalline Form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate disclosed herein, crystalline Form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene guanidinium succinate disclosed herein, or a pharmaceutical composition disclosed herein.

[0020] One aspect of the present disclosure provides use of crystalline Form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate as disclosed herein, or crystalline Form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate as disclosed herein, or a pharmaceutical composition as disclosed herein, for the manufacture of a medicament for the treatment of a disease or disorder.

[0021] One aspect of the present disclosure is to provide a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt that has high solubility at low pH, for example at pH 1.2. Thus, one aspect is i. Cu K at 13.0±0.2, 15.1±0.2 and 19.9±0.2 α Crystalline form XIV of AP1189 besylate, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; ii. Cu K at 16.8±0.2, 23.4±0.2 and 23.6±0.2 α Crystalline form XIX of AP1189 oxoglutarate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; iii. Cu K at 14.8±0.2, 24.2±0.2 and 25.5±0.2 α Crystalline form XX of AP1189 DL-mandelic acid, which exhibits at least an X-ray line (2 theta value) in the powder diffraction pattern when measured using radioactive material; iv. Cu K at 20.1±0.2, 24.1±0.2 and 24.5±0.2 α AP1189 hippuric acid crystalline form XXII, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; Cu K at v. 13.3±0.2, 15.1±0.2 and 25.6±0.2 α Crystalline form XXIII of AP1189 formate, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; vi. Cu K at 3.8±0.2, 9.9±0.2 and 11.9±0.2 α Crystalline form XXIV of AP1189L-lactic acid, which exhibits at least an X-ray line (2-theta value) in the powder diffraction pattern when measured using radioactive material; vii. Cu K at 9.8±0.2, 11.9±0.2 and 27.6±0.2 α Crystalline form XXV of AP1189DL-lactic acid, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; viii. Cu K at 8.3±0.2, 15.9±0.2 and 21.9±0.2 αCrystalline form XXVI of AP1189 glutaric acid, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive materials, and ix. Cu K at 13.4±0.2, 14.5±0.2 and 25.5±0.2 α The present invention provides a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt selected from the group consisting of crystalline form XXIX of AP1189 adipic acid, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactivity.

[0022] One aspect of the present disclosure is to provide a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt that can be converted into a useful crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt. Thus, one aspect of the present disclosure is to provide a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt that can be converted into a useful crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt. i. Cu K at 13.4±0.2, 22.2±0.2 and 26.8±0.2 α Crystalline form III of AP1189 napadisylate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; ii. Cu K at 5.4±0.2, 15.6±0.2 and 23.4±0.2 α Crystalline form IV of AP1189 napadisylate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; iii. Cu K at 14.5±0.2, 16.5±0.2 and 18.6±0.2 α Crystalline form V of AP1189 esylate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; iv. Cu K at 4.8±0.2, 12.8±0.2 and 16.5±0.2 α Crystalline form VI of AP1189 edisylate salt, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; Cu K at v. 6.1 ± 0.2, 15.7 ± 0.2 and 23.6 ± 0.2 α Crystalline form VII of AP1189 edisylate, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; vi. Cu K at 15.5±0.2, 20.7±0.2 and 21.7±0.2 α Crystalline form VIII of AP1189 edisylate salt, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; vii. Cu K at 4.5±0.2, 16.7±0.2 and 24.7±0.2 α Crystalline form IX of AP1189 edisylate salt, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; viii. Cu K at 15.3±0.2, 21.4±0.2 and 25.1±0.2 α Crystalline form X of AP1189 nitrate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactivity; Cu K at ix.7.0±0.2, 13.8±0.2 and 15.7±0.2 α Crystalline form XI of AP1189 cyclamate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; Cu K at x.7.3±0.2, 15.3±0.2 and 17.9±0.2 α Crystalline form XII of AP1189 cyclamate, which exhibits at least an X-ray line (2-theta value) in its powder diffraction pattern when measured using radioactive material; xi. Cu K at 15.3±0.2, 18.5±0.2 and 18.7±0.2 α Crystalline form XIII of AP1189 cyclamate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; xii. Cu K at 19.5±0.2, 23.3±0.2 and 25.8±0.2 αCrystalline form XV of AP1189 oxalate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material; xiii. Cu K at 17.1±0.2, 17.9±0.2 and 19.6±0.2 α Crystalline form XVI of AP1189 oxalate, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; xiv. Cu K at 6.3±0.2, 10.6±0.2 and 19.8±0.2 α Crystalline form XVII of AP1189 oxalate, which exhibits at least an X-ray line (2 theta value) in a powder diffraction pattern when measured using radioactive material; Cu K at xv.6.5±0.2, 11.5±0.2 and 14.8±0.2 α Crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits at least an X-ray line (2-theta value) in the powder diffraction pattern when measured using radioactive material; xvi. Cu K at 5.4±0.2, 10.0±0.2 and 24.6±0.2 α Crystalline form XXI of AP1189DL-Mandelic acid, which exhibits at least an X-ray line (2-theta value) in the powder diffraction pattern when measured using radioactive material; xvii. Cu K selected from the group consisting of 16.9±0.2, 25.6±0.2, 27.1±0.2, 28.2±0.2 and 28.7±0.2 α AP1189 glutaric acid crystalline form XXVII, which further exhibits one or more X-ray lines (2 theta values) in a powder diffraction pattern when measured using radioactive materials; and xviii. Cu K at 14.2±0.2, 16.9±0.2 and 24.5±0.2 α The present invention provides a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt selected from the group consisting of crystalline form XXVIII of AP1189 glutaric acid, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactivity.

[0023] One aspect of the present disclosure is to provide N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts that can be converted into useful crystalline forms of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts. Thus, one aspect of the present disclosure is to provide iN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate, ii. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate; iii. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium fumarate; iv. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium napadisilate, vN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium esylate, vi. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium edisylate, vii. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium nitrate; viii. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium cyclamate; ix. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium besylate, xN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium oxalate, xi. Salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine(+)-camphor-10-sulfonic acid; xii. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium oxoglutarate; xiii. Salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine DL-mandelic acid; xiv. Salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine hippuric acid, xv. N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium fumarate, xvi. Salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine L-lactic acid; xvii. Salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine DL-lactic acid; xviii. Salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine glutaric acid, and xix. A compound selected from the group consisting of salts of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine adipic acid is provided.

[0024] One aspect of the present disclosure provides a composition, pharmaceutical composition, liquid composition, unit dosage form or oral formulation comprising a crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt disclosed herein.

[0025] One aspect of the disclosure provides the use of such crystalline forms, compositions, pharmaceutical compositions, liquid compositions, unit dosage forms or pharmaceutical formulations of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts in medicine.

[0026] One aspect of the present disclosure provides the use of such crystalline forms, compositions, pharmaceutical compositions, liquid compositions, unit dosage forms or oral formulations of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts in the treatment of renal disease, arthritic disease, cardiovascular disease, atherosclerosis, viral disease or disorder, or systemic inflammatory disease. [Brief description of the drawings]

[0027] [Figure 1] FIG. 1 shows the XRPD diffractogram for pattern 1 of AP1189 acetate crystallized from acetonitrile. [Diagram 2] FIG. 1 shows the XRPD diffractogram for pattern 1 of AP1189 acetate crystallized from ethyl acetate. [Diagram 3] FIG. 1 shows the XRPD diffractogram for pattern 3 of AP1189 acetate crystallized from THF. [Figure 4] FIG. 1 shows the XRPD diffractogram for pattern 1 of AP1189 tosylate crystallized from methanol. [Diagram 5] FIG. 1 shows the XRPD diffractogram for pattern 1 of AP1189 fumarate salt crystallized from isopropyl alcohol:water 90:10 v / v. [Figure 6] FIG. 1 shows the XRPD diffractogram for pattern 1 of AP1189 succinate crystallized from isopropyl alcohol:water 90:10 v / v. [Figure 7] Figure 1 shows the TGA / DSC thermogram of pattern 1 of AP1189 acetate from 1,4-dioxane. Peak temperature: 183.75°C; Onset: 164.62°C; Enthalpy (normalized): 629.95 J / g. Weight loss: 0.001 mg; Weight loss percentage: 0.057%. [Figure 8] Figure 1 shows the DSC thermogram of pattern 1 of AP1189 acetate from acetonitrile. Peak temperature 197.86°C; Onset: 192.19°C; Enthalpy (normalized): 147.26 J / g. [Figure 9]Figure 1 shows TGA / DSC thermograms of patterns 1 and 2 of AP1189 acetate from 2-methylTHF. Peak temperature: 194.18°C; Onset: 171.54°C; Enthalpy (normalized): 475.77 J / g. Weight loss: 0.021 mg; Weight loss percentage: 0.478%. [Figure 10] 1 shows the TGA / DSC thermogram of pattern 3 of AP1189 acetate from THF. Peak temperature: 118.76° C.; Onset: 100.62° C.; Enthalpy (normalized): 138.49 J / g. First weight loss section: Weight loss: 0.002 mg; Weight loss percentage: 0.067%. Second weight loss section: Weight loss: 0.672 mg; Weight loss percentage: 18.610%. [Figure 11] Figure 1 shows the TGA / DSC thermogram of pattern 1 of AP1189 tosylate salt from IPA:water 90:10 v / v after storage at 40°C. Peak temperature: 239.24°C; Onset: 233.75°C; Enthalpy (normalized): 99.785 J / g. Weight loss: 0.006 mg; Weight loss percentage: 0.330%. [Figure 12] Figure 1 shows the TGA / DSC thermogram of pattern 1 of AP1189 fumaric acid from 2-propanol:water 90:10. Peak temperature: 218.27°C; Onset: 214.61°C; Enthalpy (normalized): 68.467 J / g. WE 0.012 mg; Weight loss: 0.319%. [Figure 13] Figure 1 shows the DSC thermogram of Pattern 1 for AP1189 succinate salt from IPA:water 90:10 v / v. Peak temperature: 196.27°C; Onset: 195.18°C; Enthalpy (normalized): 196.27 J / g. [Figure 14] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 napadisylate. [Figure 15] FIG. 2 shows the XRPD diffractogram of AP1189 napadisylate pattern 2. [Figure 16] FIG. 1 shows the XRPD diffractogram of AP1189 esylate pattern 1. [Figure 17] FIG. 1 shows the XRPD diffractogram of AP1189 edisylate pattern 1. [Figure 18]FIG. 2 shows the XRPD diffractogram of AP1189 edisylate pattern 2. [Figure 19] FIG. 1 shows the XRPD diffractogram of AP1189 edisylate salt pattern 4. [Figure 20] FIG. 1 shows the XRPD diffractogram of AP1189 edisylate salt pattern 5. [Figure 21] 1 shows the XRPD diffractogram of pattern 1 of AP1189 nitrate. [Figure 22] FIG. 2 shows the XRPD diffractogram of AP1189 cyclamate pattern 2. [Figure 23] 1 shows the XRPD diffractogram of pattern 4 of AP1189 cyclamate. [Figure 24] FIG. 1 shows the XRPD diffractogram of pattern 5 of AP1189 cyclamate. [Diagram 25] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 besylate. [Figure 26] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 oxalate. [Figure 27] FIG. 2 shows the XRPD diffractogram of pattern 2 of AP1189 oxalate. [Figure 28] FIG. 1 shows the XRPD diffractogram of pattern 4 of AP1189 oxalate. [Figure 29] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 (+)-camphor-10-sulfonic acid. [Diagram 30] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 oxoglutarate. [Diagram 31] FIG. 1 shows the XRPD diffractogram of pattern 2 of AP1189DL-Mandelic acid. [Diagram 32] FIG. 1 shows the XRPD diffractogram of pattern 3 of AP1189DL-Mandelic acid. [Diagram 33] 1 shows the XRPD diffractogram of pattern 1 of AP1189 hippuric acid. [Diagram 34] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 formic acid. [Diagram 35] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 L-lactic acid. [Diagram 36] 1 shows the XRPD diffractogram of pattern 1 of AP1189DL-lactic acid. [Figure 37] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 glutaric acid. [Figure 38] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 glutaric acid. [Figure 39] FIG. 1 shows the XRPD diffractogram of pattern 1 of AP1189 adipic acid. [Diagram 40] TG / DSC thermogram of AP1189 napadisylate pattern 1. Weight loss: 0.1356 mg. Weight loss percentage: 3.974%. Enthalpy (normalized): 29.422 J / g; Onset x: 87.38° C.; Peak temperature: 104.76° C. Enthalpy (normalized): 1.8937 J / g; Peak temperature: 187.47° C. [Diagram 41] TG / DSC thermogram of AP1189 esylate salt pattern 1. Weight loss: 0.032 mg. Weight loss percentage: 0.911%. Enthalpy (normalized): 42.119 J / g; Onset x: 201.95° C.; Peak temperature: 207.06° C. [Diagram 42] TG / DSC thermogram of AP1189 edisylate salt pattern 2. Weight loss: 0.061 mg. Weight loss percentage: 1.175%. Weight loss: 0.158 mg. Weight loss percentage: 3.040%. Enthalpy (normalized): 3.1886 J / g; Onset x: 220.71° C.; Peak temperature: 224.57° C. [Diagram 43] TG / DSC thermogram of AP1189 edisylate salt pattern 4. Weight loss: 1.463 mg. Weight loss percentage: 6.372%. Enthalpy (normalized): 100.17 J / g. Onset x: 208.40° C.; Peak temperature: 217.37° C. [Diagram 44] TG / DSC thermogram of AP1189 edisylate salt pattern 5. Weight loss: 0.120 mg. Weight loss percentage: 4.701%. Enthalpy (normalized): 54.800 J / g; onset x: 58.52° C.; peak temperature: 78.51° C. Enthalpy (normalized): 0.93567 J / g; onset x not found; peak temperature: 151.11° C. [Diagram 45] TG / DSC thermogram of Pattern 1 of AP1189 Nitrate. Weight Loss: 0.095 mg. Weight Loss Percentage: 2.139%. Enthalpy (normalized): 0.4851 J / g; Onset x: 178.54°C; Peak temperature: 182.88°C. [Figure 46] TG / DSC thermogram of AP1189 cyclamate pattern 2. Weight loss: 0.033 mg. Weight loss percentage: 0.459%. Enthalpy (normalized): 6.4491 J / g; Onset x: 129.90° C.; Peak temperature: 137.27° C. [Figure 47] TG / DSC thermogram of AP1189 cyclamate pattern 4. Weight loss: 0.041 mg. Weight loss percentage: 1.080%. Weight loss: 0.088 mg. Weight loss percentage: 2.337%. Enthalpy (normalized): 0.0143 J / g; Onset x: 133.07° C.; Peak temperature: 138.20° C. [Figure 48] TG / DSC thermogram of AP1189 besylate pattern 1. Weight loss: 0.014 mg. Weight loss percentage: 2.369%. Enthalpy (normalized): 48.524 J / g; Onset x: 216.45° C.; Peak temperature: 220.49° C. [Figure 49] TG / DSC thermogram of AP1189 oxalate pattern 1. Weight loss: 0.023 mg. Weight loss rate: 1.665%. Enthalpy (normalized): 0.32686 J / g; Peak temperature: 210.52° C. [Figure 50] TG / DSC thermogram of AP1189 oxalate pattern 2. Weight loss: 0.035 mg. Weight loss percentage: 2.156%. Enthalpy (normalized): 40.935 J / g; Onset x: 207.42° C.; Peak temperature: 211.50° C. [Figure 51] TG / DSC thermogram of pattern 4 of AP1189 oxalate. Weight loss: 0.016 mg. Weight loss rate: 2.164%. [Figure 52]TG / DSC thermogram of pattern 1 of AP1189(+)-camphor-10-sulfonic acid. Weight loss: 0.017 mg. Weight loss percentage: 1.843%. Enthalpy (normalized): 107.65 J / g; Onset x: 205.38° C.; Peak temperature: 209.93° C. [Diagram 53] TG / DSC thermogram of AP1189 oxoglutarate pattern 1. Weight loss: 0.167 mg. Weight loss rate: 2.379% Weight loss: 0.462 mg Weight loss rate: 6.588% Enthalpy (normalized): 68.335 J / g Onset x: 81.31°C Peak temperature: 87.92°C [Figure 54] TG / DSC thermogram of AP1189DL-Mandelic acid pattern 2. Weight loss: 0.424 mg. Weight loss percentage: 8.372%. Enthalpy (normalized): 43.266 J / g; Onset x: 104.13° C.; Peak temperature: 110.06° C. [Figure 55] TG / DSC thermogram of AP1189DL-Mandelic acid pattern 3. Weight loss: 0.066mg. Weight loss rate: 3.021% Weight loss: 0.081mg Weight loss rate: 3.698%. [Figure 56] TG / DSC thermogram of AP1189 Hippuric Acid Pattern 1. Weight Loss: 0.022 mg. Weight Loss Percentage: 1.294%. Weight Loss: 0.026 mg. Weight Loss Percentage: 1.495% Enthalpy (normalized): 4.7263 J / g; Onset x: 138.92° C.; Peak temperature: 149.72° C. [Figure 57] FT-IR spectrum of AP1189 napadisylate pattern 1. [Figure 58] FT-IR spectrum of AP1189 napadisylate pattern 2. [Figure 59] FT-IR spectrum of AP1189 esylate pattern 1. [Figure 60] FT-IR spectrum of AP1189 edisylate pattern 2. [Figure 61] FT-IR spectrum of AP1189 edisylate salt pattern 4. [Figure 62]FT-IR spectrum of AP1189 edisylate salt pattern 5. [Figure 63] FT-IR spectrum of AP1189 nitrate pattern 1. [Figure 64] FT-IR spectrum of AP1189 cyclamate pattern 2. [Figure 65] FT-IR spectrum of AP1189 cyclamate pattern 4. [Figure 66] FT-IR spectrum of AP1189 edisylate salt pattern 4. [Figure 67] FT-IR spectrum of AP1189 besylate pattern 1. [Figure 68] FT-IR spectrum of AP1189 oxalate pattern 1. [Figure 69] FT-IR spectrum of AP1189 oxalate pattern 2. [Figure 70] FT-IR spectrum of AP1189 oxalate pattern 4. [Figure 71] FT-IR spectrum of AP1189 (+)-camphor-10-sulfonic acid pattern 1. [Figure 72] FT-IR spectrum of oxoglutarate pattern 1. [Figure 73] FT-IR spectrum of AP1189DL-mandelic acid pattern 2. [Figure 74] FT-IR spectrum of AP1189DL-mandelic acid pattern 3. [Figure 75] FT-IR spectrum of AP1189 hippuric acid pattern 1. [Figure 76] FT-IR spectrum of AP1189 formic acid pattern 1. [Figure 77] FT-IR spectrum of AP1189 L-lactate pattern 1. [Figure 78] FT-IR spectrum of AP1189DL-lactate pattern 1 [Figure 79]FT-IR spectrum of AP1189 glutaric acid pattern 1. [Figure 80] FT-IR spectrum of AP1189 glutaric acid pattern 2. [Figure 81] TG / DSC thermogram of AP1189 napadisylate pattern 2. Weight loss: 0.157mg. Weight loss rate: 7.940%. [Figure 82] TG / DSC thermogram of AP1189 edisylate salt pattern 1. Weight loss: 0.082 mg. Weight loss percentage: 4.634%. Enthalpy (normalized): 3.2707 J / g; Onset x: 69.98° C.; Peak temperature: 78.37° C. Enthalpy (normalized): 0.83635 J / g; Peak temperature: 151.31° C. [Figure 83] TG / DSC thermogram of pattern 5 of AP1189 cyclamate. Weight loss: 0.070 mg. Weight loss percentage: 1.696%. Enthalpy (normalized): 0.68855 J / g; Onset x: 140.91° C.; Peak temperature: 146.39° C. [Figure 84] TG / DSC thermogram of pattern 1 of AP1189 formic acid. Weight loss: 0.008 mg. Weight loss percentage: 3.049%. Enthalpy (normalized): 7.5282 J / g; Onset x: 169.12° C.; Peak temperature: 171.97° C. [Figure 85] TG / DSC thermogram of AP1189 L-lactic acid pattern 1. Weight loss: 0.026 mg. Weight loss percentage: 0.859%. Enthalpy (normalized): 31.499 J / g. Onset x: 189.47° C. Peak temperature: 192.80° C. [Figure 86] TG / DSC thermogram of AP1189DL-lactic acid pattern 1. Weight loss: 0.034 mg. Weight loss percentage: 1.476%. Enthalpy (normalized): 2.2523 J / g; Onset x: 198.48° C.; Peak temperature: 200.63° C. [Figure 87]Figure 2 shows the TG / DSC thermogram of Pattern 1 of AP1189 glutaric acid. Weight loss: 0.27 mg. Weight loss percentage: 1.256%. Enthalpy (normalized): 0.0964 J / g; Onset x: 109.24°C; Peak temperature: 115.31°C. Enthalpy (normalized): 16.647 J / g; Onset x: 159.93°C; Peak temperature: 164.02°C. [Figure 88] TG / DSC thermogram of AP1189 glutaric acid pattern 2. Weight loss: 0.019 mg. Weight loss percentage: 1.001%. Enthalpy (normalized): 48.550 J / g; Onset x: 162.77° C.; Peak temperature: 165.94° C. [Figure 89] TG / DSC thermogram of AP1189 glutaric acid pattern 4. Weight loss: 0.010 mg. Weight loss percentage: 1.764%. Enthalpy (normalized): 18.475 J / g; Onset x: 114.55° C.; Peak temperature: 148.15° C. Enthalpy (normalized): 10.102 J / g; Onset x: 160.45° C.; Peak temperature: 163.28° C. [Figure 90] TG / DSC thermogram of AP1189 adipic acid pattern 1. Weight loss: 0.015 mg. Weight loss percentage: 6.117%. Enthalpy (normalized): 12.428 J / g. Onset x: 183.34° C.; Peak temperature: 187.98° C. [Figure 91] FIG. 1 shows the XRPD diffractogram of pattern 4 of AP1189 glutaric acid. [Figure 92] 1 shows the IR spectrum of pattern 1 of AP1189 acetate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] definition "Compound of formula I", "Compound I" and "AP1189" refer to a compound of formula I: [ka] and tautomers and stereoisomers thereof. Another name for the compound is N"-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

[0029] In some cases, the term "AP1189" may refer to the free base structure of formula I or to the acetate salt of AP1189. Preferably, the term "AP1189 free base" refers to the structure of formula I. Preferably, the term "AP1189 acetate" refers to the acetate salt of the structure of formula I.

[0030] As used herein, the term "SP1189" refers to the succinate salt of the structure of Formula I. The terms "SP1189" and "AP1189 succinate salt" are synonymous as used herein.

[0031] With regard to the naming of salts, terms such as "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine acetate" and "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene)-aminoguanidinium acetate" are synonymous, i.e., when the anion is written immediately after "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine", the protonated form of "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium" is meant, i.e., "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene)-aminoguanidinium". Similarly, when an acid is listed as part of the name of a protonated compound, e.g., "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetic acid," the unprotonated form of the compound means, e.g., "N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetic acid." These considerations also apply to other salts of the disclosed compounds.

[0032] In one embodiment, the compound of the disclosure is N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, including its tautomers and stereoisomers. In one embodiment, the compound of the disclosure is {(1E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, including its tautomers and stereoisomers. In one embodiment, the compound of the disclosure is N"-[(E)-[3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene}-amino]guanidine, including its tautomers and stereoisomers.

[0033] In one embodiment, the compound of the disclosure is N-{(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, including its tautomers and stereoisomers. In one embodiment, the compound of the disclosure is N"-[[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]-amino]guanidine, including its tautomers and stereoisomers.

[0034] In one embodiment, the compound of the disclosure is N-{(1E,2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]arylidene}-aminoguanidine (also referred to herein as (E)-N-trans-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine), including its tautomers. In one embodiment, the compound of the present disclosure is N"-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, including its tautomers. These compounds may also appear as salts and the corresponding crystalline forms disclosed herein. In one embodiment, the compound of the present disclosure is N-{(1Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, N-{(2Z)-3-[1- (2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, N-{(1Z,2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, N-{(1Z,2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine, and N-{(1E,2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine.

[0035] In one embodiment, the compounds of the present disclosure include N"-[(Z)-[3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, N"-[[(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, N"-[(Z)- ... N"-[(Z)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, N"-[(Z)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, and N"-[(E)-[(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

[0036] In a preferred embodiment, the alkene portion of the compound is in the E configuration and the imine portion is in the Z or E configuration. In one embodiment, the compound is a mixture of N"-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine and N"-[(Z)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

[0037] The compounds of the present disclosure may further be any tautomer of the above structure. As used herein, "tautomer" refers to other structural isomers that exist in equilibrium as a result of the migration of a hydrogen atom. When reporting the results of a measurement, such as the measurement of 2-theta values, for example reading the 2-theta values ​​from an XRPD diffractogram, one of skill in the art will understand that the method of measuring this value inherently includes some uncertainty. For example, the measurement of 2-theta values ​​may have an uncertainty of 0.2°.

[0038] The crystalline "Form A" of AP1189 acetate corresponds to AP1189 acetate Pattern 1 as disclosed herein. αIt refers to a crystalline form of AP1189 acetate that exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. The crystalline "Form B" of AP1189 succinate corresponds to AP1189 succinate Pattern 1 as disclosed herein. α It refers to a crystalline form of AP1189 succinate that exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0039] Unless otherwise specified, 2 theta values ​​are in degrees (°).

[0040] "Onset temperature" refers to the designed intersection of the extrapolated baseline and the tangent to the inflection at the onset of melting.

[0041] As used herein, "seeding" refers to the technique of adding "seed" crystals to a crystallization solution to promote the formation of crystals. Preferably, the composition of the seed crystals is the same as the composition of the crystals that are formed.

[0042] compound In one embodiment, the present disclosure provides the compound AP1189, specifically its salts. One embodiment provides the compound AP1189, including its tautomers and / or isomeric forms, such as its enantiomeric forms and / or its diastereomeric forms. In one embodiment, the diastereomeric forms include the cis and trans forms of the compound, particularly with respect to the alkene moiety. The compound may also exist as either the E or Z form with respect to the C=N double bond of the structure of formula I. Those skilled in the art will appreciate that in certain cases the E configuration is synonymous with the trans configuration, and in certain cases the Z configuration is synonymous with the cis configuration. For example, in certain cases where both atoms forming part of the double bond are each bonded to a hydrogen moiety or exactly one further moiety that is not an isolated pair. One embodiment of the present disclosure provides an acetate salt of AP1189. Another embodiment of the present disclosure provides a succinate salt of AP1189. In one embodiment, the term "compound of the present disclosure" refers to crystalline form A of AP1189 acetate. In one embodiment, the term "compound of the present disclosure" refers to crystalline form B of AP1189 succinate.

[0043] In some embodiments, a pharma- ceutically acceptable salt of AP1189 is (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium acetate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium succinate, including its tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine DL-mandelic acid, including their tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine hippuric acid, including their tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine L-lactic acid, including their tautomeric and stereoisomeric forms; >50 mM (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium besylate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium oxoglutarate, including its tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine formic acid, including their tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine DL-lactic acid, including their tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine glutaric acid, including their tautomeric and stereoisomeric forms; Salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine adipic acid, including their tautomeric and stereoisomeric forms; and The compound is selected from the group consisting of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium nitrate, including its tautomeric and stereoisomeric forms.

[0044] In one embodiment, the pharma- ceutically acceptable salt of AP1189 is selected from the group consisting of acetate of AP1189, succinate of AP1189, DL-mandelic acid salt of AP1189, hippuric acid salt of AP1189, L-lactic acid salt of AP1189, besylate of AP1189, oxoglutarate of AP1189, formic acid salt of AP1189, DL-lactic acid salt of AP1189, glutaric acid salt of AP1189, adipic acid salt of AP1189 and nitrate of AP1189.

[0045] In one embodiment, (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium napadisilate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium esylate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium edisylate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium cyclamate, including its tautomeric and stereoisomeric forms; (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidinium oxalate, including its tautomeric and stereoisomeric forms; and The salt of AP1189 is selected from the group consisting of salts of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl-allylideneamino]-guanidine (+)-camphor-10-sulfonic acid, including its tautomeric and stereoisomeric forms.

[0046] The terms "treatment" and "treating" as used herein refer to the management and care of a subject for the purpose of combating a condition, disease or disorder. The term is intended to include all therapies for a given condition suffered by the subject. The subject to be treated is preferably a mammal, in particular a human. However, treatment of animals such as mice, rats, dogs, cats, horses, cows, sheep and pigs is also within the scope of the invention. The subject to be treated can be of various ages.

[0047] One aspect of the present disclosure is to provide an oral formulation as disclosed herein comprising a crystalline form of an AP1189 salt as disclosed herein for use in treating a disease or disorder in a subject, wherein the subject being treated is a mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a livestock animal. In some embodiments, the mammal is selected from the group consisting of a mouse, a rat, a dog, a cat, a horse, a cow, a sheep, and a pig.

[0048] Crystal morphology The present disclosure relates to a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt. The object of the present disclosure is to provide a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt that has a high solubility in aqueous media, especially at low pH. Similarly, the object of the present disclosure is to provide a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt that has a high solubility in aqueous media, especially at low pH.

[0049] The crystalline forms of AP1189 and its salts may be characterized by X-ray powder diffraction (XRPD) analysis. Such analysis may be performed using a suitable X-ray powder diffractometer, such as a PANalytical X'pert pro equipped with a PIXcel detector (128 channels). Scanning of the sample may be performed between 3 and 35°2θ. The sample may be gently ground to free aggregates before the measurement. To support the sample, the sample may be loaded onto a multi-well plate with a polymeric film of Kapton or Mylar. Measurements may be performed by placing the multi-well plate in the diffractometer and subsequently analyzing using Cu K radiation (α1 λ=1.54060 Å; α2=1.54443 Å; β=1.39225 Å; α1:α2 ratio=0.5) running in transmission mode (step width 0.0130°2θ, step time 18.87 s) using a generator setting of 40 kV / 40 mA.

[0050] Table 1 provides an overview of the polymorphs disclosed herein. [Table 1] JPEG2024523459000004.jpg139159

[0051] AP1189 Acetate Form A The present disclosure provides crystalline form A of AP1189 acetate. Crystalline form A of AP1189 acetate exhibits an XRPD diffractogram as shown in Figure 1. One embodiment of the present disclosure has Cu K at 11.5±0.2, 23.5±0.2 and 27.0±0.2. α Crystalline form A of AP1189 acetate is provided, which exhibits at least X-ray lines (2-theta values) in a powder diffraction pattern as measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 11.7±0.2, 13.0±0.2, 15.5±0.2, 15.6±0.2, 16.2±0.2, 19.6±0.2, 20.0±0.2, 21.1±0.2 and 24.8±0.2. α The present disclosure provides a crystalline form A of AP1189 acetate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. α Provided is a crystalline form A of AP1189 acetate, which exhibits an X-ray pattern (2 theta value) in powder diffraction as measured using radioactive material.

[0052] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.1, 11.5, 11.7, 12.2, 13.0, 15.5, 15.6, 15.9, 16.2, 18.3, 18.6, 19.6, 20.0, 20.6, 21.1, 21.5, 21.8, 22.3, 23.5, 24.8, 25.7, 27.0, 27.5, 28.2, 28.5, 30.2, 30.7, 31.2, 32.3, 32.9, 33.4, and 34.3. αCrystalline form A of AP111189 acetate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 6.1±0.2, 11.5±0.2, 11.7±0.2, 12.2±0.2, 13.0±0.2, 15.5±0.2, 15.6±0.2, 15.9±0.2, 16.2±0.2, 18.3±0.2, 18.6±0.2, 19.6±0.2, 20.0±0.2, 20.6±0.2, 21.1±0.2, 21.5±0.2, 21.7±0.2, 21.8±0.2, 22.7±0.2, 23.3±0.2, 24.2±0.2, 25.0±0.2, 26.0±0.2, 27.0±0.2, 28.0±0.2, 29.0±0.2, 30.0±0.2, 31.0±0.2, 32.0±0.2, 33.0±0.2, 34.0±0.2, 35.0±0.2, 36.0±0.2, 37.0±0.2, 38.0±0.2, 39.0±0.2, 40.0±0.2, 41.0±0.2, 42.0±0.2, 43.0±0.2, 44.0±0.2, 45.0±0.2, 46.0±0.2, 47.0±0.2, 48.0±0.2, 49.0±0.2, 0.8±0.2, 22.3±0.2, 23.5±0.2, 24.8±0.2, 25.7±0.2, 27.0±0.2, 27.5±0.2, 28.2±0.2, 28.5±0.2, 30.2±0.2, 30.7±0.2, 31.2±0.2, 32.3±0.2, 32.9±0.2, 33.4±0.2, and 34.3±0.2. α The present disclosure provides a crystalline form A of AP1189 acetate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form A of AP1189 acetate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form A of AP1189 acetate, which exhibits a Cu K value selected from the group consisting of 11.5, 11.7, 13.0, 15.5, 15.6, 16.2, 19.6, 20.0, 21.1, 23.5, 24.8 and 27.0. α Crystalline form A of AP1189 acetate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 11.5±0.2, 11.7±0.2, 13.0±0.2, 15.5±0.2, 15.6±0.2, 16.2±0.2, 19.6±0.2, 20.0±0.2, 21.1±0.2, 23.5±0.2, 24.8±0.2, and 27.0±0.2. α Crystalline form A of AP1189 acetate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2-based crystalline form A of AP1189 acetate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. αCrystalline form A of AP1189 acetate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0053] AP1189 Acetate Form I Another crystalline form of AP1189 acetate is identified herein, which exhibits a mixture of XRPD pattern 1 and XRPD pattern 2. In a preferred embodiment, crystalline form A of AP1189 acetate is substantially free of polymorphs of AP1189 acetate that give rise to XRPD pattern 2. In one embodiment, "substantially free" means that crystalline form A of AP1189 acetate contains less than 90% of the polymorphs of AP1189 acetate that give rise to XRPD pattern 2, e.g. less than 80%, such as less than 70%, for example less than 60%, such as less than 50%, for example less than 40%, for example less than 30%, such as less than 20%, for example less than 15%, for example less than 10%, for example less than 5% of the polymorphs of AP1189 acetate that give rise to XRPD pattern 2. The content of the polymorphs of AP1189 acetate that give rise to XRPD pattern 2 may be assessed by the intensity of the X-ray lines of pattern 2 relative to the intensity of the X-ray lines of pattern 1 of AP1189 acetate. For example, pattern 2 exhibits X-ray lines at 14.9, 18.0 and 24.2 that do not overlap with X-ray lines (2-theta values) originating from AP1189 pattern 1. Thus, one embodiment of the present disclosure provides crystalline form A of AP1189 acetate that is substantially free of a second crystalline form of AP1189 acetate, the second crystalline form of AP1189 acetate exhibiting Cu K values ​​at 14.9±0.2, 18.0±0.2 and / or 24.2±0.2. α It exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a crystalline form A of AP1189 acetate substantially free of a second crystalline form of AP1189 acetate, the second crystalline form of AP1189 acetate exhibiting Cu K at 14.9, 18.0 and / or 24.2. αWhen measured using radioactive materials, it exhibits X-ray lines (2-theta values) in a powder diffraction pattern. In one embodiment of the present disclosure, crystalline form A of AP1189 acetate does not exhibit X-ray lines at 14.9±0.2, 18.0±0.2 and / or 24.2±0.2 in a powder diffraction pattern, or crystalline form A of AP1189 acetate exhibits lines at 14.9±0.2, 18.0±2 and / or 24.2±0.2 with a relative intensity of less than 30%, such as less than 25%, for example less than 20%, such as less than 15%, for example less than 10%, for example less than 5%.

[0054] AP1189 succinate form B The present disclosure provides crystalline form B of AP1189 succinate. The crystalline form B of AP1189 succinate exhibits an XRPD diffractogram as shown in Figure 6. One embodiment of the present disclosure has Cu K at 9.7±0.2, 22.8±0.2 and 26.7±0.2. α Crystalline form B of AP1189 succinate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 5.4±0.2, 13.4±0.2, 16.3±0.2 and 19.5±0.2. α Crystalline form B of AP1189 succinate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 12.2±0.2, 15.8±0.2, 21.8±0.2 and 28.5±0.2. α The present disclosure provides a crystalline form B of AP1189 succinate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Provided is a crystalline form B of AP1189 succinate, which exhibits an X-ray pattern (2 theta value) in powder diffraction when measured using radioactivity.

[0055] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.4, 9.7, 12.2, 12.7, 13.4, 13.6, 15.8, 16.3, 18.1, 18.6, 18.9, 19.5, 19.9, 21.1, 21.8, 21.8, 22.0, 22.2, 22.4, 22.8, 23.4, 23.7, 24.6, 25.0, 25.3, 26.1, 26.3, 26.7, 27.5, 28.5, 29.1, 29.4, 30.0, 31.5, 32.3, 32.7, 33.6, and 34.1. α Crystalline form B of AP1189 succinate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the disclosure is 5.4±0.2, 9.7±0.2, 12.2±0.2, 12.7±0.2, 13.4±0.2, 13.6±0.2, 15.8±0.2, 16.3±0.2, 18.1±0.2, 18.6±0.2, 18.9±0.2, 19.5±0.2, 19.9±0.2, 21.1±0.2, 21.8±0.2, 21.8±0.2, 22.0±0.2, 22.2±0.2, 22.4±0.2, 22. 8±0.2, 23.4±0.2, 23.7±0.2, 24.6±0.2, 25.0±0.2, 25.3±0.2, 26.1±0.2, 26.3±0.2, 26.7±0.2, 27.5±0.2, 28.5±0.2, 29.1±0.2, 29.4±0.2, 30.0±0.2, 31.5±0.2, 32.3±0.2, 32.7±0.2, 33.6±0.2, and 34.1±0.2. α The present invention provides a crystalline form B of AP1189 succinate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form B of AP1189 succinate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form B of AP1189 succinate, which exhibits Cu K values ​​selected from the group consisting of 5.4, 9.7, 12.2, 13.4, 15.8, 16.3, 19.5, 21.8, 22.8, 26.7, and 28.5. αCrystalline form B of AP1189 succinate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 5.4±0.2, 9.7±0.2, 12.2±0.2, 13.4±0.2, 15.8±0.2, 16.3±0.2, 19.5±0.2, 21.8±0.2, 22.8±0.2, 26.7±0.2, and 28.5±0.2. α Crystalline form B of AP1189 succinate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 7. α Crystalline form B of AP1189 succinate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0056] AP1189 Acetate Form II One embodiment provides a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate, which may be converted to AP1189 acetate in crystalline form A. One embodiment provides crystalline form I of AP1189 acetate, which corresponds to XRPD patterns 1 and 2. One particular embodiment is a Cu K at one or more of 11.5±0.2, 11.7±0.2, 12.9±0.2, 14.9±0.2, 15.4±0.2, 15.6±0.2, 18.0±0.2, 19.9±0.2, 20.0±0.2, 21.1±0.2, 21.5±0.2, 21.8±0.2, 22.4±0.2, 23.5±0.2, 24.2±0.2, 24.7±0.2, and 26.9±0.2. α Crystalline Form I of AP1189 acetate is provided, which exhibits X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. One embodiment is a crystalline form I of AP1189 acetate, which exhibits X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. αCrystalline form I of AP1189 acetate is provided, which exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides crystalline form II of AP1189 acetate, which corresponds to XRPD pattern 3. A particular embodiment has Cu K at one or more of 7.5±0.2, 9.4±0.2, 12.8±0.2, 13.3±0.2, 14.2±0.2, 15.3±0.2, 16.0±0.2, 17.0±0.2, 18.8±0.2, 19.7±0.2, 20.3±0.2, 21.1±0.2, 21.4±0.2, 21.9±0.2, 22.0±0.2, 22.7±0.2, and 23.1±0.2. α Crystalline Form II of AP1189 acetate is provided, which exhibits X-ray (2-theta) values ​​in the powder diffraction pattern when measured using radioactive materials. One embodiment is a crystalline form II of AP1189 acetate, which exhibits X-ray (2-theta) values ​​in the powder diffraction pattern when measured using radioactive materials. α Crystalline Form II of AP1189 acetate is provided, which exhibits X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactivity.

[0057] Solid and / or amorphous forms of AP1189 One embodiment of the present disclosure provides a solid form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate.One embodiment of the present disclosure provides a solid amorphous form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate.

[0058] AP1189 tosylate form C The present disclosure also provides crystalline form C of AP1189 tosylate. Crystalline form C of AP1189 tosylate exhibits an XRPD diffractogram as shown in Figure 4. One embodiment of the present disclosure has Cu K at 14.5±0.2, 21.0±0.2, and 25.2±0.2. αThe present disclosure provides a crystalline form C of AP1189 tosylate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. In one embodiment of the disclosure, the crystalline form C of AP1189 tosylate exhibits a Cu K value selected from the group consisting of 13.4±0.2 and 16.0±0.2. α It further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. In one embodiment of the present disclosure, the crystalline form C of AP1189 tosylate has a Cu K value selected from the group consisting of 8.0±0.2, 9.4±0.2, 10.0±0.2, 15.3±0.2, 16.7±0.2, 17.6±0.2, 19.2±0.2, 19.8±0.2, 21.3±0.2, and 25.4±0.2. α In one embodiment, the crystalline form C of AP1189 tosylate further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α When measured using radiation, powder diffraction gives an X-ray pattern (2 theta value).

[0059] One embodiment of the present disclosure is a Cu K selected from the group consisting of 8.0, 9.4, 10.0, 10.8, 12.1, 12.3, 13.4, 14.1, 14.5, 15.3, 15.7, 16.0, 16.7, 17.6, 19.2, 19.8, 20.0, 20.7, 21.0, 21.3, 22.0, 22.4, 22.7, 22.8, 23.1, 23.6, 24.1, 24.3, 25.2, 25.4, 25.7, 26.1, 26.7, 27.1, 27.7, 28.1, 29.0, 29.2, 29.9, 30.3, 30.7, 31.4, 32.7, 33.2, 33.5, and 34.1, 34.6. α The present invention provides a crystalline form C of AP1189 tosylate salt, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure is 8.0±0.2, 9.4±0.2, 10.0±0.2, 10.8±0.2, 12.1±0.2, 12.3±0.2, 13.4±0.2, 14.1±0.2, 14.5±0.2, 15.3±0.2, 15.7±0.2, 16.0±0.2, 16.7±0.2, 17.6±0.2, 19.2±0.2, 19.8±0.2, 20.0±0.2, 20.7±0.2, 21.0±0.2, 21.3±0.2, 22.0±0.2, 22.4±0.2, 22.7±0.2, 22.8±0.2, 22.9±0.2, 23.0±0.2, 23.1±0.2, 23.2±0.2, 23.3±0.2, 23.4±0.2, 24.1±0.2, 24.2±0.2, 24.3±0.2, 24.4±0.2, 25.0±0.2, 25.1±0.2, 26.0±0.2, 26.1±0.2, 27.0 ... 0.8±0.2, 23.1±0.2, 23.6±0.2, 24.1±0.2, 24.3±0.2, 25.2±0.2, 25.4±0.2, 25.7±0.2, 26.1±0.2, 26.7±0.2, 27.1±0.2, 27.7±0.2, 28.1±0.2, 29.0±0.2, 29.2±0.2, 29.9±0.2, 30.3±0.2, 30.7±0.2, 31.4±0.2, 32.7±0.2, 33.2±0.2, 33.5±0.2, and 34.1±0.2. α The present disclosure provides a crystalline form C of AP1189 tosylate which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form C of AP1189 tosylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate which exhibits a Cu K value selected from the group consisting of 8.0, 9.4, 10.0, 13.4, 14.5, 15.3, 16.0, 16.7, 17.6, 19.2, 19.8, 21.0, 21.3, 25.2, and 25.4. α Crystalline form C of AP1189 tosylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K αCrystalline form C of AP1189 tosylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 5. α Crystalline form C of AP1189 tosylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0060] AP1189 fumarate form D The present disclosure also provides crystalline form D of AP1189 fumarate. Crystalline form D of AP1189 fumarate exhibits an XRPD diffractogram as shown in Figure 5. One embodiment of the present disclosure has Cu K at 17.6±0.2, 21.2±0.2, and 26.3±0.2. α The present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. In one embodiment of the disclosure, the crystalline form D of AP1189 fumarate exhibits a Cu K value selected from the group consisting of 11.5±0.2, 21.9±0.2, and 23.9±0.2. α It further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. In one embodiment of the present disclosure, the crystalline form D of AP1189 fumarate is selected from the group consisting of 9.2±0.2, 10.5±0.2, 10.9±0.2, 11.9±0.2, 15.8±0.2, 18.7±0.2, 19.4±0.2, 23.4±0.2, and 24.5±0.2 Cu K α In one embodiment, the crystalline form D of AP1189 fumarate has a Cu K value according to FIG. α When measured using radiation, powder diffraction gives an X-ray pattern (2 theta value).

[0061] One embodiment of the present disclosure is 8.6, 9.2, 10.2, 10.5, 10.9, 11.5, 11.9, 13.4, 15.8, 16.0, 16.4, 16.6, 17.3, 17.6, 18.2, 18.5, 18.7, 19.4, 19.6, 19.8, 20.6, 21.2, 21.4, 21.9, 22.7, 23.1, Cu K selected from the group consisting of 23.4, 23.9, 24.5, 24.8, 25.0, 26.1, 26.3, 27.0, 27.6, 28.0, 28.5, 28.8, 29.1, 29.5, 29.9, 30.3, 31.0, 31.0, 31.5, 32.0, 32.4, 33.1, 33.5, 34.2, and 34.7 α Crystalline form D of AP1189 fumarate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. An embodiment of the present disclosure is 8.6±0.2, 9.2±0.2, 10.2±0.2, 10.5±0.2, 10.9±0.2, 11.5±0.2, 11.9±0.2, 13.4±0.2, 15.8±0.2, 16.0±0.2, 16.4±0.2, 16.6±0.2, 17.3±0.2, 17.6±0.2, 18.2±0.2, 18.5±0.2, 18.7±0.2, 19.4±0.2, 19.6±0.2, 19.8±0.2, 20.6±0.2, 21.2±0.2, 21.4±0.2, 21.9±0.2, 22.7±0.2, 23.1±0.2. 2, 23.4±0.2, 23.9±0.2, 24.5±0.2, 24.8±0.2, 25.0±0.2, 26.1±0.2, 26.3±0.2, 27.0±0.2, 27.6±0.2, 28.0±0.2, 28.5±0.2, 28.8±0.2, 29.1±0.2, 29.5±0.2, 29.9±0.2, 30.3±0.2, 31.0±0.2, 31.0±0.2, 31.5±0.2, 32.0±0.2, 32.4±0.2, 33.1±0.2, 33.5±0.2, 34.2±0.2, and 34.7±0.2. αThe present invention provides a crystalline form D of AP1189 fumarate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form D of AP1189 fumarate by X-rays (2-theta values) with high relative intensity and / or by characteristic X-rays. Thus, one embodiment of the present disclosure ... Cu K lines (2-theta values) selected from the group consisting of 9.2, 10.5, 10.9, 11.5, 11.9, 15.8, 17.6, 18.7, 19.4, 21.2, 21.9, 23.4, 23.9, 24.5, 26.3 α The present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure provides a Cu K α Crystalline form D of AP1189 fumarate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 6. α Provided is a crystalline form D of AP1189 fumarate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0062] AP1189 napadisylate form III The present disclosure provides AP1189 napadisylate crystalline form III. AP1189 napadisylate crystalline form III exhibits an XRPD diffractogram as shown in Figure 14. One embodiment of the present disclosure has Cu K at 13.4±0.2, 22.2±0.2, and 26.8±0.2. αCrystalline form III of AP1189 napadisylate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 15.1±0.2, 15.5±0.2, 23.5±0.2, and 28.0±0.2. α The present disclosure provides a crystalline form III of AP1189 napadisylate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 7.6±0.2, 10.7±0.2, 12.4±0.2, and 22.8±0.2. α The present disclosure provides a crystalline form III of AP1189 napadisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline Form III of AP1189 napadisylate is provided, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactivity.

[0063] One embodiment of the present disclosure is a Cu K selected from the group consisting of 7.5, 10.7, 12.4, 13.4, 14.0, 15.1, 15.5, 17.2, 18.3, 18.8, 19.3, 20.3, 21.4, 21.8, 22.2, 22.8, 23.5, 24.3, 24.9, 25.3, 26.8, 27.1, 27.6, 28.0, 28.5, 28.9, 29.5, 29.9, 30.5, 31.4, 31.9, 32.6, and 33.5. αCrystalline form III of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 7.5±0.2, 10.7±0.2, 12.4±0.2, 13.4±0.2, 14.0±0.2, 15.1±0.2, 15.5±0.2, 17.2±0.2, 18.3±0.2, 18.8±0.2, 19.3±0.2, 20.3±0.2, 21.4±0.2, 21.8±0.2, 22.2±0.2, 22.8±0.2, 23.5±0. 2, 24.3±0.2, 24.9±0.2, 25.3±0.2, 26.8±0.2, 27.1±0.2, 27.6±0.2, 28.0±0.2, 28.5±0.2, 28.9±0.2, 29.5±0.2, 29.9±0.2, 30.5±0.2, 31.4±0.2, 31.9±0.2, 32.6±0.2, and 33.5±0.2. α The present disclosure provides AP1189 napadisylate crystalline form III, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify AP1189 napadisylate crystalline form III by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides AP1189 napadisylate crystalline form III, which exhibits a Cu K value selected from the group consisting of 7.6, 10.7, 12.4, 13.4, 15.1, 15.5, 22.2, 22.8, 23.5, 26.8, and 28.0. α The present disclosure provides a crystalline form III of AP1189 napadisylate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 7.6±0.2, 10.7±0.2, 12.4±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 22.2±0.2, 22.8±0.2, 23.5±0.2, 26.8±0.2, and 28.0±0.2. α Crystalline Form III of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 9. αCrystalline Form III of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0064] AP1189 napadisilate form IV The present disclosure provides crystalline form IV of AP1189 napadisylate. The crystalline form IV of AP1189 napadisylate exhibits an XRPD diffractogram as shown in Figure 15. One embodiment of the present disclosure has Cu K at 5.4±0.2, 15.6±0.2, and 23.4±0.2. α Crystalline form IV of AP1189 napadisylate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 18.4±0.2, 22.0±0.2, 24.2±0.2, and 25.8±0.2. α Crystalline form IV of AP1189 napadisylate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 8.5±0.2, 10.8±0.2, 12.6±0.2, 13.1±0.2, 19.5±0.2, 19.9±0.2, 21.1±0.2, 22.7±0.2, and 25.2±0.2. α The present disclosure provides a crystalline form IV of AP1189 napadisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline Form IV of AP1189 napadisylate, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactivity.

[0065] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.4, 6.5, 7.4, 8.5, 10.1, 10.8, 11.3, 12.1, 12.6, 13.1, 15.6, 16.3, 16.6, 18.4, 19.0, 19.5, 19.9, 20.3, 21.1, 22.0, 22.7, 23.4, 24.2, 25.2, 25.8, 26.9, and 30.5. αCrystalline form IV of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 5.4±0.2, 6.5±0.2, 7.4±0.2, 8.5±0.2, 10.1±0.2, 10.8±0.2, 11.3±0.2, 12.1±0.2, 12.6±0.2, 13.1±0.2, 15.6±0.2, 16.3±0.2, 16.6±0.2, 18.4±0.2 , 19.0±0.2, 19.5±0.2, 19.9±0.2, 20.3±0.2, 21.1±0.2, 22.0±0.2, 22.7±0.2, 23.4±0.2, 24.2±0.2, 25.2±0.2, 25.8±0.2, 26.9±0.2, and 30.5±0.2. α The present invention provides AP1189 napadisylate crystalline form IV, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify AP1189 napadisylate crystalline form IV by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... α Crystalline form IV of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form IV of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 10.α Crystalline Form IV of AP1189 napadisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0066] AP1189 esylate form V The present disclosure provides crystalline form V of AP1189 esylate. Crystalline form V of AP1189 esylate exhibits an XRPD diffractogram as shown in Figure 16. One embodiment of the present disclosure has Cu K at 14.5±0.2, 16.5±0.2, and 18.6±0.2. α Crystalline form V of AP1189 esylate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 9.8±0.2, 19.7±0.2, 20.1±0.2, and 26.8±0.2. α Crystalline form V of AP1189 esylate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 8.5±0.2, 10.4±0.2, 15.3±0.2, 21.9±0.2, 22.5±0.2, and 26.1±0.2. α The present disclosure provides a crystalline form V of AP1189 esylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline form V of AP1189 esylate, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0067] One embodiment of the present disclosure is a Cu K selected from the group consisting of 8.5, 9.8, 10.4, 11.3, 11.5, 13.0, 14.3, 14.5, 15.3, 16.5, 18.6, 19.7, 20.1, 21.0, 21.1, 21.9, 22.4, 23.9, 25.5, 26.1, 26.4, 26.8, 27.5, 29.7, 31.4, 32.2, and 33.5. αCrystalline form V of AP1189 esylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 8.5±0.2, 9.8±0.2, 10.4±0.2, 11.3±0.2, 11.5±0.2, 13.0±0.2, 14.3±0.2, 14.5±0.2, 15.3±0.2, 16.5±0.2, 18.6±0.2, 19.7±0.2, 20.1±0.2, 21.0±0. 2, 21.1±0.2, 21.9±0.2, 22.4±0.2, 23.9±0.2, 25.5±0.2, 26.1±0.2, 26.4±0.2, 26.8±0.2, 27.5±0.2, 29.7±0.2, 31.4±0.2, 32.2±0.2, and 33.5±0.2. α The present disclosure provides crystalline form V of AP1189 esylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form V of AP1189 esylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form V of AP1189 esylate, which exhibits Cu K values ​​selected from the group consisting of 8.5, 9.8, 10.4, 14.5, 15.3, 16.5, 18.6, 19.7, 20.1, 21.9, 22.5, 26.1, and 26.8. α Crystalline form V of AP1189 esylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form V of AP1189 esylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 11. αCrystalline form V of AP1189 esylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0068] AP1189 edisylate form VI The present disclosure provides crystalline Form VI of AP1189 edisylate. The crystalline Form VI of AP1189 edisylate exhibits an XRPD diffractogram as shown in Figure 17. One embodiment of the present disclosure has Cu K at 4.8±0.2, 12.8±0.2, and 16.5±0.2. α Crystalline form VI of AP1189 edisylate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 17.9±0.2, 21.4±0.2, 23.4±0.2, and 27.1±0.2. α Crystalline Form VI of AP1189 edisylate salt is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 9.5±0.2, 10.9±0.2, 14.3±0.2, 15.2±0.2, 18.6±0.2, and 24.5±0.2. α The present disclosure provides a crystalline form VI of AP1189 edisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α SUMMARY OF THE DISCLOSURE Provided is crystalline Form VI of AP1189 edisylate, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactivity.

[0069] One embodiment of the present disclosure is a Cu K selected from the group consisting of 4.8, 9.5, 10.9, 11.6, 12.8, 14.3, 15.2, 16.5, 17.0, 17.9, 18.6, 19.2, 20.3, 21.4, 22.5, 23.4, 24.5, 25.3, 25.5, 26.5, 27.2, 28.0, 29.5, 29.7, 30.2, 31.0, 32.6, 33.3, and 34.3. αCrystalline Form VI of AP1189 edisylic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 4.8±0.2, 9.5±0.2, 10.9±0.2, 11.6±0.2, 12.8±0.2, 14.3±0.2, 15.2±0.2, 16.5±0.2, 17.0±0.2, 17.9±0.2, 18.6±0.2, 19.2±0.2, 20.3±0.2, 21.4±0.2, 22.5±0. 2, 23.4±0.2, 24.5±0.2, 25.3±0.2, 25.5±0.2, 26.5±0.2, 27.2±0.2, 28.0±0.2, 29.5±0.2, 29.7±0.2, 30.2±0.2, 31.0±0.2, 32.6±0.2, 33.3±0.2, and 34.3±0.2. α The present invention provides crystalline form VI of AP1189 edisylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form VI of AP1189 edisylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K VI having a Cu K value selected from the group consisting of 4.8, 9.5, 10.9, 12.8, 14.3, 15.2, 16.5, 17.9, 18.6, 21.4, 23.4, 24.5, and 27.1. α Crystalline Form VI of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 4.8±0.2, 9.5±0.2, 10.9±0.2, 12.8±0.2, 14.3±0.2, 15.2±0.2, 16.5±0.2, 17.9±0.2, 18.6±0.2, 21.4±0.2, 23.4±0.2, 24.5±0.2, and 27.1±0.2. α Crystalline Form VI of AP1189 edisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 12. αCrystalline Form VI of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0070] AP1189 edisylate form VII The present disclosure provides crystalline form VII of AP1189 edisylate salt. Crystalline form VII of AP1189 edisylate salt exhibits an XRPD diffractogram as shown in Figure 18. One embodiment of the present disclosure has Cu K at 6.1±0.2, 15.7±0.2, and 23.6±0.2. α Crystalline form VII of AP1189 edisylate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 12.1, 20.1±0.2, and 21.8±0.2. α Crystalline Form VII of AP1189 edisylate salt is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 11.7±0.2, 12.7±0.2, and 19.3±0.2. α The present disclosure provides a crystalline form VII of AP1189 edisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline Form VII of AP1189 edisylate salt is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0071] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.1, 10.0, 11.7, 12.1, 12.7, 14.1, 15.7, 16.3, 17.6, 17.9, 18.3, 19.3, 20.1, 20.9, 21.8, 22.4, 22.7, 23.6, 24.3, 24.8, 25.1, 25.8, 26.5, 27.0, 27.5, 28.2, 28.6, 29.7, 30.6, 31.2, 31.9, 32.4, 32.9, 33.5, and 34.1. αCrystalline Form VII of AP1189 edisylic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 6.1±0.2, 10.0±0.2, 11.7±0.2, 12.1±0.2, 12.7±0.2, 14.1±0.2, 15.7±0.2, 16.3±0.2, 17.6±0.2, 17.9±0.2, 18.3±0.2, 19.3±0.2, 20.1±0.2, 20.9±0.2, 21.8±0.2, 22.4±0.2, 22.7±0.2, 23.6±0. 2, 24.3±0.2, 24.8±0.2, 25.1±0.2, 25.8±0.2, 26.5±0.2, 27.0±0.2, 27.5±0.2, 28.2±0.2, 28.6±0.2, 29.7±0.2, 30.6±0.2, 31.2±0.2, 31.9±0.2, 32.4±0.2, 32.9±0.2, 33.5±0.2, and 34.1±0.2. α The present disclosure provides crystalline form VII of AP1189 edisylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form VII of AP1189 edisylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 -line complex selected from the group consisting of 6.1, 11.7, 12.1, 12.7, 15.7, 19.3, 20.1, 21.8, and 23.6. α Crystalline Form VII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 6.1±0.2, 11.7±0.2, 12.1±0.2, 12.7±0.2, 15.7±0.2, 19.3±0.2, 20.1±0.2, 21.8±0.2, and 23.6±0.2. α Crystalline Form VII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure provides a Cu K2-based crystalline form VII having a Cu K2-based crystalline form VII, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. αCrystalline Form VII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0072] AP1189 edisylate form VIII The present disclosure provides crystalline form VIII of AP1189 edisylate. Crystalline form VIII of AP1189 edisylate exhibits an XRPD diffractogram as shown in Figure 19. One embodiment of the present disclosure has Cu K at 15.5±0.2, 20.7±0.2, and 21.7±0.2. α Crystalline Form VIII of AP1189 edisylate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 12.1±0.2, 13.0±0.2, and 24.1±0.2. α Crystalline Form VIII of AP1189 edisylate salt is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure has a Cu K value selected from the group consisting of 6.4±0.2 and 25.2±0.2. α The present disclosure provides a crystalline form VIII of AP1189 edisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α Crystalline Form VIII of AP1189 edisylate salt is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactivity.

[0073] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.4, 9.9, 12.1, 12.5, 13.0, 14.0, 15.5, 17.8, 18.3, 18.7, 19.5, 20.0, 20.7, 21.7, 22.2, 23.1, 24.1, 25.2, 25.7, 27.1, 27.9, 30.7, 31.1, 31.6, and 34.5. αCrystalline form VIII of AP1189 edisylic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. One embodiment of the present disclosure is a Cu K 2 O 3 solution selected from the group consisting of 6.4±0.2, 9.9±0.2, 12.1±0.2, 12.5±0.2, 13.0±0.2, 14.0±0.2, 15.5±0.2, 17.8±0.2, 18.3±0.2, 18.7±0.2, 19.5±0.2, 20.0±0.2, 20.7±0.2, 21.7±0.2, 22.2±0.2, 23.1±0.2, 24.1±0.2, 25.2±0.2, 25.7±0.2, 27.1±0.2, 27.9±0.2, 30.7±0.2, 31.1±0.2, 31.6±0.2, and 34.5±0.2. α The present disclosure provides crystalline form VIII of AP1189 edisylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form VIII of AP1189 edisylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form VIII of AP1189 edisylate, which exhibits Cu K values ​​selected from the group consisting of 6.4, 12.1, 13.0, 15.5, 20.7, 21.7, 24.1, and 25.2. α Crystalline Form VIII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 6.4±0.2, 12.1±0.2, 13.0±0.2, 15.5±0.2, 20.7±0.2, 21.7±0.2, 24.1±0.2, and 25.2±0.2. α Crystalline Form VIII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2-based crystalline form VIII having a 2-theta value selected from the group consisting of those listed in Table 14. α Crystalline Form VIII of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0074] AP1189 edisylate form IX The present disclosure provides crystalline Form IX of AP1189 edisylate. Crystalline Form IX of AP1189 edisylate exhibits an XRPD diffractogram as shown in Figure 20. One embodiment of the present disclosure has Cu K at 4.5±0.2, 16.7±0.2, and 24.7±0.2. α Crystalline form IX of AP1189 edisylate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 12.2±0.2 and 15.5±0.2. α Crystalline Form IX of AP1189 edisylate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure has a Cu K value selected from the group consisting of 9.0±0.2 and 18.0. α The present disclosure provides a crystalline form IX of AP1189 edisylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline Form IX of AP1189 edisylate, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactivity.

[0075] One embodiment of the present disclosure is a Cu K selected from the group consisting of 4.5, 9.0, 11.7, 12.2, 12.4, 13.1, 15.5, 16.7, 17.3, 18.0, 19.9, 20.4, 21.1, 22.0, 22.9, 24.7, 26.8, and 28.3. αThe present disclosure provides a crystalline form IX of AP1189 edisylic acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α The present disclosure provides crystalline form IX of AP1189 edisylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form IX of AP1189 edisylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form IX of AP1189 edisylate, which exhibits a Cu K value selected from the group consisting of 4.5, 9.0, 12.2, 15.5, 16.7, 18.0, and 24.7. α Crystalline Form IX of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 4.5±0.2, 9.0±0.2, 12.2±0.2, 15.5±0.2, 16.7±0.2, 18.0±0.2, and 24.7±0.2. α Crystalline Form IX of AP1189 edisylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 15. α Crystalline Form IX of AP1189 edisylate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0076] AP1189 Nitrate Form X The present disclosure provides crystalline form X of AP1189 nitrate. The crystalline form X of AP1189 nitrate exhibits an XRPD diffractogram as shown in Figure 21. One embodiment of the present disclosure has Cu K at 15.3±0.2, 21.4±0.2, and 25.1±0.2. α Crystalline form X of AP1189 nitrate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 11.9±0.2, 12.5±0.2, and 27.7±0.2. α The present disclosure provides a crystalline form X of AP1189 nitrate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.7±0.2, 7.5±0.2, 14.7±0.2, 17.7±0.2, and 18.1±0.2. α The present disclosure provides a crystalline form X of AP1189 nitrate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α Provided is a crystalline form X of AP1189 nitrate, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactivity.

[0077] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.7, 7.5, 11.9, 12.5, 13.1, 14.7, 15.3, 16.9, 17.7, 18.1, 18.7, 19.6, 21.4, 23.0, 24.1, 25.1, 26.6, 27.7, 29.5, and 31.7. αCrystalline form X of AP1189 nitrate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 3 K 4 K 5 K 6 K 7 K 8 K 9 K 10 K 11 K 12 K 13 K 14 K 15 K 16 K 17 K 18 K 19 K 20 K 21 K 22 K 23 K 24 K 25 K 26 K 27 K 28 K 29 K 30 K 31 K 32 K 33 K 34 K 35 K 36 K 37 K 38 K 39 ... α The present disclosure provides a crystalline form X of AP1189 nitrate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form X of AP1189 nitrate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K ion concentration selected from the group consisting of 3.7, 7.5, 11.9, 12.5, 14.7, 15.3, 17.7, 18.1, 21.4, 25.1, and 27.7. α Crystalline form X of AP1189 nitrate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.7±0.2, 7.5±0.2, 11.9±0.2, 12.5±0.2, 14.7±0.2, 15.3±0.2, 17.7±0.2, 18.1±0.2, 21.4±0.2, 25.1±0.2, and 27.7±0.2. α Crystalline form X of AP1189 nitrate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 16. α Crystalline form X of AP1189 nitrate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0078] AP1189 cyclamate form XI The present disclosure provides crystalline form XI of AP1189 cyclamate. The crystalline form XI of AP1189 cyclamate exhibits an XRPD diffractogram as shown in Figure 22. One embodiment of the present disclosure has Cu K at 7.0±0.2, 13.8±0.2, and 15.7±0.2. α Crystalline form XI of AP1189 cyclamate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 15.3±0.2, 20.7±0.2, and 21.5±0.2. α The present disclosure provides a crystalline form XI of AP1189 cyclamate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.2±0.2, 11.3±0.2, and 21.8±0.2. α The present disclosure provides a crystalline form XI of AP1189 cyclamate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline form XI of AP1189 cyclamate salt is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0079] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.2, 5.2, 7.0, 10.4, 11.3, 11.9, 13.8, 14.2, 15.3, 15.7, 16.3, 17.6, 18.5, 19.2, 20.1, 20.7, 21.5, 21.8, 22.1, 22.7, 23.4, 25.2, 26.0, and 27.8. αCrystalline form XI of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. One embodiment of the present disclosure is a Cu K 2 O 3 , selected from the group consisting of 3.2±0.2, 5.2±0.2, 7.0±0.2, 10.4±0.2, 11.3±0.2, 11.9±0.2, 13.8±0.2, 14.2±0.2, 15.3±0.2, 15.7±0.2, 16.3±0.2, 17.6±0.2, 18.5±0.2, 19.2±0.2, 20.1±0.2, 20.7±0.2, 21.5±0.2, 21.8±0.2, 22.1±0.2, 22.7±0.2, 23.4±0.2, 25.2±0.2, 26.0±0.2, and 27.8±0.2. α The present disclosure provides AP1189 cyclamate crystalline form XI, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify AP1189 cyclamate crystalline form XI by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides AP1189 cyclamate crystalline form XI, which exhibits a Cu K value selected from the group consisting of 3.2, 7.0, 11.3, 13.8, 15.3, 15.7, 20.7, 21.5, and 21.8. α The present disclosure provides a crystalline form XI of AP1189 cyclamate salt, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.2±0.2, 7.0±0.2, 11.3±0.2, 13.8±0.2, 15.3±0.2, 15.7±0.2, 20.7±0.2, 21.5±0.2, and 21.8±0.2. α Crystalline form XI of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 17. α Crystalline form XI of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0080] AP1189 cyclamate form XII The present disclosure provides AP1189 cyclamate crystalline form XII. AP1189 cyclamate crystalline form XII exhibits an XRPD diffractogram as shown in Figure 23. One embodiment of the present disclosure has Cu K at 7.3±0.2, 15.3±0.2, and 17.9±0.2. α Crystalline form XII of AP1189 cyclamate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 16.3±0.2, 19.1±0.2, 22.0±0.2, and 22.7±0.2. α The present disclosure provides a crystalline form XII of AP1189 cyclamate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 11.3±0.2, 13.1±0.2, and 16.9±0.2. α The present disclosure provides a crystalline form XII of AP1189 cyclamate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline Form XII of AP1189 cyclamate salt is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0081] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.3, 7.3, 9.3, 11.3, 12.7, 13.1, 14.8, 15.3, 16.3, 16.9, 17.9, 19.1, 19.3, 20.1, 22.0, 22.7, 24.1, 24.8, 25.8, 27.1, 28.0, and 29.0. αCrystalline form XII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. One embodiment of the present disclosure is a Cu K 2 O 3 solution selected from the group consisting of 6.3±0.2, 7.3±0.2, 9.3±0.2, 11.3±0.2, 12.7±0.2, 13.1±0.2, 14.8±0.2, 15.3±0.2, 16.3±0.2, 16.9±0.2, 17.9±0.2, 19.1±0.2, 19.3±0.2, 20.1±0.2, 22.0±0.2, 22.7±0.2, 24.1±0.2, 24.8±0.2, 25.8±0.2, 27.1±0.2, 28.0±0.2, and 29.0±0.2. α The present disclosure provides AP1189 cyclamate crystalline form XII, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify AP1189 cyclamate crystalline form XII by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides AP1189 cyclamate crystalline form XII, which exhibits Cu K values ​​selected from the group consisting of 7.3, 11.3, 13.1, 14.3, 16.3, 16.9, 17.9, 19.1, 22.0, and 22.7. α Crystalline form XII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 7.3±0.2, 11.3±0.2, 13.1±0.2, 14.3±0.2, 16.3±0.2, 16.9±0.2, 17.9±0.2, 19.1±0.2, 22.0±0.2, and 22.7±0.2. α Crystalline form XII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 18. α Crystalline form XII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0082] AP1189 cyclamate form XIII The present disclosure provides AP1189 cyclamate crystalline form XIII. AP1189 cyclamate crystalline form XIII exhibits an XRPD diffractogram as shown in Figure 24. One embodiment of the present disclosure has Cu K at 15.3±0.2, 18.5±0.2, and 18.7±0.2. α Crystalline form XIII of AP1189 cyclamate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 6.4±0.2, 14.6±0.2, 16.7±0.2, and 19.8±0.2. α Crystalline form XIII of AP1189 cyclamate salt is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 5.6±0.2, 7.1±0.2, 8.5±0.2, 10.5±0.2, 13.1±0.2, and 16.2±0.2. α The present disclosure provides a crystalline form XIII of AP1189 cyclamate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α Crystalline Form XIII of AP1189 cyclamate salt is provided, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactive material.

[0083] One embodiment of the present disclosure is 3.3, 5.6, 6.4, 7.1, 7.6, 8.5, 9.4, 9.9, 10.2, 10.5, 10.9, 11.6, 11.9, 12.3, 13.1, 13.3, 13.7, 14.1, 14.6, 15.3, 16.2, 16.7, 17.5, 18.5, 18.7, 19.8, 20.0, 20.2, 20.4, 20.6, 20.8, 20.9, 21.1, 21.2, 21.4, 21.6, 21.8, 21.8, 21.9, 22.0, 22.2, 22.4, 22.6, 22.8, 22.8, 22.9, 23.0, 23.1, 23.3, 23.7, 24.1, 24.6, 25.3, 25.4, 25.5, 26.0, 26.1, 26.2, 26.3, 26.4, 26.5, 26.6, 26.7, 27.5, 27.6, 27.8, 27.9, 28.0, 28.1, 28.2, 28.3, 28.4, 28.5, 28.6, 28.7, 29.8, 30.0, 30.1, 30.2, 30.3, 30.4, 30.5, 30.6, 30.7, 30.8, 3 Cu K selected from the group consisting of 0.2, 20.6, 21.1, 21.1, 21.3, 21.7, 22.1, 22.6, 22.8, 23.7, 24.1, 24.9, 25.1, 25.7, 26.2, 27.0, 27.7, 28.7, 29.4, 30.0, 30.8, 31.6, 32.4, and 33.6 αCrystalline form XIII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. In one embodiment of the present disclosure, the following are provided: 3.3±0.2, 5.6±0.2, 6.4±0.2, 7.1±0.2, 7.6±0.2, 8.5±0.2, 9.4±0.2, 9.9±0.2, 10.2±0.2, 10.5±0.2, 10.9±0.2, 11.6±0.2, 11.9±0.2, 12.3±0.2, 13.1±0.2, 13.3±0.2, 13.7±0.2, 14.1±0.2, 14.6±0.2, 15.3±0.2, 16.2±0.2, 16.7±0.2, 17.5±0.2, 18.5±0.2, 18.7±0.2, 19.8±0.2, 20.8±0.2, 21.6±0.2, 22.8±0.2, 23.4±0.2, 24.6±0.2, 25.0±0.2, 26.0±0.2, 27.0±0.2, 28.0±0.2, 29.0±0.2, 30.0±0.2, 31.0±0.2, 32.0±0.2, 33.0±0.2, 34.0±0.2, 35.0±0.2, 36.0±0.2, 37.0±0.2, 38.0±0.2, 39.0±0.2, 40.0±0.2, 41.0±0.2, 42.0±0.2, 43.0±0.2, 44.0± 20.2±0.2, 20.6±0.2, 21.1±0.2, 21.1±0.2, 21.3±0.2, 21.7±0.2, 22.1±0.2, 22.6±0.2, 22.8±0.2, 23.7±0.2, 24.1±0.2, 24.9±0.2, 25.1±0.2, 25.7±0.2, 26.2±0.2, 27.0±0.2, 27.7±0.2, 28.7±0.2, 29.4±0.2, 30.0±0.2, 30.8±0.2, 31.6±0.2, 32.4±0.2, and 33.6±0.2. α The present disclosure provides AP1189 cyclamate crystalline form XIII, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify AP1189 cyclamate crystalline form XIII by X-rays (2-theta values) with high relative intensity and / or by characteristic X-rays. Thus, one embodiment of the present disclosure provides AP1189 cyclamate crystalline form XIII, which exhibits a Cu K value selected from the group consisting of 5.6, 6.4, 7.1, 8.5, 10.5, 13.1, 14.6, 15.3, 16.2, 16.7, 18.5, 18.7, 19.8, 26.2, and 27.0. αCrystalline form XIII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 5.6±0.2, 6.4±0.2, 7.1±0.2, 8.5±0.2, 10.5±0.2, 13.1±0.2, 14.6±0.2, 15.3±0.2, 16.2±0.2, 16.7±0.2, 18.5±0.2, 18.7±0.2, 19.8±0.2, 26.2±0.2, and 27.0±0.2. α Crystalline form XIII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 19. α Crystalline form XIII of AP1189 cyclamate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0084] AP1189 besylate form XIV The present disclosure provides crystalline Form XIV of AP1189 besylate. Crystalline Form XIV of AP1189 besylate exhibits an XRPD diffractogram as shown in Figure 25. One embodiment of the present disclosure has Cu K at 13.0±0.2, 15.1±0.2, and 19.9±0.2. α Crystalline form XIV of AP1189 besylate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 11.2±0.2 and 18.3±0.2. α Crystalline Form XIV of AP1189 besylate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 8.3±0.2, 9.0±0.2, 16.4±0.2, and 18.7±0.2. αThe present disclosure provides a crystalline form XIV of AP1189 besylate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline Form XIV of AP1189 besylate, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0085] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.2, 8.3, 9.0, 9.9, 10.8, 11.2, 13.0, 13.1, 15.1, 16.0, 16.4, 16.7, 17.3, 18.1, 18.3, 18.7, 19.0, 19.4, 19.9, 20.3, 20.9, 21.3, 21.7, 22.0, 22.8, 23.1, 23.6, 24.8, 25.1, 25.4, 26.3, 26.5, 27.1, 28.1, 28.5, 29.8, 30.4, 31.1, 32.0, 33.2, and 34.1. α Crystalline form XIV of AP1189 besylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 3.2±0.2, 8.3±0.2, 9.0±0.2, 9.9±0.2, 10.8±0.2, 11.2±0.2, 13.0±0.2, 13.1±0.2, 15.1±0.2, 16.0±0.2, 16.4±0.2, 16.7±0.2, 17.3±0.2, 18.1±0.2, 18.3±0.2, 18.7±0.2, 19.0±0.2, 19.4±0.2, 19.9±0.2, 20.3±0.2, 20.9±0.2 , 21.3±0.2, 21.7±0.2, 22.0±0.2, 22.8±0.2, 23.1±0.2, 23.6±0.2, 24.8±0.2, 25.1±0.2, 25.4±0.2, 26.3±0.2, 26.5±0.2, 27.1±0.2, 28.1±0.2, 28.5±0.2, 29.8±0.2, 30.4±0.2, 31.1±0.2, 32.0±0.2, 33.2±0.2, and 34.1±0.2. αThe present disclosure provides crystalline form XIV of AP1189 besylate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XIV of AP1189 besylate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XIV of AP1189 besylate, which exhibits a Cu K value selected from the group consisting of 8.3, 9.0, 11.2, 13.0, 15.1, 16.4, 18.3, 18.7, and 19.9. α Crystalline Form XIV of AP1189 besylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 8.3±0.2, 9.0±0.2, 11.2±0.2, 13.0±0.2, 15.1±0.2, 16.4±0.2, 18.3±0.2, 18.7±0.2, and 19.9±0.2. α Crystalline Form XIV of AP1189 besylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 20. α Crystalline Form XIV of AP1189 besylate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0086] AP1189 oxalate form XV The present disclosure provides crystalline form XV of AP1189 oxalate. Crystalline form XV of AP1189 oxalate exhibits an XRPD diffractogram as shown in Figure 26. One embodiment of the present disclosure has Cu K at 19.5±0.2, 23.3±0.2, and 25.8±0.2. α Crystalline form XV of AP1189 oxalate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 13.9±0.2, 15.6±0.2, and 23.8±0.2. αCrystalline form XV of AP1189 oxalate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 7.2±0.2, 10.8±0.2, and 21.7±0.2. α The present disclosure provides a crystalline form XV of AP1189 oxalate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline form XV of AP1189 oxalate, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0087] One embodiment of the present disclosure is a Cu K selected from the group consisting of 7.2, 10.8, 12.1, 13.9, 14.5, 15.0, 15.6, 16.5, 16.8, 17.3, 18.2, 18.5, 19.5, 20.1, 21.7, 22.9, 23.3, 23.8, 24.3, 24.8, 25.8, 27.0, 27.9, 28.6, 29.3, 29.7, 30.2, 32.2, and 32.9. α Crystalline form XV of AP1189 oxalic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 7.2±0.2, 10.8±0.2, 12.1±0.2, 13.9±0.2, 14.5±0.2, 15.0±0.2, 15.6±0.2, 16.5±0.2, 16.8±0.2, 17.3±0.2, 18.2±0.2, 18.5±0.2, 19.5±0.2, 20.1±0.2, 21.7±0. 2, 22.9±0.2, 23.3±0.2, 23.8±0.2, 24.3±0.2, 24.8±0.2, 25.8±0.2, 27.0±0.2, 27.9±0.2, 28.6±0.2, 29.3±0.2, 29.7±0.2, 30.2±0.2, 32.2±0.2, and 32.9±0.2. αThe present disclosure provides crystalline form XV of AP1189 oxalate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XV of AP1189 oxalate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate, which exhibits a Cu K value selected from the group consisting of 7.2, 10.8, 13.9, 15.6, 19.5, 21.7, 23.3, 23.8, and 25.8. α Crystalline form XV of AP1189 oxalate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 7.2±0.2, 10.8±0.2, 13.9±0.2, 15.6±0.2, 19.5±0.2, 21.7±0.2, 23.3±0.2, 23.8±0.2, and 25.8±0.2. α Crystalline form XV of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 21. α Crystalline form XV of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0088] AP1189 oxalate form XVI The present disclosure provides crystalline form XVI of AP1189 oxalate. The crystalline form XVI of AP1189 oxalate exhibits an XRPD diffractogram as shown in Figure 26. One embodiment of the present disclosure has Cu K at 17.1±0.2, 17.9±0.2, and 19.6±0.2. α Crystalline Form XVI of AP1189 oxalate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 15.9±0.2, 24.2±0.2, 24.4±0.2, and 27.3±0.2. αCrystalline Form XVI of AP1189 oxalate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 9.5±0.2, 11.3±0.2, 21.2±0.2, and 25.4±0.2. α The present disclosure provides a crystalline form XVI of AP1189 oxalate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α Crystalline Form XVI of AP1189 oxalate salt is provided, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactive material.

[0089] One embodiment of the present disclosure is a Cu K selected from the group consisting of 9.5, 11.3, 12.1, 13.1, 14.0, 15.3, 15.9, 16.4, 17.1, 17.9, 18.9, 19.6, 20.0, 21.2, 22.0, 22.7, 23.0, 23.4, 24.2, 24.4, 24.8, 25.4, 25.7, 26.3, 27.3, 28.4, 29.9, 30.4, 31.3, 32.2, 33.3, 33.9, 34.3, and 34.9. α Crystalline Form XVI of AP1189 oxalate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 9.5±0.2, 11.3±0.2, 12.1±0.2, 13.1±0.2, 14.0±0.2, 15.3±0.2, 15.9±0.2, 16.4±0.2, 17.1±0.2, 17.9±0.2, 18.9±0.2, 19.6±0.2, 20.0±0.2, 21.2±0.2, 22.0±0.2, 22.7±0.2, 23.0±0.2, 24.0±0.2, 25.0±0.2, 26.0±0.2, 27.0±0.2, 28.0±0.2, 29.0±0.2, 30.0±0.2, 31.0±0.2, 32.0±0.2, 33.0±0.2, 34.0±0.2, 35.0±0.2, 36.0±0.2, 37.0±0.2, 38.0±0.2, 39.0±0.2, 40.0±0.2, 41.0±0.2, 42.0±0.2, 43.0±0.2, 44.0±0.2, 45.0±0.2, 46.0±0.2, 47.0±0.2, 48.0±0.2, 49.0±0.2, 50.0±0.2, 51.0±0.2, 52.0±0 0.4±0.2, 24.2±0.2, 24.4±0.2, 24.8±0.2, 25.4±0.2, 25.7±0.2, 26.3±0.2, 27.3±0.2, 28.4±0.2, 29.9±0.2, 30.4±0.2, 31.3±0.2, 32.2±0.2, 33.3±0.2, 33.9±0.2, 34.3±0.2, and 34.9±0.2. αThe present invention provides crystalline form XVI of AP1189 oxalate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XVI of AP1189 oxalate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... α Crystalline Form XVI of AP1189 oxalate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 9.5±0.2, 11.3±0.2, 15.9±0.2, 17.1±0.2, 17.9±0.2, 19.6±0.2, 21.2±0.2, 24.2±0.2, 24.4±0.2, 25.4±0.2, and 27.3±0.2. α Crystalline Form XVI of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 22. α Crystalline Form XVI of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0090] AP1189 oxalate form XVII The present disclosure provides crystalline form XVII of AP1189 oxalate. The crystalline form XVII of AP1189 oxalate exhibits an XRPD diffractogram as shown in Figure 28. One embodiment of the present disclosure has Cu K at 6.3±0.2, 10.6±0.2, and 19.8±0.2. α Crystalline Form XVII of AP1189 oxalate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 11.7±0.2, 12.3±0.2, 18.4±0.2, and 23.8±0.2. αCrystalline Form XVII of AP1189 oxalate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 14.1±0.2, 23.5±0.2, and 30.0±0.2. α The present disclosure provides a crystalline form XVII of AP1189 oxalate, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α Crystalline Form XVII of AP1189 oxalate salt is provided, which exhibits an X-ray pattern (2-theta values) in powder diffraction when measured using radioactive material.

[0091] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.3, 8.2, 10.6, 11.7, 12.3, 12.6, 12.9, 13.2, 14.1, 14.2, 15.8, 16.1, 17.1, 17.8, 18.4, 19.0, 19.2, 19.8, 20.3, 20.7, 21.0, 21.4, 21.8, 22.0, 22.3, 22.6, 23.2, 23.5, 23.8, 24.4, 24.8, 25.4, 25.9, 26.1, 26.6, 27.1, 27.5, 27.8, 28.3, 28.7, 29.0, 30.0, 31.1, 33.0, 33.7, and 34.3. αCrystalline Form XVII of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. An embodiment of the present disclosure provides the following: 6.3±0.2, 8.2±0.2, 10.6±0.2, 11.7±0.2, 12.3±0.2, 12.6±0.2, 12.9±0.2, 13.2±0.2, 14.1±0.2, 14.2±0.2, 15.8±0.2, 16.1±0.2, 17.1±0.2, 17.8±0.2, 18.4±0.2, 19.0±0.2, 19.2±0.2, 19.8±0.2, 20.3±0.2, 20.7±0.2, 21.0±0.2, 21.4±0.2, 21.8±0.2, 22. Cu K selected from the group consisting of 0±0.2, 22.3±0.2, 22.6±0.2, 23.2±0.2, 23.5±0.2, 23.8±0.2, 24.4±0.2, 24.8±0.2, 25.4±0.2, 25.9±0.2, 26.1±0.2, 26.6±0.2, 27.1±0.2, 27.5±0.2, 27.8±0.2, 28.3±0.2, 28.7±0.2, 29.0±0.2, 30.0±0.2, 31.1±0.2, 33.0±0.2, 33.7±0.2, and 34.3±0.2. α The present disclosure provides crystalline form XVII of AP1189 oxalate, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XVII of AP1189 oxalate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XVII of AP1189 oxalate, which exhibits a Cu K value selected from the group consisting of 6.3, 10.6, 11.7, 12.3, 14.1, 18.4, 19.8, 23.5, 23.8, and 30.0. α Crystalline Form XVII of AP1189 oxalate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 6.3±0.2, 10.6±0.2, 11.7±0.2, 12.3±0.2, 14.1±0.2, 18.4±0.2, 19.8±0.2, 23.5±0.2, 23.8±0.2, and 30.0±0.2. αCrystalline Form XVII of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 23. α Crystalline Form XVII of AP1189 oxalate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0092] AP1189 (+)-Camphor-10-sulfonic acid form XVIII The present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid. The crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibits an XRPD diffractogram as shown in Figure 29. One embodiment of the present disclosure has Cu K at 6.5±0.2, 11.5±0.2, and 14.8±0.2. α Crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 13.0±0.2, 13.7±0.2, 16.1±0.2, and 21.1±0.2. α The present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α The present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α The present invention provides crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactivity.

[0093] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.1, 6.5, 7.7, 9.4, 9.9, 10.4, 11.0, 11.5, 12.2, 13.0, 13.7, 14.0, 14.3, 14.8, 15.6, 15.9, 16.1, 17.2, 18.1, 18.4, 18.8, 19.8, 21.1, 21.5, 22.2, 22.7, 23.2, 23.8, 25.1, 25.7, 26.1, 27.2, 28.7, 30.1, and 31.5. α The present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits one or more X-rays (2-theta values) in the powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 5.1±0.2, 6.5±0.2, 7.7±0.2, 9.4±0.2, 9.9±0.2, 10.4±0.2, 11.0±0.2, 11.5±0.2, 12.2±0.2, 13.0±0.2, 13.7±0.2, 14.0±0.2, 14.3±0.2, 14.8±0.2, 15.6±0.2, 15.9±0.2, 16.1±0.2, 17.2±0.2, 18.3±0.2, 19.2±0.2, 20.2±0.2, 21.2±0.2, 22.2±0.2, 23.0±0.2, 24.0±0.2, 25.0±0.2, 26.0±0.2, 27.0±0.2, 28.0±0.2, 29.0±0.2, 30.0±0.2, 31.0±0.2, 32.0±0.2, 33.0±0.2, 34.0±0.2, 35.0±0.2, 36.0±0.2, 37.0±0.2, 38.0±0.2, 39.0±0.2, 40.0±0.2, 41.0±0.2, 42.0±0.2, 43.0±0.2, 44.0±0. Cu K selected from the group consisting of 18.1±0.2, 18.4±0.2, 18.8±0.2, 19.8±0.2, 21.1±0.2, 21.5±0.2, 22.2±0.2, 22.7±0.2, 23.2±0.2, 23.8±0.2, 25.1±0.2, 25.7±0.2, 26.1±0.2, 27.2±0.2, 28.7±0.2, 30.1±0.2, and 31.5±0.2 α The present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid, which exhibits one or more X-rays (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... αThe present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 6.5±0.2, 11.5±0.2, 13.0±0.2, 13.7±0.2, 14.8±0.2, 15.9±0.2, 16.1±0.2, 18.8±0.2, 19.8±0.2, and 21.1±0.2. α The present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α Crystalline form XVIII of AP1189 (+)-camphor-10-sulfonic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0094] AP1189 oxoglutarate form XIX The present disclosure provides crystalline form XIX of AP1189 oxoglutarate. Crystalline form XIX of AP1189 oxoglutarate exhibits an XRPD diffractogram as shown in Figure 30. One embodiment of the present disclosure has Cu K at 16.8±0.2, 23.4±0.2, and 23.6±0.2. α Crystalline Form XIX of AP1189 oxoglutarate is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 13.4±0.2, 16.4±0.2, 21.6±0.2, and 26.5±0.2. α Crystalline Form XIX of AP1189 oxoglutarate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 9.1±0.2, 10.7±0.2, 12.8±0.2, 13.2±0.2, 20.8±0.2, 24.1±0.2, and 24.2±0.2. αThe present disclosure provides a crystalline form XIX of AP1189 oxoglutarate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Provided is crystalline Form XIX of AP1189 oxoglutarate, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0095] One embodiment of the present disclosure is a Cu K selected from the group consisting of 9.1, 10.7, 11.8, 12.0, 12.8, 13.2, 13.4, 13.8, 14.0, 15.9, 16.4, 16.8, 17.1, 17.9, 18.3, 19.5, 20.1, 20.8, 21.6, 22.0, 22.9, 23.4, 23.6, 24.1, 24.2, 25.8, 26.5, 26.9, 27.4, 27.9, 28.9, 29.9, 30.3, 30.9, 32.3, 32.6, 33.1, 33.8, and 34.7. α Crystalline Form XIX of AP1189 oxoglutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 9.1±0.2, 10.7±0.2, 11.8±0.2, 12.0±0.2, 12.8±0.2, 13.2±0.2, 13.4±0.2, 13.8±0.2, 14.0±0.2, 15.9±0.2, 16.4±0.2, 16.8±0.2, 17.1±0.2, 17.9±0.2, 18.3±0.2, 19.5±0.2, 20.1±0.2, 20.8±0.2, 21.6±0.2, 22.0±0. 2, 22.9±0.2, 23.4±0.2, 23.6±0.2, 24.1±0.2, 24.2±0.2, 25.8±0.2, 26.5±0.2, 26.9±0.2, 27.4±0.2, 27.9±0.2, 28.9±0.2, 29.9±0.2, 30.3±0.2, 30.9±0.2, 32.3±0.2, 32.6±0.2, 33.1±0.2, 33.8±0.2, and 34.7±0.2. αThe present invention provides a crystalline form XIX of AP1189 oxoglutarate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form XIX of AP1189 oxoglutarate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... α Crystalline Form XIX of AP1189 oxoglutarate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline Form XIX of AP1189 oxoglutarate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2-2 theta value selected from the group consisting of the values ​​listed in Table 25. α Crystalline Form XIX of AP1189 oxoglutarate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0096] AP1189DL-Mandelic acid form XX The present disclosure provides crystalline form XX of AP1189DL-Mandelic acid. Crystalline form XX of AP1189DL-Mandelic acid exhibits an XRPD diffractogram as shown in Figure 31. One embodiment of the present disclosure has Cu K at 14.8±0.2, 24.2±0.2, and 25.5±0.2. αCrystalline form XX of AP1189DL-mandelic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment is a crystal form XX of AP1189DL-mandelic acid, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment is a crystal form XX of AP1189DL-mandelic acid, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. α Crystalline form XX of AP1189DL-Mandelic acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 5.3±0.2, 12.4±0.2, 13.3±0.2, 16.0±0.2, 16.8±0.2, 17.9±0.2, 21.2±0.2, and 24.8±0.2. α The present disclosure provides a crystalline form XX of AP1189DL-Mandelic acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α SUMMARY OF THE DISCLOSURE Provided is crystalline form XX of AP1189 DL-Mandelic acid, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0097] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.3, 9.6, 10.0, 10.7, 10.9, 11.7, 12.0, 12.4, 13.3, 13.9, 14.8, 15.3, 16.0, 16.8, 17.0, 17.3, 17.6, 17.9, 18.5, 19.1, 19.8, 20.2, 20.7, 21.2, 21.5, 21.8, 22.9, 24.2, 24.5, 24.8, 25.5, 26.4, 26.9, 27.1, 27.5, 28.1, 28.4, 29.7, 30.3, 31.2, 32.4, 32.8, 33.1, 33.5, 34.4, and 34.7. αCrystalline form XX of AP1189 DL-mandelic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. One embodiment of the present disclosure provides 5.3±0.2, 9.6±0.2, 10.0±0.2, 10.7±0.2, 10.9±0.2, 11.7±0.2, 12.0±0.2, 12.4±0.2, 13.3±0.2, 13.9±0.2, 14.8±0.2, 15.3±0.2, 16.0±0.2, 16.8±0.2, 17.0±0.2, 17.3±0.2, 17.6±0.2, 17.9±0.2, 18.5±0.2, 19.1±0.2, 19.8±0.2, 20.2±0.2, 20.7±0.2, 21. 2±0.2, 21.5±0.2, 21.8±0.2, 22.9±0.2, 24.2±0.2, 24.5±0.2, 24.8±0.2, 25.5±0.2, 26.4±0.2, 26.9±0.2, 27.1±0.2, 27.5±0.2, 28.1±0.2, 28.4±0.2, 29.7±0.2, 30.3±0.2, 31.2±0.2, 32.4±0.2, 32.8±0.2, 33.1±0.2, 33.5±0.2, 34.4±0.2, and 34.7±0.2. α The present invention provides crystalline form XX of AP1189DL-Mandelic acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XX of AP1189DL-Mandelic acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XX of AP1189DL-Mandelic acid, which exhibits a Cu K value selected from the group consisting of 5.3, 9.6, 10.0, 12.4, 13.3, 14.8, 16.0, 16.8, 17.9, 19.1, 21.2, 21.5, 24.2, 24.8, and 25.5. αCrystalline form XX of AP1189DL-Mandelic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form XX of AP1189DL-Mandelic acid is provided, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2 value selected from the group consisting of the 2-theta values ​​listed in Table 26. α Crystalline form XX of AP1189 DL-mandelic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0098] AP1189DL-Mandelic acid form XXI The present disclosure provides crystalline form XXI of AP1189DL-Mandelic acid. Crystalline form XXI of AP1189DL-Mandelic acid exhibits an XRPD diffractogram as shown in Figure 32. One embodiment of the present disclosure has Cu K at 5.4±0.2, 10.0±0.2, and 24.6±0.2. α Crystalline form XXI of AP1189DL-mandelic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 9.8±0.2, 16.6±0.2, 18.1±0.2, and 21.1±0.2. α Crystalline Form XXI of AP1189DL-Mandelic Acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 12.7±0.2, 13.5±0.2, 21.7±0.2, and 25.4±0.2. αCrystalline Form XXI of AP1189DL-Mandelic Acid is provided, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline Form XXI of AP1189DL-Mandelic Acid is provided, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0099] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.4, 9.8, 10.0, 11.2, 11.5, 11.8, 12.7, 13.5, 14.4, 15.0, 15.5, 15.7, 15.8, 16.6, 17.2, 18.1, 19.6, 20.2, 20.7, 21.1, 21.7, 22.6, 23.3, 23.6, 24.6, 25.4, 26.1, 27.0, 27.3, 28.7, 29.0, 29.8, 30.4, 30.7, 31.2, 32.8, 33.5, 34.0, and 34.5. α Crystalline Form XXI of AP1189DL-Mandelic Acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 5.4±0.2, 9.8±0.2, 10.0±0.2, 11.2±0.2, 11.5±0.2, 11.8±0.2, 12.7±0.2, 13.5±0.2, 14.4±0.2, 15.0±0.2, 15.5±0.2, 15.7±0.2, 15.8±0.2, 16.6±0.2, 17.2±0.2, 18.1±0.2, 19.6±0.2, 20.2±0.2, 20.7±0.2, 21.1±0. 2, 21.7±0.2, 22.6±0.2, 23.3±0.2, 23.6±0.2, 24.6±0.2, 25.4±0.2, 26.1±0.2, 27.0±0.2, 27.3±0.2, 28.7±0.2, 29.0±0.2, 29.8±0.2, 30.4±0.2, 30.7±0.2, 31.2±0.2, 32.8±0.2, 33.5±0.2, 34.0±0.2, and 34.5±0.2. αThe present disclosure provides crystalline form XXI of AP1189DL-mandelic acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXI of AP1189DL-mandelic acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XXI of AP1189DL-mandelic acid, which exhibits a Cu K value selected from the group consisting of 5.4, 9.8, 10.0, 12.7, 13.5, 16.6, 18.1, 21.1, 21.7, 24.6, and 25.4. α Crystalline Form XXI of AP1189DL-Mandelic Acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline Form XXI of AP1189DL-Mandelic Acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K2-2 theta value selected from the group consisting of the values ​​listed in Table 27. α Crystalline Form XXI of AP1189DL-Mandelic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0100] AP1189 Morphology of Hippuric Acid XXII The present disclosure provides AP1189 Hippuric Acid Crystalline Form XXII. AP1189 Hippuric Acid Crystalline Form XXII exhibits an XRPD diffractogram as shown in Figure 33. One embodiment of the present disclosure has Cu K at 20.1±0.2, 24.1±0.2, and 24.5±0.2. α The crystalline form XXII of AP1189 hippuric acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 10.9±0.2, 11.5±0.2, 14.4±0.2, 14.9±0.2, and 18.1±0.2.α The present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 9.6±0.2, 14.1±0.2, and 15.5±0.2. α The present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α Provided is crystalline form XXII of AP1189 hippuric acid, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0101] One embodiment of the present disclosure is a Cu K selected from the group consisting of 8.6, 9.6, 9.8, 10.9, 11.5, 11.8, 12.7, 13.3, 13.8, 14.1, 14.4, 14.9, 15.5, 16.4, 17.5, 18.1, 19.5, 20.1, 20.7, 21.0, 22.0, 22.4, 22.8, 23.1, 24.1, 24.5, 25.3, 25.8, 27.1, 28.1, and 29.1. α The present disclosure provides crystalline form XXII of AP1189 hippuric acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure includes 8.6±0.2, 9.6±0.2, 9.8±0.2, 10.9±0.2, 11.5±0.2, 11.8±0.2, 12.7±0.2, 13.3±0.2, 13.8±0.2, 14.1±0.2, 14.4±0.2, 14.9±0.2, 15.5±0.2, 16.4±0.2, 17.5±0.2, 18.1±0.2 , 19.5±0.2, 20.1±0.2, 20.7±0.2, 21.0±0.2, 22.0±0.2, 22.4±0.2, 22.8±0.2, 23.1±0.2, 24.1±0.2, 24.5±0.2, 25.3±0.2, 25.8±0.2, 27.1±0.2, 28.1±0.2, and 29.1±0.2. αThe present invention provides crystalline form XXII of AP1189 hippuric acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXII of AP1189 hippuric acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits Cu K values ​​selected from the group consisting of 9.6, 10.9, 11.5, 14.1, 14.4, 14.9, 15.5, 18.1, 20.1, 24.1, and 24.5. α The present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α The present disclosure provides crystalline form XXII of AP1189 hippuric acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 28. α Crystalline form XXII of AP1189 hippuric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0102] AP1189 formic acid form XXIII The present disclosure provides crystalline form XXIII of AP1189 formate. Crystalline form XXIII of AP1189 formate exhibits an XRPD diffractogram as shown in Figure 34. One embodiment of the present disclosure has Cu K at 13.3±0.2, 15.1±0.2, and 25.6±0.2. α Crystalline form XXIII of AP1189 formate salt is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 17.3±0.2, 18.9±0.2, 21.8±0.2, and 23.6±0.2. αCrystalline Form XXIII of AP1189 formate is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α The present disclosure provides a crystalline form XXIII of AP1189 formate, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline form XXIII of AP1189 formate salt is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0103] One embodiment of the present disclosure is a Cu K selected from the group consisting of 7.4, 10.4, 10.6, 12.2, 13.3, 14.1, 15.1, 15.2, 16.8, 17.3, 18.0, 18.5, 18.8, 18.9, 19.1, 20.6, 20.9, 21.4, 21.8, 22.3, 22.6, 22.8, 23.1, 23.6, 24.0, 24.5, 24.9, 25.6, 26.8, 27.1, 27.6, 28.1, 28.6, 28.9, 29.2, 30.5, 30.9, 31.7, 32.2, 32.7, 33.1, and 34.0. αCrystalline form XXIII of AP1189 formate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 7.4±0.2, 10.4±0.2, 10.6±0.2, 12.2±0.2, 13.3±0.2, 14.1±0.2, 15.1±0.2, 15.2±0.2, 16.8±0.2, 17.3±0.2, 18.0±0.2, 18.5±0.2, 18.8±0.2, 18.9±0.2, 19.1±0.2, 20.6±0.2, 20.9±0.2, 21.4±0.2, 21.8±0.2, 22.3±0.2, 22.6±0.2, 22.7±0.2, 22.8±0.2, 22.9±0.2, 23.0±0.2, 23.0±0.2, 23.1±0.2, 23.2±0.2, 23.3±0.2, 23.4±0.2, 23.5±0.2, 24.0 ... 0.8±0.2, 23.1±0.2, 23.6±0.2, 24.0±0.2, 24.5±0.2, 24.9±0.2, 25.6±0.2, 26.8±0.2, 27.1±0.2, 27.6±0.2, 28.1±0.2, 28.6±0.2, 28.9±0.2, 29.2±0.2, 30.5±0.2, 30.9±0.2, 31.7±0.2, 32.2±0.2, 32.7±0.2, 33.1±0.2, and 34.0±0.2. α The present disclosure provides crystalline form XXIII of AP1189 formate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXIII of AP1189 formate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K XXIII salt selected from the group consisting of 12.2, 13.3, 15.1, 17.3, 18.9, 20.6, 21.8, 22.8, 23.6, 25.6, 28.9, and 29.2. α Crystalline Form XXIII of AP1189 formate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K αCrystalline Form XXIII of AP1189 formate is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 29. α Crystalline form XXIII of AP1189 formate salt is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0104] AP1189 L-Lactic Acid Forms XXIV The present disclosure provides crystalline form XXIV of AP1189L-lactic acid. Crystalline form XXIV of AP1189L-lactic acid exhibits an XRPD diffractogram as shown in Figure 35. One embodiment of the present disclosure has Cu K at 3.8±0.2, 9.9±0.2, and 11.9±0.2. α Crystalline form XXIV of AP1189L-lactic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 7.7±0.2, 23.0±0.2, and 27.5±0.2. α Crystalline form XXIV of AP1189L-lactic acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 15.4±0.2, 23.9±0.2, and 25.3±0.2. α The present disclosure provides a crystalline form XXIV of AP1189L-lactic acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Crystalline form XXIV of AP1189 L-lactic acid is provided, which exhibits an X-ray pattern (2-theta value) in powder diffraction as measured using radioactive material.

[0105] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.8, 7.7, 9.9, 11.9, 13.6, 14.0, 14.2, 14.7, 15.4, 15.8, 18.0, 18.3, 18.7, 19.3, 19.8, 20.2, 20.4, 20.7, 20.9, 21.4, 21.6, 22.4, 22.6, 23.0, 23.3, 23.7, 23.9, 25.3, 25.9, 27.5, 27.8, 28.5, 28.7, 29.6, 30.0, 30.4, 31.4, 31.8, 33.1, and 33.6. α Crystalline form XXIV of AP1189L-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 3.8±0.2, 7.7±0.2, 9.9±0.2, 11.9±0.2, 13.6±0.2, 14.0±0.2, 14.2±0.2, 14.7±0.2, 15.4±0.2, 15.8±0.2, 18.0±0.2, 18.3±0.2, 18.7±0.2, 19.3±0.2, 19.8±0.2, 20.2±0.2, 20.4±0.2, 20.7±0.2, 20.9±0.2, 21.4±0.2, 21. 6±0.2, 22.4±0.2, 22.6±0.2, 23.0±0.2, 23.3±0.2, 23.7±0.2, 23.9±0.2, 25.3±0.2, 25.9±0.2, 27.5±0.2, 27.8±0.2, 28.5±0.2, 28.7±0.2, 29.6±0.2, 30.0±0.2, 30.4±0.2, 31.4±0.2, 31.8±0.2, 33.1±0.2, and 33.6±0.2. α The present invention provides crystalline form XXIV of AP1189L-lactate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXIV of AP1189L-lactate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XXIV of AP1189L-lactate, which exhibits a Cu K value selected from the group consisting of 3.8, 7.7, 9.9, 11.9, 15.4, 23.0, 23.9, 25.3, and 27.5. αCrystalline form XXIV of AP1189L-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.8±0.2, 7.7±0.2, 9.9±0.2, 11.9±0.2, 15.4±0.2, 23.0±0.2, 23.9±0.2, 25.3±0.2, and 27.5±0.2. α Crystalline form XXIV of AP1189L-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 30. α Crystalline form XXIV of AP1189L-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0106] AP1189DL-Lactic Acid Form XXV The present disclosure provides crystalline form XXV of AP1189DL-lactic acid. Crystalline form XXV of AP1189DL-lactic acid exhibits an XRPD diffractogram as shown in Figure 36. One embodiment of the present disclosure has Cu K at 9.8±0.2, 11.9±0.2, and 27.6±0.2. α Crystalline form XXV of AP1189DL-lactic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 3.8±0.2, 23.3±0.2, and 23.9±0.2. α The present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α The present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. α2 provides crystalline form XXV of AP1189DL-lactic acid, which exhibits an X-ray pattern (2-theta values) in powder diffraction as measured using radioactive material.

[0107] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.8, 7.6, 9.8, 11.9, 13.7, 14.1, 14.3, 15.3, 15.8, 18.2, 18.6, 19.2, 19.8, 20.5, 21.0, 21.3, 21.5, 22.5, 22.7, 22.9, 23.3, 23.6, 23.9, 25.0, 25.6, 26.1, 27.6, 28.7, 29.4, 29.6, 29.8, 30.2, 30.6, 31.6, 32.0, and 34.1. α Crystalline form XXV of AP1189DL-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the disclosure is 3.8±0.2, 7.6±0.2, 9.8±0.2, 11.9±0.2, 13.7±0.2, 14.1±0.2, 14.3±0.2, 15.3±0.2, 15.8±0.2, 18.2±0.2, 18.6±0.2, 19.2±0.2, 19.8±0.2, 20.5±0.2, 21.0±0.2, 21.3±0.2, 21.5±0.2, 22.5±0.2, 22. 7±0.2, 22.9±0.2, 23.3±0.2, 23.6±0.2, 23.9±0.2, 25.0±0.2, 25.6±0.2, 26.1±0.2, 27.6±0.2, 28.7±0.2, 29.4±0.2, 29.6±0.2, 29.8±0.2, 30.2±0.2, 30.6±0.2, 31.6±0.2, 32.0±0.2, and 34.1±0.2. α The present invention provides a crystalline form XXV of AP1189DL-lactate, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify the crystalline form XXV of AP1189DL-lactate by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a crystalline form XXV of AP1189DL-lactate, which exhibits a Cu K value selected from the group consisting of 3.8, 7.6, 9.8, 11.9, 15.3, 23.3, 23.9, 25.6, and 27.6. αThe present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.8±0.2, 7.6±0.2, 9.8±0.2, 11.9±0.2, 15.3±0.2, 23.3±0.2, 23.9±0.2, 25.6±0.2, and 27.6±0.2. α Crystalline form XXV of AP1189DL-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 31. α Crystalline form XXV of AP1189DL-lactic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0108] AP1189 Glutaric Acid Forms XXVI The present disclosure provides crystalline form XXVI of AP1189 glutaric acid. The crystalline form XXVI of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in Figure 37. One embodiment of the present disclosure has Cu K at 8.3±0.2, 15.9±0.2, and 21.9±0.2. α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 12.8±0.2, 15.1±0.2, and 27.1±0.2. α Crystalline form XXVI of AP1189 glutaric acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 3.2±0.2, 8.7±0.2, 14.4±0.2, 16.2±0.2, 19.0±0.2, 19.8±0.2, 28.8±0.2, and 29.5±0.2. α The present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material.α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits an X-ray pattern (2 theta value) in powder diffraction when measured using radioactivity.

[0109] One embodiment of the present disclosure is a Cu K selected from the group consisting of 3.2, 6.3, 8.3, 8.7, 9.8, 10.1, 10.5, 12.8, 13.6, 14.4, 15.1, 15.9, 16.2, 17.1, 17.5, 18.0, 18.3, 19.0, 19.8, 20.2, 20.5, 21.0, 21.4, 21.7, 21.9, 23.0, 23.6, 24.1, 24.5, 25.0, 26.0, 26.5, 27.1, 27.6, 28.2, 28.8, 29.5, 30.6, 31.4, 32.3, and 33.8. α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 3.2±0.2, 6.3±0.2, 8.3±0.2, 8.7±0.2, 9.8±0.2, 10.1±0.2, 10.5±0.2, 12.8±0.2, 13.6±0.2, 14.4±0.2, 15.1±0.2, 15.9±0.2, 16.2±0.2, 17.1±0.2, 17.5±0.2, 18.0±0.2, 18.3±0.2, 19.0±0.2, 19.8±0.2, 20.2±0.2, 20.5±0.2, Cu K selected from the group consisting of 21.0±0.2, 21.4±0.2, 21.7±0.2, 21.9±0.2, 23.0±0.2, 23.6±0.2, 24.1±0.2, 24.5±0.2, 25.0±0.2, 26.0±0.2, 26.5±0.2, 27.1±0.2, 27.6±0.2, 28.2±0.2, 28.8±0.2, 29.5±0.2, 30.6±0.2, 31.4±0.2, 32.3±0.2, and 33.8±0.2. αThe present invention provides crystalline form XXVI of AP1189 glutaric acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXVI of AP1189 glutaric acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 32. α Crystalline form XXVI of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0110] AP1189 Glutaric Acid Forms XXVII The present disclosure provides crystalline form XXVII of AP1189 glutaric acid. The crystalline form XXVII of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in Figure 38. One embodiment of the present disclosure has Cu K at 14.1±0.2, 21.7±0.2, and 25.0±0.2. αCrystalline form XXVII of AP1189 glutaric acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 16.9±0.2, 25.6±0.2, 27.1±0.2, 28.2±0.2, and 28.7±0.2. α Crystalline form XXVII of AP1189 glutaric acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 6.3±0.2, 10.1±0.2, 14.3±0.2, 14.7±0.2, 15.1±0.2, 17.4±0.2, 21.1±0.2, 22.6±0.2, and 26.5±0.2. α The present disclosure provides a crystalline form XXVII of AP1189 glutaric acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Provided is crystalline form XXVII of AP1189 glutaric acid, which exhibits an X-ray pattern (2 theta values) in powder diffraction when measured using radioactivity.

[0111] One embodiment of the present disclosure is 6.3, 10.1, 10.8, 12.6, 12.7, 13.5, 14.1, 14.3, 14.7, 15.1, 15.3, 15.7, 16.5, 16.7, 16.9, 17.4, 18.0, 18.3, 18.7, 18.9, 19.3, 19.6, 20.1, 20.2, 20.5, 20.6, 20.8, 20.9, 21.1, 21.2, 21.3, 21.4, 21.5, 21.6, 21.7, 21.8, 21.9, 22.1, 22.2, 22.3, 22.4, 22.5, 22.6, 22.7, 22.8, 22.9, 23.0, 23.1, 23.2, 23.3, 23.4, 23.5, 23.6, 23.7, 23.8, 23.9, 24.0, 24.1, 24.2, 24.3, 24.4, 24.5, 24.6, 24.7, 25.0, 25.1, 25.3, 25.4, 25.5, 25.6, 25.7, 25.8, 25.9, 26.0, 26.1, 26.2, 26.3, 26.4, 26.5, 26.6, 26.7, 26.9, 27.0, 27.1, Cu K selected from the group consisting of 21.9, 21.3, 21.7, 22.1, 22.6, 23.2, 24.0, 24.4, 25.0, 25.6, 26.0, 26.5, 26.8, 27.1, 27.6, 28.2, 28.7, 29.0, 29.4, 29.7, 30.5, 31.3, 32.0, 33.0, and 34.1 αCrystalline form XXVII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity. One embodiment of the present disclosure is 6.3±0.2, 10.1±0.2, 10.8±0.2, 12.6±0.2, 12.7±0.2, 13.5±0.2, 14.1±0.2, 14.3±0.2, 14.7±0.2, 15.1±0.2, 15.3±0.2, 15.7±0.2, 16.5±0.2, 16.7±0.2, 16.9±0.2, 17.4±0.2, 18.0±0.2, 18.3±0.2, 18.7±0.2, 18.9±0.2, 19.3±0.2, 19.6±0.2, 20.1±0.2, 20.2±0.2, 20.5±0.2, 20.7±0.2, 20.8±0.2, 20.9±0.2, 20.1±0.2, 20.2±0.2, 20.3±0.2, 20.4±0.2, 20.5±0.2, 20.6±0.2, 20.7±0.2, 20.8±0.2, 20.9 ... 0.9±0.2, 21.3±0.2, 21.7±0.2, 22.1±0.2, 22.6±0.2, 23.2±0.2, 24.0±0.2, 24.4±0.2, 25.0±0.2, 25.6±0.2, 26.0±0.2, 26.5±0.2, 26.8±0.2, 27.1±0.2, 27.6±0.2, 28.2±0.2, 28.7±0.2, 29.0±0.2, 29.4±0.2, 29.7±0.2, 30.5±0.2, 31.3±0.2, 32.0±0.2, 33.0±0.2, and 34.1±0.2. α The present invention provides crystalline form XXVII of AP1189 glutaric acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXVII of AP1189 glutaric acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K αCrystalline form XXVII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form XXVII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 33. α Crystalline form XXVII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0112] AP1189 Glutaric Acid Forms XXVIII The present disclosure provides crystalline form XXVIII of AP1189 glutaric acid. The crystalline form XXVIII of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in Figure 91. One embodiment of the present disclosure has Cu K at 14.2±0.2, 16.9±0.2, and 24.5±0.2. α Crystalline form XXVIII of AP1189 glutaric acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 6.3±0.2, 15.2±0.2, 20.9±0.2, and 21.9±0.2. α Crystalline form XXVIII of AP1189 glutaric acid is provided, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 8.9±0.2, 10.1±0.2, 12.6±0.2, 17.4±0.2, 19.1±0.2, 20.6±0.2, and 28.4±0.2. αThe present disclosure provides a crystalline form XXVIII of AP1189 glutaric acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. α Crystalline form XXVIII of AP1189 glutaric acid is provided, which exhibits an X-ray pattern (2 theta value) in powder diffraction when measured using radioactivity.

[0113] One embodiment of the present disclosure is a Cu K selected from the group consisting of 6.3, 8.9, 10.1, 10.4, 10.7, 12.6, 13.4, 13.8, 14.2, 15.2, 15.6, 16.5, 16.9, 17.4, 18.2, 19.1, 19.8, 20.2, 20.6, 20.9, 21.7, 21.9, 22.5, 23.0, 23.6, 23.8, 24.5, 24.9, 25.3, 26.1, 27.2, 27.8, 28.4, 29.3, 29.6, 30.5, 31.0, 31.4, 32.4, 33.6, and 34.3. α Crystalline form XXVIII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 6.3±0.2, 8.9±0.2, 10.1±0.2, 10.4±0.2, 10.7±0.2, 12.6±0.2, 13.4±0.2, 13.8±0.2, 14.2±0.2, 15.2±0.2, 15.6±0.2, 16.5±0.2, 16.9±0.2, 17.4±0.2, 18.2±0.2, 19.1±0.2, 19.8±0.2, 20.2±0.2, 20.6±0.2, 20.9±0.2, 21.7±0. 2, 21.9±0.2, 22.5±0.2, 23.0±0.2, 23.6±0.2, 23.8±0.2, 24.5±0.2, 24.9±0.2, 25.3±0.2, 26.1±0.2, 27.2±0.2, 27.8±0.2, 28.4±0.2, 29.3±0.2, 29.6±0.2, 30.5±0.2, 31.0±0.2, 31.4±0.2, 32.4±0.2, 33.6±0.2, and 34.3±0.2. αThe present invention provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXVIII of AP1189 glutaric acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2 ... α Crystalline form XXVIII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α The present disclosure provides a crystalline form XXVIII of AP1189 glutaric acid, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 34. α Crystalline form XXVIII of AP1189 glutaric acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0114] AP1189 Adipic acid forms XXIX The present disclosure provides crystalline form XXIX of AP1189 adipic acid. The crystalline form XXIX of AP1189 adipic acid exhibits an XRPD diffractogram as shown in Figure 39. One embodiment of the present disclosure has Cu K at 13.4±0.2, 14.5±0.2, and 25.5±0.2. αCrystalline form XXIX of AP1189 adipic acid is provided, which exhibits at least an X-ray line (2-theta value) in a powder diffraction pattern when measured using radioactive material. One embodiment has a Cu K value selected from the group consisting of 17.6±0.2, 23.5±0.2, 25.4±0.2, and 27.1±0.2. α The present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K value selected from the group consisting of 5.2±0.2, 19.2±0.2, and 21.4±0.2. α The present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which further exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive material. α Provided is crystalline form XXIX of AP1189 adipic acid, which exhibits an X-ray pattern (2-theta value) in powder diffraction when measured using radioactive material.

[0115] One embodiment of the present disclosure is a Cu K selected from the group consisting of 5.2, 10.5, 11.2, 12.7, 13.4, 14.5, 15.3, 15.8, 17.1, 17.6, 18.0, 18.8, 19.2, 20.5, 21.0, 21.4, 22.4, 22.8, 23.0, 23.5, 23.9, 24.4, 24.8, 25.4, 25.5, 26.1, 26.3, 27.1, 27.5, 28.1, 28.9, 29.5, 30.6, 32.2, 33.9, and 34.5. αCrystalline form XXIX of AP1189 adipic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive materials. One embodiment of the present disclosure is 5.2±0.2, 10.5±0.2, 11.2±0.2, 12.7±0.2, 13.4±0.2, 14.5±0.2, 15.3±0.2, 15.8±0.2, 17.1±0.2, 17.6±0.2, 18.0±0.2, 18.8±0.2, 19.2±0.2, 20.5±0.2, 21.0±0.2, 21. 4±0.2, 22.4±0.2, 22.8±0.2, 23.0±0.2, 23.5±0.2, 23.9±0.2, 24.4±0.2, 24.8, 25.4, 25.5, 26.1, 26.3, 27.1, 27.5, 28.1, 28.9, 29.5, 30.6, 32.2, 33.9, and 34.5±0.2. α The present disclosure provides crystalline form XXIX of AP1189 adipic acid, which exhibits one or more X-ray lines (2-theta values) in the powder diffraction pattern when measured using radioactive materials. It may be advantageous to identify crystalline form XXIX of AP1189 adipic acid by X-ray lines (2-theta values) with high relative intensity and / or by characteristic X-ray lines. Thus, one embodiment of the present disclosure provides a Cu K 2+ 2-line XXIX having ... α Crystalline Form XXIX of AP1189 adipic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K α Crystalline form XXIX of AP1189 adipic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactive material. One embodiment of the present disclosure provides a Cu K 2-theta value selected from the group consisting of the values ​​listed in Table 35. αCrystalline form XXIX of AP1189 adipic acid is provided, which exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using radioactivity.

[0116] Further characterization of crystal morphology The salts of AP1189 provided herein may be further characterized by the onset temperature they exhibit as assessed by differential scanning calorimetry.

[0117] An embodiment of the present disclosure provides a crystalline form A of AP1189 acetate, which exhibits an onset temperature in differential scanning calorimetry between 185-199°C. A specific embodiment of the present disclosure provides a crystalline form A of AP1189 acetate, which exhibits an onset temperature in differential scanning calorimetry of substantially 192°C. In a further embodiment, the onset temperature is evaluated using a heating rate of 10°C / min. An embodiment of the present disclosure provides a crystalline form A of AP1189 acetate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in Figure 8. An embodiment of the present disclosure provides a crystalline form A of AP1189 acetate, which exhibits a differential scanning calorimetry thermogram according to Figure 8. An embodiment of the present disclosure provides a crystalline form A of AP1189 acetate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 192±7°C, such as 192±6°C, for example 192±5°C, such as 192±4°C, for example 192±3°C, such as 192±2°C, for example 192±1°C.

[0118] An embodiment of the present disclosure provides a crystalline form B of AP1189 succinate that exhibits an onset temperature between 187 and 201° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form B of AP1189 succinate that exhibits an onset temperature of substantially 194° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form B of AP1189 succinate that exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 13. An embodiment of the present disclosure provides a crystalline form B of AP1189 succinate that exhibits a differential scanning calorimetry thermogram according to FIG. 13. An embodiment of the present disclosure provides a crystalline form B of AP1189 succinate, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 195±7°C, such as 195±6°C, for example 195±5°C, such as 195±4°C, for example 195±3°C, such as 195±2°C, for example 195±1°C.

[0119] An embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate, which exhibits an onset temperature in differential scanning calorimetry between 227-241° C. A specific embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate, which exhibits an onset temperature in differential scanning calorimetry of substantially 234° C. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 11. An embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 11. An embodiment of the present disclosure provides a crystalline form C of AP1189 tosylate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 234±7°C, such as 234±6°C, for example 234±5°C, such as 234±4°C, for example 234±3°C, such as 234±2°C, for example 234±1°C.

[0120] An embodiment of the present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits an onset temperature between 208-222° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits an onset temperature of substantially 215° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 12. An embodiment of the present disclosure provides a crystalline form D of AP1189 fumarate, which exhibits a differential scanning calorimetry thermogram according to FIG. 12. An embodiment of the present disclosure provides a crystalline form D of AP1189 fumarate salt which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 215±7°C, such as 215±6°C, for example 215±5°C, such as 215±4°C, for example 215±3°C, such as 215±2°C, for example 215±1°C.

[0121] Certain salts disclosed herein exhibit more than one onset temperature, for example two onset temperatures. The salts may be characterized by either their onset temperature alone or as a combination of onset temperatures.

[0122] An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature between 80-94° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature of substantially 87° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 40. An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 40. One embodiment of the present disclosure provides crystalline Form III of AP1189 napadisylate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 87±7°C, such as 87±6°C, for example 87±5°C, such as 87±4°C, for example 87±3°C, such as 87±2°C, for example 87±1°C.

[0123] An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature between 180-194° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature of substantially 187° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 40. An embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 40. An embodiment of the present disclosure provides crystalline Form III of AP1189 napadisylate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 187±7°C, such as 187±6°C, for example 187±5°C, such as 187±4°C, for example 187±3°C, such as 187±2°C, for example 187±1°C.

[0124] One embodiment of the present disclosure provides crystalline form IV of AP1189 napadisylate, which exhibits a differential scanning calorimetry onset temperature as shown in the examples herein, in particular in Example 4, and / or in the figures herein, in particular in Figure 81. One embodiment of the present disclosure provides crystalline form IV of AP1189 napadisylate, which exhibits a differential scanning calorimetry thermogram according to Figure 81.

[0125] An embodiment of the present disclosure provides crystalline form V of AP1189 esylate, which exhibits an onset temperature between 200-214° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form V of AP1189 esylate, which exhibits an onset temperature of substantially 207° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form V of AP1189 esylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 41. An embodiment of the present disclosure provides crystalline form V of AP1189 esylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 41. An embodiment of the present disclosure provides a crystalline form V of AP1189 esylate salt which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 207±7°C, such as 207±6°C, for example 207±5°C, such as 207±4°C, for example 207±3°C, such as 207±2°C, for example 207±1°C.

[0126] An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate, which exhibits an onset temperature between 71-85° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate, which exhibits an onset temperature of substantially 78° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 82. An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 82. An embodiment of the present disclosure provides crystalline Form VI of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 78±7°C, such as 78±6°C, for example 78±5°C, such as 78±4°C, for example 78±3°C, such as 78±2°C, for example 78±1°C.

[0127] An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate salt, which exhibits an onset temperature between 144-158° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate salt, which exhibits an onset temperature of substantially 151° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 82. An embodiment of the present disclosure provides crystalline form VI of AP1189 edisylate salt, which exhibits a differential scanning calorimetry thermogram according to FIG. 82. An embodiment of the present disclosure provides crystalline Form VI of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 151±7°C, such as 151±6°C, for example 151±5°C, such as 151±4°C, for example 151±3°C, such as 151±2°C, for example 151±1°C.

[0128] An embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate, which exhibits an onset temperature between 218-232° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate, which exhibits an onset temperature of substantially 225° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 42. An embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 42. An embodiment of the present disclosure provides crystalline Form VII of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 225±7°C, such as 225±6°C, for example 225±5°C, such as 225±4°C, for example 225±3°C, such as 225±2°C, for example 225±1°C.

[0129] An embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, which exhibits an onset temperature between 201-215° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, which exhibits an onset temperature of substantially 208° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 43. An embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, which exhibits a differential scanning calorimetry thermogram according to FIG. 43. An embodiment of the present disclosure provides crystalline Form VIII of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 208±7°C, such as 208±6°C, for example 208±5°C, such as 208±4°C, for example 208±3°C, such as 208±2°C, for example 208±1°C.

[0130] An embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits an onset temperature between 52-66° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits an onset temperature of substantially 59° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 44. An embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits a differential scanning calorimetry thermogram according to FIG. 44. An embodiment of the present disclosure provides crystalline Form IX of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 59±7°C, such as 59±6°C, for example 59±5°C, such as 59±4°C, for example 59±3°C, such as 59±2°C, for example 59±1°C.

[0131] An embodiment of the present disclosure provides crystalline form XI of AP1189 edisylate salt, which exhibits an onset temperature between 144-158° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits an onset temperature of substantially 151° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 44. An embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, which exhibits a differential scanning calorimetry thermogram according to FIG. 44. An embodiment of the present disclosure provides crystalline Form IX of AP1189 edisylate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 151±7°C, such as 151±6°C, for example 151±5°C, such as 151±4°C, for example 151±3°C, such as 151±2°C, for example 151±1°C.

[0132] An embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate, which exhibits an onset temperature between 172-186° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate, which exhibits an onset temperature of substantially 179° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 45. An embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate, which exhibits a differential scanning calorimetry thermogram according to FIG. 45. One embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 179±7°C, such as 179±6°C, for example 179±5°C, such as 179±4°C, for example 179±3°C, such as 179±2°C, for example 179±1°C.

[0133] An embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate, which exhibits an onset temperature between 123-137° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate, which exhibits an onset temperature of substantially 130° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 46. An embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate, which exhibits a differential scanning calorimetry thermogram according to FIG. 46. One embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 130±7°C, such as 130±6°C, for example 130±5°C, such as 130±4°C, for example 130±3°C, such as 130±2°C, for example 130±1°C.

[0134] An embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate, which exhibits an onset temperature between 131-145° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate, which exhibits an onset temperature of substantially 138° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 47. An embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate, which exhibits a differential scanning calorimetry thermogram according to FIG. 47. One embodiment of the disclosure provides crystalline Form XII of AP1189 cyclamate, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 138±7°C, such as 138±6°C, for example 138±5°C, such as 138±4°C, for example 138±3°C, such as 138±2°C, for example 138±1°C.

[0135] An embodiment of the present disclosure provides a crystalline form XIII of AP1189 cyclamate, which exhibits an onset temperature between 134-148° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XIII of AP1189 cyclamate, which exhibits an onset temperature of substantially 141° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XIII of AP1189 cyclamate, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or the Figures herein, specifically FIG. 83. An embodiment of the present disclosure provides a crystalline form XIII of AP1189 cyclamate, which exhibits a differential scanning calorimetry thermogram according to FIG. 83. One embodiment of the present disclosure provides crystalline Form XIII of AP1189 cyclamate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 141±7°C, such as 141±6°C, for example 141±5°C, such as 141±4°C, for example 141±3°C, such as 141±2°C, for example 141±1°C.

[0136] An embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate, which exhibits an onset temperature between 219-223° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate, which exhibits an onset temperature of substantially 216° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 48. An embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate, which exhibits a differential scanning calorimetry thermogram according to FIG. 48. An embodiment of the present disclosure provides crystalline Form XIV of AP1189 besylate which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 216±7°C, such as 216±6°C, for example 216±5°C, such as 216±4°C, for example 216±3°C, such as 216±2°C, for example 216±1°C.

[0137] An embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate, which exhibits a peak temperature between 204-218°C in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate, which exhibits a peak temperature of substantially 211°C in differential scanning calorimetry. In a further embodiment, the peak temperature is evaluated using a heating rate of 10°C / min. An embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate, which exhibits a peak temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or the Figures herein, specifically FIG. 49. An embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate, which exhibits a differential scanning calorimetry thermogram according to FIG. 49. One embodiment of the present disclosure provides a crystalline form XV of AP1189 oxalate salt which exhibits a peak temperature in differential scanning calorimetry falling within the interval 211±7°C, such as 211±6°C, for example 211±5°C, such as 211±4°C, for example 211±3°C, such as 211±2°C, for example 211±1°C.

[0138] An embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate, which exhibits an onset temperature between 200-214° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate, which exhibits an onset temperature of substantially 207° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or the Figures herein, specifically FIG. 50. An embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate, which exhibits a differential scanning calorimetry thermogram according to FIG. 50. One embodiment of the present disclosure provides crystalline Form XVI of AP1189 oxalate salt, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 207±7°C, such as 207±6°C, for example 207±5°C, such as 207±4°C, for example 207±3°C, such as 207±2°C, for example 207±1°C.

[0139] One embodiment of the present disclosure provides crystalline form XVII of AP1189 oxalate, which exhibits a differential scanning calorimetry onset temperature as shown in the Examples herein, in particular Example 4, and / or in the Figures herein, in particular Figure 51. One embodiment of the present disclosure provides crystalline form XVII of AP1189 oxalate, which exhibits a differential scanning calorimetry thermogram according to Figure 51.

[0140] An embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid, which exhibits an onset temperature between 198-212° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid, which exhibits an onset temperature of substantially 205° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 52. An embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 52. An embodiment of the present disclosure provides crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 205±7° C., such as 205±6° C., for example 205±5° C., such as 205±4° C., for example 205±3° C., such as 205±2° C., for example 205±1° C.

[0141] An embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate, which exhibits an onset temperature between 74-88° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate, which exhibits an onset temperature of substantially 81° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 53. An embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate, which exhibits a differential scanning calorimetry thermogram according to FIG. 53. One embodiment of the present disclosure provides crystalline Form XIX of AP1189 oxoglutarate, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 81±7°C, such as 81±6°C, for example 81±5°C, such as 81±4°C, for example 81±3°C, such as 81±2°C, for example 81±1°C.

[0142] An embodiment of the present disclosure provides a crystalline form XX of AP1189DL-mandelic acid, which exhibits an onset temperature between 103-117°C in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XX of AP1189DL-mandelic acid, which exhibits an onset temperature of substantially 110°C in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10°C / min. An embodiment of the present disclosure provides a crystalline form XX of AP1189DL-mandelic acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 54. An embodiment of the present disclosure provides a crystalline form XX of AP1189DL-mandelic acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 54. One embodiment of the disclosure provides crystalline form XX of AP1189DL-mandelic acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 110±7°C, such as 110±6°C, for example 110±5°C, such as 110±4°C, for example 110±3°C, such as 110±2°C, for example 110±1°C.

[0143] One embodiment of the present disclosure provides crystalline form XXI of AP1189 mandelic acid, which exhibits a differential scanning calorimetry onset temperature as shown in the examples herein, in particular in Example 4, and / or in the figures herein, in particular in Figure 55. One embodiment of the present disclosure provides crystalline form XXI of AP1189 mandelic acid, which exhibits a differential scanning calorimetry thermogram according to Figure 55.

[0144] An embodiment of the present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits an onset temperature between 132-146° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits an onset temperature of substantially 139° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or the Figures herein, specifically FIG. 56. An embodiment of the present disclosure provides a crystalline form XXII of AP1189 hippuric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 56. One embodiment of the present disclosure provides crystalline form XXII of AP1189 hippuric acid which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 139±7°C, such as 139±6°C, for example 139±5°C, such as 139±4°C, for example 139±3°C, such as 139±2°C, for example 139±1°C.

[0145] An embodiment of the present disclosure provides a crystalline form XXIII of AP1189 formate, which exhibits an onset temperature between 162-176° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXIII of AP1189 formate, which exhibits an onset temperature of substantially 169° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XXIII of AP1189 formate, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 84. An embodiment of the present disclosure provides a crystalline form XXIII of AP1189 formate, which exhibits a differential scanning calorimetry thermogram according to FIG. 84. An embodiment of the present disclosure provides crystalline Form XXIII of AP1189 formate salt which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 169±7°C, such as 169±6°C, for example 169±5°C, such as 169±4°C, for example 169±3°C, such as 169±2°C, for example 169±1°C.

[0146] An embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid, which exhibits an onset temperature between 182-196°C in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid, which exhibits an onset temperature of substantially 189°C in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10°C / min. An embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in Figure 85. An embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid, which exhibits a differential scanning calorimetry thermogram according to Figure 85. One embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 189±7°C, such as 189±6°C, for example 189±5°C, such as 189±4°C, for example 189±3°C, such as 189±2°C, for example 189±1°C.

[0147] An embodiment of the present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which exhibits an onset temperature between 191-205°C in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which exhibits an onset temperature of substantially 198°C in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10°C / min. An embodiment of the present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in Figure 86. An embodiment of the present disclosure provides a crystalline form XXV of AP1189DL-lactic acid, which exhibits a differential scanning calorimetry thermogram according to Figure 86. One embodiment of the present disclosure provides crystalline form XXV of AP1189DL-lactic acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 198±7°C, such as 198±6°C, for example 198±5°C, such as 198±4°C, for example 198±3°C, such as 198±2°C, for example 198±1°C.

[0148] An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature between 102-116° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature of substantially 109° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 87. An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 87. An embodiment of the present disclosure provides crystalline form XXVI of AP1189 glutaric acid which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 109±7°C, such as 109±6°C, for example 109±5°C, such as 109±4°C, for example 109±3°C, such as 109±2°C, for example 109±1°C.

[0149] An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature between 153-167° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature of substantially 160° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 87. An embodiment of the present disclosure provides a crystalline form XXVI of AP1189 glutaric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 87. An embodiment of the present disclosure provides crystalline form XXVI of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 160±7°C, such as 160±6°C, for example 160±5°C, such as 160±4°C, for example 160±3°C, such as 160±2°C, for example 160±1°C.

[0150] An embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, which exhibits an onset temperature between 156-170° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, which exhibits an onset temperature of substantially 163° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 88. An embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 88. An embodiment of the present disclosure provides crystalline Form XXVII of AP1189 glutaric acid which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 163±7°C, such as 163±6°C, for example 163±5°C, such as 163±4°C, for example 163±3°C, such as 163±2°C, for example 163±1°C.

[0151] An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature between 138-152° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature of substantially 145° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the examples herein, specifically in Example 4, and / or in the figures herein, specifically in FIG. 89. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 89. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 145±7° C., such as 145±6° C., for example 145±5° C., such as 145±4° C., for example 145±3° C., such as 145±2° C., for example 145±1° C.

[0152] An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature between 153-167° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature of substantially 160° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or in the Figures herein, specifically FIG. 89. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 89. An embodiment of the present disclosure provides crystalline form XXVIII of AP1189 glutaric acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 160±7°C, such as 160±6°C, for example 160±5°C, such as 160±4°C, for example 160±3°C, such as 160±2°C, for example 160±1°C.

[0153] An embodiment of the present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which exhibits an onset temperature between 176-190° C. in differential scanning calorimetry. A specific embodiment of the present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which exhibits an onset temperature of substantially 183° C. in differential scanning calorimetry. In a further embodiment, the onset temperature is evaluated using a heating rate of 10° C. / min. An embodiment of the present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which exhibits an onset temperature in differential scanning calorimetry as shown in the Examples herein, specifically Example 4, and / or the Figures herein, specifically FIG. 90. An embodiment of the present disclosure provides a crystalline form XXIX of AP1189 adipic acid, which exhibits a differential scanning calorimetry thermogram according to FIG. 90. An embodiment of the present disclosure provides crystalline Form XXIX of AP1189 adipic acid, which exhibits an onset temperature in differential scanning calorimetry falling within the interval of 183±7° C., such as 183±6° C., for example 183±5° C., such as 183±4° C., for example 183±3° C., such as 183±2° C., for example 183±1° C.

[0154] The salts of AP1189 disclosed herein may be further characterized by their FT-IR spectra. FT-IR spectra may be obtained as outlined in Example 13. FT-IR is measured in cm -1 The peaks are reported as corresponding to specific wavenumbers, denoted by . While the peaks are given herein with some degree of certainty, the accuracy of FT-IR measurements is typically within ±1, ±2 or ±3 cm. -1 Therefore, any peaks reported herein should be interpreted as being within ±1, ±2 or ±3 cm. -1 should be interpreted as having a precision of

[0155] One embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate having FT-IR shown in Figure 57. One embodiment of the present disclosure provides crystalline form III of AP1189 napadisylate having FT-IR spectrum peaks shown in Table 45.

[0156] One embodiment of the present disclosure provides crystalline form IV of AP1189 napadisylate having FT-IR shown in Figure 58. One embodiment of the present disclosure provides crystalline form IV of AP1189 napadisylate having FT-IR spectrum peaks shown in Table 46.

[0157] One embodiment of the present disclosure provides a crystalline form V of AP1189 esylate having an FT-IR spectrum shown in Figure 59. One embodiment of the present disclosure provides a crystalline form V of AP1189 esylate having an FT-IR spectrum peaks shown in Table 47.

[0158] One embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate salt, having an FT-IR spectrum shown in Figure 60. One embodiment of the present disclosure provides crystalline form VII of AP1189 edisylate salt, having an FT-IR spectrum peak shown in Figure 48.

[0159] One embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, with FT-IR shown in Figure 61. One embodiment of the present disclosure provides crystalline form VIII of AP1189 edisylate salt, with FT-IR spectrum peaks shown in Table 49.

[0160] One embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, with FT-IR shown in Figure 62. One embodiment of the present disclosure provides crystalline form IX of AP1189 edisylate salt, with FT-IR spectrum peaks shown in Table 50.

[0161] One embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate having an FT-IR spectrum shown in Figure 63. One embodiment of the present disclosure provides a crystalline form X of AP1189 nitrate having an FT-IR spectrum peaks shown in Table 51.

[0162] One embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate having an FT-IR spectrum shown in Figure 64. One embodiment of the present disclosure provides crystalline form XI of AP1189 cyclamate having an FT-IR spectrum peaks shown in Table 52.

[0163] One embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate having an FT-IR spectrum shown in Figure 65. One embodiment of the present disclosure provides a crystalline form XII of AP1189 cyclamate having an FT-IR spectrum peaks shown in Table 53.

[0164] One embodiment of the present disclosure provides crystalline form XIII of AP1189 cyclamate having FT-IR shown in Figure 66. One embodiment of the present disclosure provides crystalline form XIII of AP1189 cyclamate having FT-IR spectrum peaks shown in Table 54.

[0165] One embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate having FT-IR shown in Figure 67. One embodiment of the present disclosure provides crystalline form XIV of AP1189 besylate having FT-IR spectrum peaks shown in Table 55.

[0166] One embodiment of the present disclosure provides crystalline form XV of AP1189 oxalate with FT-IR shown in Figure 68. One embodiment of the present disclosure provides crystalline form XV of AP1189 oxalate with FT-IR spectrum peaks shown in Table 56.

[0167] One embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate having FT-IR shown in Figure 69. One embodiment of the present disclosure provides crystalline form XVI of AP1189 oxalate having FT-IR spectrum peaks shown in Table 57.

[0168] One embodiment of the present disclosure provides crystalline form XVII of AP1189 oxalate having FT-IR shown in Figure 70. One embodiment of the present disclosure provides crystalline form XVII of AP1189 oxalate having FT-IR spectrum peaks shown in Table 58.

[0169] One embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid having FT-IR shown in Figure 71. One embodiment of the present disclosure provides crystalline form XVIII of AP1189(+)-camphor-10-sulfonic acid having FT-IR spectrum peaks shown in Table 59.

[0170] One embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate having an FT-IR spectrum shown in Figure 72. One embodiment of the present disclosure provides a crystalline form XIX of AP1189 oxoglutarate having an FT-IR spectrum peaks shown in Table 60.

[0171] One embodiment of the present disclosure provides crystalline form XX of AP1189DL-mandelic acid with FT-IR shown in Figure 73. One embodiment of the present disclosure provides crystalline form XX of AP1189DL-mandelic acid with FT-IR spectrum peaks shown in Table 61.

[0172] One embodiment of the present disclosure provides crystalline form XXI of AP1189DL-mandelic acid, with FT-IR shown in Figure 74. One embodiment of the present disclosure provides crystalline form XXI of AP1189DL-mandelic acid, with FT-IR spectrum peaks shown in Table 62.

[0173] One embodiment of the present disclosure provides crystalline form XXII of AP1189 hippuric acid having FT-IR shown in Figure 75. One embodiment of the present disclosure provides crystalline form XXII of AP1189 hippuric acid having FT-IR spectrum peaks shown in Table 63.

[0174] One embodiment of the present disclosure provides crystalline form XXIII of AP1189 formate having FT-IR shown in Figure 76. One embodiment of the present disclosure provides crystalline form XXIII of AP1189 formate having FT-IR spectrum peaks shown in Table 64.

[0175] One embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid with FT-IR shown in Figure 77. One embodiment of the present disclosure provides crystalline form XXIV of AP1189L-lactic acid with FT-IR spectrum peaks shown in Table 65.

[0176] One embodiment of the present disclosure provides crystalline form XXV of AP1189DL-lactic acid with FT-IR shown in Figure 78. One embodiment of the present disclosure provides crystalline form XXV of AP1189DL-lactic acid with FT-IR spectrum peaks shown in Table 66.

[0177] One embodiment of the present disclosure provides crystalline form XXVI of AP1189 glutaric acid, with FT-IR shown in Figure 79. One embodiment of the present disclosure provides crystalline form XXVI of AP1189 glutaric acid, with FT-IR spectrum peaks shown in Table 67.

[0178] One embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, with FT-IR shown in Figure 80. One embodiment of the present disclosure provides crystalline form XXVII of AP1189 glutaric acid, with FT-IR spectrum peaks shown in Table 68.

[0179] One embodiment of the present disclosure provides a crystalline form A of AP1189 acetate having an IR spectrum shown in FIG.

[0180] Crystal morphology characteristics The present disclosure further provides salts of AP1189 with high solubility. When solubility is discussed in the context of the present disclosure, it should be taken to mean solubility in aqueous solution, preferably. In one embodiment of the present disclosure, the solubility is in an aqueous medium. Specifically, as shown in the examples herein, crystalline form A of AP1189 acetate was found to have high solubility at pH 1.2. Similarly, crystalline form B of AP1189 succinate was found to have high solubility at pH 1.2-1.3. The objective of the present disclosure is to provide salts of AP1189 with high solubility at low pH, as this improves the in vivo uptake of AP1189 after administration to a subject, for example, after oral administration to a subject.

[0181] As shown in the Examples herein, high solubility of AP1189 salts is not a given: for example, both AP1189 tosylate and AP1189 fumarate were found to have low solubility at low pH, e.g., pH 1.2-1.3.

[0182] One embodiment of the present disclosure provides a salt of AP1189 having a solubility at pH 1.2 of at least 10 mM, such as at least 15 mM, such as at least 20 mM, such as at least 25 mM, such as at least 30 mM, such as at least 35 mM.

[0183] One embodiment of the present disclosure provides a crystalline form A of AP1189 acetate having a solubility of at least 100 mM, such as at least 110 mM, such as at least 120 mM at pH 1.2.

[0184] An embodiment of the present disclosure provides a crystalline form B of AP1189 succinate having a solubility of at least 20 mM, such as at least 25 mM, such as at least 30 mM, such as at least 35 mM at pH 1.2.

[0185] The solubility of a compound may be evaluated by adding an excess of the compound to a volume of a solvent such that a portion of the compound does not dissolve, then isolating and measuring the amount of undissolved compound.Alternatively, the solubility of a compound may be evaluated by adding an excess of the compound to a volume of a solvent such that a portion of the compound does not dissolve, then measuring the amount of the compound in solution.The measurement of the amount of the compound in solution may be performed using any suitable method, for example, HPLC, titration, or spectroscopy.

[0186] Method for preparing AP1189 salt Salts of AP1189 may be prepared as disclosed herein.

[0187] One embodiment of the present disclosure provides a method for preparing AP1189 acetate in crystalline form A, the method comprising: i. combining AP1189 and acetic acid in a solvent to form a mixture; ii. isolating crystalline form A of AP1189 acetate from said mixture.

[0188] As used herein, a "mixture" can refer to a solution or slurry of one or more solids in a solvent or mixture of solvents. In one embodiment of the present disclosure, the mixture is a solution in which one or more solutes are substantially completely dissolved. In one embodiment, the mixture is a slurry in which one or more solutes are only partially dissolved, with the remaining portion of the solute or solutes being undissolved.

[0189] One embodiment of the present disclosure provides a method for preparing AP1189 acetate in crystalline form A, the method comprising: i. combining AP1189 and acetic acid in a solvent to form a mixture; ii. isolating crystalline form A of AP1189 acetate from said mixture.

[0190] In one embodiment, the acetate is ammonium acetate or a metal acetate, such as sodium acetate, lithium acetate, magnesium acetate, potassium acetate or calcium acetate.

[0191] In one embodiment, the method further comprises adding an acid, such as an organic acid or a mineral acid, in step i.

[0192] One embodiment of the present disclosure provides a method for preparing AP1189 acetate in crystalline form A, the method comprising: i. mixing AP1189 acetate in a solvent to form a composition; ii. isolating crystalline form A of AP1189 acetate from said composition.

[0193] In one embodiment, such a method is effective to convert an AP1189 acetate that is not of crystalline form A to an AP1189 acetate of crystalline form A.

[0194] As used herein, a "composition" can refer to a solution or slurry of one solid in a solvent or mixture of solvents. In one embodiment of the present disclosure, the composition is a solution in which the solute is substantially completely dissolved. In one embodiment, the composition is a slurry, in which the solute is only partially dissolved and the remaining portion of the solute is not dissolved. The composition may further include one or more other agents or reagents that may be dissolved or only partially dissolved. Such other agents include, but are not limited to, surfactants, detergents, acids, bases, sugars, salts, biomolecules, bioactive agents, and other excipients, such as pharmaceutical excipients.

[0195] The present disclosure also relates to non-solid compositions, such as liquid compositions, gel compositions, pastes, creams, or ointments, prepared from the crystalline forms disclosed herein. One embodiment provides a liquid composition, gel composition, paste, cream, or ointment prepared from the crystalline forms disclosed herein. One specific embodiment provides a liquid composition prepared from the crystalline forms disclosed herein and a solvent. In a specific embodiment, the solvent is aqueous. In one embodiment, the present disclosure provides a method of preparing a liquid composition, gel composition, paste, cream, or ointment, the method comprising mixing the crystalline forms disclosed herein and one or more additional agents. One specific embodiment provides a method of preparing a liquid composition, the method comprising mixing the crystalline forms disclosed herein and a solvent. In a further embodiment, the solvent is aqueous.

[0196] One aspect of the disclosure provides a method for preparing crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate, said method comprising: i. mixing 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal, aminoguanidine or a salt thereof, and acetic acid or a salt thereof in a solvent; ii. isolating crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate from said mixture.

[0197] Any one of the above agents in step i may be generated in situ from a precursor.

[0198] One aspect of the disclosure provides a method for preparing crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate, said method comprising: providing an N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine or an N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt; ii. introducing acetate as a counter ion using ion exchange; and iii. isolating crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium acetate.

[0199] One embodiment of the present disclosure provides a method for preparing AP1189 succinate in crystalline form B, the method comprising: i. combining AP1189 and succinic acid in a solvent to form a mixture; ii. isolating crystalline form B of AP1189 succinate from the mixture.

[0200] One embodiment of the present disclosure provides a method for preparing AP1189 succinate in crystalline form B, the method comprising: i. mixing an AP1189 salt and succinic acid in a solvent to form a mixture; ii. isolating crystalline form B of AP1189 succinate from the mixture.

[0201] One aspect of the present disclosure provides a method for preparing crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate, said method comprising: i. mixing 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal, aminoguanidine or a salt thereof, and succinic acid or a salt thereof in a solvent; ii. isolating crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate from said composition.

[0202] Any one of the above agents in step i may be generated in situ from a precursor.

[0203] One embodiment of the present disclosure provides a method for preparing crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate, said method comprising: providing an N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine or an N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt; ii. introducing succinate as a counter ion using ion exchange; and iii. isolating crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium succinate.

[0204] In one embodiment of the present disclosure, the solvent is a protic solvent or a polar aprotic solvent, hi one embodiment, the solvent is selected from the group consisting of 1,4-dioxane, methanol, ethanol, 1-propanol, 2-propanol, acetone, acetonitrile, anisole, isopropyl acetate, methyl ethyl ketone, water, and ethyl acetate.

[0205] In one embodiment of the present disclosure, the mixture or composition is heated at least once before the isolation step. In one embodiment, the mixture or composition is heated and cooled in cycles before the isolation step. In one embodiment, the mixture or composition is heated and cooled in cycles for up to 72 hours before the isolation step. In one embodiment, the mixture or composition is heated and cooled in cycles for 15 minutes to 72 hours before the isolation step. In one embodiment, one cycle includes heating the mixture or composition to at least a first threshold temperature, maintaining a temperature above said first threshold temperature for a first duration, then cooling the mixture or composition to a temperature below a second threshold temperature, and maintaining a temperature below said second threshold temperature for said second duration. In one embodiment of the present disclosure, the cycle is performed 1 to 200 times. In one embodiment of the present disclosure, the first threshold temperature is 30°C, such as 35°C, such as 40°C, such as 45°C, such as 50°C, such as 55°C, such as 60°C, such as 65°C, such as 70°C, such as 75°C, such as 80°C. In one embodiment of the present disclosure, the second threshold temperature is 30°C, e.g., 25°C, e.g., 20°C, e.g., 15°C, e.g., 10°C, e.g., 7°C, e.g., 5°C. In one embodiment of the present disclosure, the first and / or second duration is 1-2 minutes, e.g., 2-5 minutes, e.g., 5-10 minutes, e.g., 10-20 minutes, e.g., 20-30 minutes, e.g., 30-40 minutes, e.g., 40-50 minutes, e.g., 50-60 minutes, e.g., 1 hour-1.5 hours, e.g., 1.5-2 hours, e.g., 2-3 hours, e.g., 3-4 hours, e.g., 4-5 hours, e.g., 5-6 hours, e.g., 6-7 hours, e.g., 7-8 hours. In one embodiment, the first duration and the second duration are the same. In one embodiment, the first duration and the second duration are different. In one embodiment, the first duration is different or the same for each cycle. In one embodiment, the second duration is different or the same for each cycle.

[0206] In one embodiment, the heating is to about 40°C.

[0207] In one embodiment, the cooling is to about 20°C.

[0208] In one embodiment, the method further comprises adding an anti-solvent to the mixture or composition prior to the isolating step. In one embodiment, the anti-solvent is a non-polar aprotic solvent. In one embodiment, the anti-solvent is selected from the group consisting of tert-butyl methyl ether, THF and acetone, and mixtures comprising tert-butyl methyl ether, THF or acetone. In one embodiment of the present disclosure, the anti-solvent is water.

[0209] Isolation of the crystals may be performed using any suitable means. In one embodiment of the present disclosure, isolation is performed using filtration, centrifugation, and / or evaporation of one or more solvents. In one embodiment, a slow evaporation method is utilized. In one embodiment, a fast evaporation method is utilized. In one embodiment, evaporation is performed using spray drying. In one embodiment, evaporation is performed using fluidized bed drying, freeze drying, vacuum drying, tumble drying, rotary evaporation, and / or thin film evaporation. In one embodiment, drying is performed using conductive (contact) dryers, including tray dryers, rotary cone dryers, tumble dryers, and paddle dryers. In a further embodiment, drying is performed using a carrier gas.

[0210] In one embodiment of the disclosure, one or more pKa values, e.g. at least one pKa, of the acid corresponding to the counterion of the AP1189 salt are approximately equal to or lower than the pKa values ​​of succinic acid and / or acetic acid. As an example, the "acid corresponding to the counterion of the AP1189 fumarate ion" is fumaric acid. The pKa value of acetic acid is 4.756. The pKa value corresponding to the first acid dissociation of succinic acid is 4.2. The pKa value corresponding to the second acid dissociation of succinic acid is 5.6. Thus, in one embodiment, the pKa value of the acid corresponding to the counterion of the AP1189 salt is approximately equal to or lower than 4.756. In another embodiment, the pKa value of the acid corresponding to the counterion of the AP1189 salt is approximately equal to or lower than 4.2 and / or 5.6.

[0211] One embodiment of the present disclosure provides crystalline Form A of AP1189 acetate prepared by the methods disclosed herein.

[0212] One embodiment of the present disclosure provides crystalline form B of AP1189 succinate prepared by the method disclosed herein.

[0213] One embodiment of the present disclosure provides a method for preparing crystalline form A of AP1189 acetate as disclosed herein, wherein the method further comprises adding seed crystals of crystalline form A of AP1189 acetate prior to the isolation step.One embodiment of the present disclosure provides a method for preparing crystalline form B of AP1189 succinate as disclosed herein, wherein the method further comprises adding seed crystals of crystalline form B of AP1189 succinate prior to the isolation step.

[0214] Pharmaceutical Compositions One embodiment of the present disclosure provides a pharmaceutical composition comprising crystalline Form A of AP1189 acetate as disclosed herein and a pharma- ceutically acceptable excipient.

[0215] One embodiment of the present disclosure provides a pharmaceutical composition comprising crystalline form B of AP1189 succinate as disclosed herein and a pharma- ceutically acceptable excipient.

[0216] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form comprising crystalline form A of AP1189 acetate as disclosed herein or crystalline form B of AP1189 succinate as disclosed herein.

[0217] One embodiment provides a pharmaceutical composition as disclosed herein, wherein the pharmaceutical composition is formulated for oral administration, such composition may be in the form of a tablet or capsule.

[0218] One embodiment of the present disclosure provides a method for preparing a pharmaceutical composition comprising mixing crystalline form A of AP1189 acetate and a pharma- ceutically acceptable excipient.

[0219] One embodiment of the present disclosure provides a method for preparing a pharmaceutical composition comprising mixing crystalline form B of AP1189 succinate with a pharma- ceutically acceptable excipient.

[0220] An embodiment of the present disclosure provides crystalline form A of AP1189 acetate, crystalline form B of AP1189 succinate, or a pharmaceutical composition disclosed herein for use in medicine. An embodiment of the present disclosure provides crystalline form A of AP1189 acetate, crystalline form B of AP1189 succinate, or a pharmaceutical composition disclosed herein for use in the treatment of renal diseases such as proteinuria, cardiovascular diseases, arthritic diseases, or viral infections.

[0221] One embodiment of the present disclosure provides a method of treating a disease or disorder in a subject in need thereof, said method comprising administering to a subject in need thereof crystalline form A of AP1189 acetate, crystalline form B of AP1189 succinate, or a pharmaceutical composition disclosed herein. In a further embodiment, the disease or disorder is selected from the list consisting of a renal disease such as proteinuria, a cardiovascular disease, an arthritic disease, or a viral infection.

[0222] One embodiment of the present disclosure provides the use of crystalline form A of AP1189 acetate or crystalline form B of AP1189 succinate, or a pharmaceutical composition disclosed herein, for the manufacture of a medicament for treating a disease or disorder.

[0223] Medical Use One aspect of the present disclosure is to provide a pharmaceutical formulation, e.g., an oral formulation, comprising crystalline form A of AP1189 acetate as disclosed herein or crystalline form B of AP1189 succinate as disclosed herein for use in treating a disease or disorder.

[0224] In some embodiments, the disease or disorder is selected from the group consisting of a renal disease, an arthritic disease, a viral disease or disorder, and a cardiovascular disease and / or atherosclerosis.

[0225] kidney disease One aspect of the present disclosure is to provide a pharmaceutical formulation, such as an oral formulation, pharmaceutical composition, or unit dosage form, according to the present disclosure for use in the treatment or prevention of renal disease.

[0226] Also disclosed is a method of treating or preventing renal disease in a subject in need thereof, wherein the subject is administered a therapeutically effective amount of an oral formulation, pharmaceutical composition, or unit dosage form of the present disclosure.

[0227] Also disclosed is the use of an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the manufacture of a medicament for the treatment or prevention of renal disease.

[0228] In some embodiments of the present disclosure, there is provided an oral formulation, e.g., a solid oral formulation, comprising crystalline form A of AP1189 acetate or crystalline form B of AP1189 succinate as disclosed herein and at least one pharma- ceutically acceptable excipient for use in the treatment or prevention of renal disease.

[0229] In some embodiments, the renal disease is manifested by proteinuria, hi some embodiments, the renal disease is proteinuric renal disease.

[0230] In some embodiments, the renal disease is a glomerular disease.

[0231] In some embodiments, the kidney disease is nephrotic syndrome (glomerular nephropathy).

[0232] In some embodiments, the kidney disease is primary nephrotic syndrome (primary glomerular nephropathy).

[0233] In some embodiments, the primary nephrotic syndrome is membranous glomerulonephritis (MGN) (or membranous nephropathy (MN)).

[0234] In some embodiments, the primary nephrotic syndrome is focal segmental glomerulosclerosis (FSGS).

[0235] In some embodiments, the primary nephrotic syndrome is membranoproliferative glomerulonephritis (MPGN).

[0236] In some embodiments, the membranoproliferative glomerulonephritis (MPGN) is selected from type 1 MPGN and type 2 MPGN.

[0237] In some embodiments, the primary nephrotic syndrome is rapidly progressive glomerulonephritis (RPGN) (crescentic GN).

[0238] In some embodiments, the primary nephrotic syndrome is minimal change disease (MCD).

[0239] In some embodiments, the kidney disease is secondary nephrotic syndrome (secondary glomerular nephropathy).

[0240] In some embodiments, the secondary nephrotic syndrome is caused by an underlying autoimmune disease, an underlying cancer disease, an underlying genetic disease, or an underlying disease selected from the group consisting of systemic lupus erythematosus (SLE), diabetic nephropathy, sarcoidosis, Sjogren's syndrome, amyloidosis, multiple myeloma, vasculitis, cancer, and a genetic disease (e.g., congenital nephrotic syndrome).

[0241] In some embodiments, the secondary nephrotic syndrome is caused by diabetic nephropathy, an infection such as, for example, a urinary tract infection, such as an infection selected from the group consisting of HIV, syphilis, hepatitis, such as hepatitis A, hepatitis B and hepatitis C, post-streptococcal infection, bladder schistosomiasis and Ebola. In some embodiments, the secondary nephrotic syndrome is drug induced.

[0242] In some embodiments, the kidney disease is an inflammatory kidney disease.

[0243] In some embodiments, the kidney disease is glomerulonephritis (GN), hi some embodiments, the glomerulonephritis is selected from the group consisting of IgA nephropathy (Berger's disease), IgM nephropathy, post-infectious glomerulonephritis, and thin basement membrane disease.

[0244] In some embodiments, the renal disease is idiopathic membranous nephropathy (iMN).

[0245] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing idiopathic membranous nephropathy (iMN).

[0246] Arthritic diseases It is an aspect of the present disclosure to provide an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the treatment or prevention of an arthritic disease.

[0247] Also disclosed is a method of treating or preventing an arthritic disease in a subject in need thereof, wherein the subject is administered a therapeutically effective amount of an oral formulation, pharmaceutical composition or unit dosage form of the present disclosure.

[0248] Also disclosed is the use of an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the manufacture of a medicament for the treatment or prevention of an arthritic disease.

[0249] In some embodiments of the present disclosure, there is provided an oral formulation, e.g., a solid oral formulation, comprising crystalline form A of AP1189 acetate or crystalline form B of AP1189 succinate as disclosed herein and at least one pharma- ceutically acceptable excipient for use in the treatment or prevention of arthritic diseases.

[0250] In one embodiment, the arthritic disease is an autoimmune and / or inflammatory disease manifested by inflammation of the joints.

[0251] In one embodiment, the arthritic disease is selected from the group consisting of inflammatory arthritis, degenerative arthritis, metabolic arthritis, reactive arthritis and infectious arthritis.

[0252] In one embodiment, the arthritic disease is inflammatory arthritis.

[0253] In one embodiment, the inflammatory arthritis is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis.

[0254] In one embodiment, the inflammatory arthritis is rheumatoid arthritis (RA).

[0255] In one embodiment, the rheumatoid arthritis is severely active RA (CDAI>22). In one embodiment, the rheumatoid arthritis is RA with a CDAI>22.

[0256] In one embodiment, the rheumatoid arthritis is RA with a DAS28 score above 5.1.

[0257] In one embodiment, the rheumatoid arthritis is juvenile rheumatoid arthritis (JRA).

[0258] In one embodiment, the degenerative arthritis is osteoarthritis.

[0259] In one embodiment, the metabolic arthritis is gouty arthritis.

[0260] In one embodiment, the reactive arthritis and / or infectious arthritis is arthritis associated with infection with one or more of Hepatitis C, Chlamydia, Gonorrhea, Salmonella or Shigella.

[0261] In one embodiment, the arthritic disease is arthritis as part of a systemic inflammatory disease.

[0262] In one embodiment, the present invention relates to a systemic inflammatory disease, for example, arthritis as part of an inflammatory disease selected from the group consisting of systemic lupus erythematosus, mixed connective tissue disease, Still's disease, and polymyalgia rheumatica.

[0263] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing rheumatoid arthritis.

[0264] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure, in combination with MTX (methotrexate), for use in the treatment or prevention of rheumatoid arthritis.

[0265] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure, alone or in combination with MTX (methotrexate), for use in the treatment or prevention of rheumatoid arthritis in patients who have an inadequate response to MTX (e.g., patients who have a reduced response to MTX treatment, e.g., MTX non-responders).

[0266] Viral diseases or disorders It is an aspect of the present disclosure to provide an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the treatment or prevention of a viral disease or disorder.

[0267] Also disclosed is a method of treating or preventing a viral disease or disorder in a subject in need thereof, wherein the subject is administered a therapeutically effective amount of an oral formulation, pharmaceutical composition, or unit dosage form of the present disclosure.

[0268] Also disclosed is the use of an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the manufacture of a medicament for the treatment or prevention of a viral disease or disorder.

[0269] In some embodiments of the present disclosure, there is provided an oral formulation, e.g., a solid oral formulation, comprising a pharma- ceutically acceptable salt of AP1189 disclosed herein, e.g., AP1189 acetate or AP1189 succinate, and at least one pharma- ceutically acceptable excipient, for use in the treatment or prevention of a viral disease or disorder.

[0270] In some embodiments, the viral disease or disorder is a symptomatic viral disease or disorder.

[0271] In some embodiments, the viral disease or disorder is a symptomatic viral disease or disorder associated with inflammation, eg, hyperinflammation.

[0272] In some embodiments, the viral disease or disorder is a symptomatic viral disease or disorder involving inflammation in one or more organs, e.g., hyperinflammation. Inflammation in one or more organs may also be referred to as local inflammation.

[0273] In some embodiments, the one or more organs are selected from the group consisting of lung, respiratory tract, kidney, liver, pancreas, spleen, exocrine glands, endocrine glands, lymph nodes, brain, heart, muscle, bone marrow, skin, skeleton, bladder, reproductive organs including fallopian tubes, eye, ear, vascular system, digestive tract including small intestine, colon, rectum, anal canal, and prostate.

[0274] In some embodiments, the viral disease or disorder is an inflammatory viral disease or disorder.

[0275] In some embodiments, the viral disease or disorder is a viral respiratory infection, such as a viral lower respiratory tract infection.

[0276] In some embodiments, the viral disease or disorder is a viral respiratory disease or disorder.

[0277] In some embodiments, the viral disease or disorder is a pulmonary viral disease or disorder.

[0278] In some embodiments, the viral disease or disorder is a viral disease or disorder involving inflammation in the respiratory system, for example in the lungs and / or airways.

[0279] In some embodiments, the viral disease or disorder is a viral disease or disorder associated with one or more respiratory symptoms, hi one embodiment, the one or more respiratory symptoms are selected from the group consisting of cough, dry cough, dyspnea, impaired oxygen supply, respiratory disease, respiratory insufficiency, respiratory failure, respiratory syndrome, and acute respiratory disease (ARD).

[0280] In some embodiments, the viral disease or disorder is severe disease, manifested by difficulty breathing, increased respiratory rate, decreased blood oxygen saturation, and / or pulmonary infiltrates.

[0281] In some embodiments, the viral disease or disorder is critical illness manifested by respiratory failure, septic shock, and / or multiple organ dysfunction (MOD) or multiple organ failure (MOF).

[0282] In some embodiments, the viral disease or disorder is viral pneumonia.

[0283] In some embodiments, the viral disease or disorder is viral bronchiolitis.

[0284] In some embodiments, the viral disease or disorder is a viral disease or disorder associated with respiratory failure.

[0285] In some embodiments, the viral disease or disorder is acute respiratory distress syndrome (ARDS).

[0286] In some embodiments, the viral disease or disorder is viral acute respiratory distress syndrome (ARDS).

[0287] In some embodiments, the viral disease or disorder is symptomatic COVID-19 accompanied by acute respiratory distress syndrome (ARDS).

[0288] In some embodiments, there is provided an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing ARDS, e.g., viral ARDS.

[0289] In some embodiments, the viral disease or disorder is systemic inflammatory distress syndrome (SIDS) and / or viral diseases and disorders associated with sepsis.

[0290] In some embodiments, the viral disease or disorder is a viral disease or disorder associated with pulmonary dysfunction.

[0291] In some embodiments, the viral disease or disorder is a viral disease or disorder associated with cytokine release syndrome (CRS) and / or cytokine storm (hypercytokinemia).

[0292] In some embodiments, the viral disease or disorder is caused by a viral infection selected from the group consisting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often referred to as COVID-19 virus; SARS-CoV, MERS-CoV, dengue virus, and influenza virus (including types A, B, and C).

[0293] Cardiovascular disease and / or atherosclerosis It is an aspect of the present disclosure to provide an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the treatment or prevention of cardiovascular disease or atherosclerosis.

[0294] Also disclosed is a method of treating or preventing cardiovascular disease or atherosclerosis in a subject in need thereof, wherein the subject is administered a therapeutically effective amount of an oral formulation, pharmaceutical composition or unit dosage form of the present disclosure.

[0295] Also disclosed is the use of an oral formulation, pharmaceutical composition or unit dosage form according to the present disclosure for use in the manufacture of a medicament for the treatment or prevention of cardiovascular disease and / or atherosclerosis.

[0296] In some embodiments of the present disclosure, there is provided an oral formulation, e.g., a solid oral formulation, comprising crystalline form A of AP1189 acetate as disclosed herein or crystalline form B of AP1189 succinate as disclosed herein and at least one pharma- ceutically acceptable excipient as disclosed herein for use in the treatment or prevention of cardiovascular disease and / or atherosclerosis.

[0297] In some embodiments, the cardiovascular disease is selected from the group consisting of coronary artery disease (CAD), such as angina and myocardial infarction (commonly known as heart attack); stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathies, cardiac rhythm disorders, congenital heart disease, valvular heart disease, carditis, aortic aneurysm, peripheral arterial disease, vascular disease, thromboembolic disease, and venous thrombosis.

[0298] In some embodiments, the cardiovascular disease is atherosclerotic cardiovascular disease.

[0299] In some embodiments, the atherosclerotic cardiovascular disease is selected from the group consisting of coronary artery disease, stroke (cerebrovascular disease), and peripheral artery disease.

[0300] In some embodiments, the cardiovascular disease is vascular inflammation.

[0301] systemic inflammatory diseases An aspect of the present disclosure is to provide an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing a systemic inflammatory disease.

[0302] Also disclosed is a method of treating or preventing a systemic inflammatory disease in a subject in need thereof, wherein the subject is administered a therapeutically effective amount of an oral formulation, pharmaceutical composition, or unit dosage form of the present disclosure.

[0303] Also disclosed is the use of an oral formulation, pharmaceutical composition, or unit dosage form according to the present disclosure for use in the manufacture of a medicament for the treatment or prevention of a systemic inflammatory disease.

[0304] In some embodiments of the present disclosure, there is provided an oral formulation, e.g., a solid oral formulation, comprising crystalline form A of AP1189 acetate or crystalline form B of AP1189 succinate as disclosed herein and at least one pharma- ceutically acceptable excipient as disclosed herein, for use in the treatment or prevention of a systemic inflammatory disease.

[0305] Systemic diseases that can affect the nervous system include a variety of diseases with presumed inflammatory and autoimmune pathomechanisms, such as Behçet's disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögren's syndrome. This group of diseases includes systemic inflammatory diseases that involve genetically defined dysregulation of the innate immune system, as well as systemic autoimmune diseases that are characterized by alterations in adaptive immunity such as autoantibodies and autoreactive T cells.

[0306] In some embodiments, the systemic inflammatory disease is an autoimmune disease.

[0307] In some embodiments, the systemic inflammatory disease is selected from the group consisting of Behcet's disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, Sjogren's syndrome, myositis including dermatomyositis and polymyositis, vasculitis, giant cell arteritis, ankylosing spondylitis, polymyalgic rheumatoid arthritis, and psoriatic arthritis. EXAMPLES

[0308] Example 1: Salt formation From the reaction to obtain N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine To a heated slurry or solution of 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal and aminoguanidine or a salt thereof in a protic or polar aprotic solvent, an acid is added as a slurry or solution in a protic or polar aprotic solvent. The resulting mixture is heated and preferably stirred until the reaction is complete, then cooled and optionally an anti-solvent, such as a non-polar aprotic solvent, is added. The resulting salt is isolated by conventional methods such as filtration, centrifugation, evaporation of the solvent, including spray drying.

[0309] From the free base To a slurry of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine in a protic or polar aprotic solvent, an acid (e.g., an excess of said acid) is added as a slurry or solution in a protic or polar aprotic solvent. The resulting mixture is cycled for 15 minutes to 72 hours, then cooled and optionally an anti-solvent, such as a non-polar aprotic solvent, is added. The resulting salt is isolated by conventional methods such as filtration, centrifugation, evaporation of the solvent, including spray drying.

[0310] From another salt This method is feasible if the acid corresponding to the counterion in the salt formed is stronger. To a slurry of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt in a protic or polar aprotic solvent, an excess of acid is added as a slurry or solution in a protic or polar aprotic solvent. The resulting mixture is cycled for 15 minutes to 72 hours, then cooled and optionally an anti-solvent, such as a non-polar aprotic solvent, is added. The resulting salt is isolated by conventional methods such as filtration, centrifugation, or evaporation of the solvent, including spray drying.

[0311] Exemplary Procedure for Formation of Acetate Salts To 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal and aminoguanidine bicarbonate in ethanol was added 0.9 equivalents of acetic acid slowly with stirring. The mixture was heated at reflux for at least 2 hours before adding an additional 0.11 equivalents of acetic acid at 50-55°C for 1 hour. The suspension was cooled to 60°C and then tert-butyl methyl ether was added. The mixture was cooled and maintained at 2-5°C for 10-16 hours. It was filtered, washed with tert-butyl methyl ether, and then recrystallized from ethanol.

[0312] This procedure produces a polymorph of AP1189 acetate corresponding to XRPD pattern 1.

[0313] Exemplary Procedure for the Formation of the Succinate Salt of AP1189 A slurry was prepared by adding 2-propanol:water 90:10 v / v to AP1189 acetate. 2-propanol:water 90:10 v / v was added to 1.1 equivalents of succinic acid. This counterion slurry was added to the acetate slurry. Temperature cycling was performed between ambient and 40°C for approximately 18 hours using a 4 hour hold period at ambient and a 4 hour hold period at 40°C. The entire slurry was then isolated by Buchner filtration and washed with deionized water. The solid was dried under vacuum at ambient temperature.

[0314] This procedure produces a polymorph of AP1189 succinate corresponding to XRPD pattern 1.

[0315] Salt decomposition of free base AP1189 Ethyl acetate and 1M sodium bicarbonate were added to AP1190 acetate to create a biphasic mixture. The mixture was transferred to a separatory funnel and the aqueous phase was removed. The organic phase was washed with water. The organic phase was dried over sodium sulfate. The organic phase solvent was removed by rotary evaporation.

[0316] This procedure produced AP1189 free base as a solid.

[0317] Example 2: Polymorphism assessment for AP1189 acetate method Polymorphism evaluation was performed to identify alternative polymorphs of AP1189 acetate: AP1189 acetate was dissolved in aqueous 1,4-dioxane and lyophilized to obtain an amorphous solid. Aliquots were suspended in selected solvents and heated in temperature cycles between ambient and 40 °C for 3 days, and then isolated by filtration.

[0318] result Table 2 summarizes the results of the polymorphism studies. Acetate Pattern 1 was obtained from eight solvent systems. Mixtures of Patterns 1 and 2 were obtained from eight solvent systems. Pattern 3 was obtained from THF. Extended temperature cycling for an additional 3 days for the mixture of acetate Patterns 1 and 2 obtained from ethyl acetate resulted in conversion to acetate Pattern 1. [Table 2]

[0319] conclusion Polymorphism studies on AP1189 acetate revealed three different polymorphs corresponding to XRPD pattern 1, patterns 1 and 2 (ie, pattern 2 as a mixture with pattern 1), and pattern 3.

[0320] Example 3: X-ray powder diffraction method XRPD analysis was performed on a PANalytical X'pert pro equipped with a PIXcel detector (128 channels) scanning the samples between 3 and 35° 2θ. The materials were gently ground (if necessary) to free aggregates and loaded into a multi-well plate with a polymeric film of Kapton or Mylar to support the samples. The multi-well plate was then placed in the diffractometer and analyzed using Cu K radiation (α1 λ=1.54060 Å; α2=1.54443 Å; β=1.39225 Å; α1:α2 ratio=0.5) running in transmission mode (step width 0.0130° 2θ, step time 18.87 s) using a generator setting of 40 kV / 40 mA.

[0321] result AP1189 Acetate Form A The XRPD diffractogram of AP1189 acetate pattern 1 crystallized from acetonitrile is shown in Figure 1. The corresponding XRPD diffractogram peak list for acetate pattern 1 is shown in Table 3. [Table 3]

[0322] AP1189 Acetate Form I The XRPD diffractograms of AP1189 acetate patterns 1 and 2 crystallized from ethyl acetate are shown in Figure 2. The corresponding XRPD diffractogram peaks for acetate patterns 1 and 2 are listed in Table 4. [Table 4] JPEG2024523459000008.jpg21159

[0323] AP1189 Acetate Form II The XRPD diffractogram of AP1189 acetate pattern 3 crystallized from THF is shown in Figure 3. The corresponding XRPD diffractogram peak list for acetate pattern 3 is shown in Table 5. [Table 5] JPEG2024523459000010.jpg90159

[0324] AP1189 tosylate form C The XRPD diffractogram for AP1189 tosylate salt pattern 1 crystallized from methanol is shown in Figure 4. The corresponding XRPD diffractogram peak list for tosylate salt pattern 1 is shown in Table 6. [Table 6] JPEG2024523459000012.jpg24159

[0325] AP1189 fumarate form D The XRPD diffractogram for AP1189 fumarate salt pattern 1 crystallized from isopropyl alcohol:water 90:10 v / v is shown in Figure 5. The corresponding XRPD diffractogram peaks for fumarate salt pattern 1 from isopropyl alcohol:water 90:10 v / v are listed in Table 7. [Table 7] JPEG2024523459000014.jpg49159

[0326] AP1189 succinate form B The XRPD diffractogram for AP1189 succinate salt pattern 1 crystallized from isopropanol:water 90:10 v / v is shown in Figure 6. The corresponding XRPD diffractogram peaks for succinate salt pattern 1 are listed in Table 8. [Table 8]

[0327] AP1189 napadisylate form III The XRPD diffractogram for AP1189 napadisylate pattern 1 crystallized from 2-propanol:water 90:10% v / v is shown in Figure 14. The corresponding XRPD diffractogram peak list for napadisylate pattern 1 is shown in Table 9. [Table 9]

[0328] AP1189 napadisilate form IV The XRPD diffractogram for AP1189 napadisylate pattern 2 crystallized from THF is shown in Figure 15. The corresponding XRPD diffractogram peak list for napadisylate pattern 2 is shown in Table 10. [Table 10]

[0329] AP1189 esylate form V The XRPD diffractogram for AP1189 esylate salt pattern 1 crystallized from methyl ethyl ketone is shown in Figure 16. The corresponding XRPD diffractogram peak list for esylate salt pattern 1 is shown in Table 11. [Table 11]

[0330] AP1189 edisylate form VI The XRPD diffractogram for AP1189 edisylate salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 17. The corresponding XRPD diffractogram peak list for edisylate salt pattern 1 is shown in Table 12. [Table 12]

[0331] AP1189 edisylate form VII The XRPD diffractogram for AP1189 edisylate salt pattern 2 crystallized from methyl ethyl ketone is shown in Figure 18. The corresponding XRPD diffractogram peak list for edisylate salt pattern 2 is shown in Table 13. [Table 13]

[0332] AP1189 edisylate form VIII The XRPD diffractogram for AP1189 edisylate salt pattern 4 crystallized from THF is shown in Figure 19. The corresponding XRPD diffractogram peak list for edisylate salt pattern 4 is shown in Table 14. [Table 14]

[0333] AP1189 edisylate form IX The XRPD diffractogram for AP1189 edisylate salt pattern 5 crystallized from 2-propanol:water (80:20% v / v) is shown in Figure 20. The corresponding XRPD diffractogram peak list for edisylate salt pattern 5 is shown in Table 15. [Table 15]

[0334] AP1189 Nitrate Form X The XRPD diffractogram for AP1189 nitrate pattern 1 crystallized from THF is shown in Figure 21. The corresponding XRPD diffractogram peaks for nitrate pattern 1 are listed in Table 16. [Table 16]

[0335] AP1189 cyclamate form XI The XRPD diffractogram for AP1189 cyclamate pattern 2 crystallized from THF is shown in Figure 22. The corresponding XRPD diffractogram peaks for cyclamate pattern 2 are listed in Table 17. [Table 17]

[0336] AP1189 cyclamate form XII The XRPD diffractogram for AP1189 cyclamate pattern 4 crystallized from acetone is shown in Figure 23. The corresponding XRPD diffractogram peaks for cyclamate pattern 4 are listed in Table 18. [Table 18]

[0337] AP1189 cyclamate form XIII The XRPD diffractogram for AP1189 cyclamate pattern 5 crystallized from THF is shown in Figure 24. The corresponding XRPD diffractogram peaks for cyclamate pattern 5 are listed in Table 19. [Table 19] JPEG2024523459000027.jpg37159

[0338] AP1189 besylate form XIV The XRPD diffractogram for AP1189 besylate salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 25. The corresponding XRPD diffractogram peak list for besylate salt pattern 1 is shown in Table 20. [Table 20]

[0339] AP1189 oxalate form XV The XRPD diffractogram for AP1189 oxalate salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 26. The corresponding XRPD diffractogram peaks for oxalate salt pattern 1 are listed in Table 21. [Table 21]

[0340] AP1189 oxalate form XVI The XRPD diffractogram for AP1189 oxalate salt Pattern 2 crystallized from acetone is shown in Figure 27. The corresponding XRPD diffractogram peak list for oxalate salt Pattern 2 is shown in Table 22. [Table 22]

[0341] AP1189 oxalate form XVII The XRPD diffractogram for AP1189 oxalate salt Pattern 4 crystallized from THF is shown in Figure 28. The corresponding XRPD diffractogram peak list for oxalate salt Pattern 4 is shown in Table 23. [Table 23] JPEG2024523459000032.jpg14159

[0342] AP1189 (+)-Camphor-10-sulfonic acid form XVIII The XRPD diffractogram for AP1189 (+)-camphor-10-sulfonic acid salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 29. The corresponding XRPD diffractogram peaks for (+)-camphor-10-sulfonic acid salt pattern 1 are listed in Table 24. [Table 24]

[0343] AP1189 oxoglutarate form XIX The XRPD diffractogram for AP1189 oxoglutarate pattern 1 crystallized from acetone is shown in Figure 30. The corresponding XRPD diffractogram peaks for oxoglutarate pattern 1 are listed in Table 25. [Table 25]

[0344] AP1189DL-Mandelic acid form XX The XRPD diffractogram for AP1189 DL-mandelic acid salt pattern 2 crystallized from methyl ethyl ketone is shown in Figure 31. The corresponding XRPD diffractogram peaks for DL-mandelic acid salt pattern 2 are listed in Table 26. [Table 26] JPEG2024523459000036.jpg14159

[0345] AP1189DL-Mandelic acid form XXI The XRPD diffractogram for AP1189 DL-Mandelic acid salt pattern 3 crystallized from acetone is shown in Figure 32. The corresponding XRPD diffractogram peaks for DL-Mandelic acid salt pattern 3 are listed in Table 27. [Table 27]

[0346] AP1189 Morphology of Hippuric Acid XXII The XRPD diffractogram for AP1189 hippuric acid salt pattern 1 crystallized from methyl ethyl ketone is shown in Figure 33. The corresponding XRPD diffractogram peaks for hippuric acid salt pattern 1 are listed in Table 28. [Table 28]

[0347] AP1189 formic acid form XXIII The XRPD diffractogram for AP1189 formate salt pattern 1 crystallized from acetone is shown in Figure 34. The corresponding XRPD diffractogram peaks for formate salt pattern 1 are listed in Table 29. [Table 29]

[0348] AP1189 L-Lactic Acid Forms XXIV The XRPD diffractogram for AP1189 L-lactic acid salt pattern 1 crystallized from acetone is shown in Figure 35. The corresponding XRPD diffractogram peaks for L-lactic acid salt pattern 1 are listed in Table 30. [Table 30]

[0349] AP1189DL-Lactic Acid Form XXV The XRPD diffractogram for AP1189 DL-lactic acid salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 36. The corresponding XRPD diffractogram peaks for DL-lactic acid salt pattern 1 are listed in Table 31. [Table 31]

[0350] AP1189 Glutaric Acid Forms XXVI The XRPD diffractogram for AP1189 glutaric acid salt pattern 1 crystallized from acetone is shown in Figure 37. The corresponding XRPD diffractogram peaks for glutaric acid salt pattern 1 are listed in Table 32. [Table 32]

[0351] AP1189 Glutaric Acid Forms XXVII The XRPD diffractogram for AP1189D glutaric acid salt pattern 2 crystallized from methyl ethyl ketone is shown in Figure 38. The corresponding XRPD diffractogram peaks for glutaric acid salt pattern 2 are listed in Table 33. [Table 33] JPEG2024523459000044.jpg36159

[0352] AP1189 Glutaric Acid Forms XXVIII The XRPD diffractogram of AP1189 glutaric acid salt pattern 4 crystallized from acetone is shown in Figure 91. The corresponding XRPD diffractogram peaks of glutaric acid salt pattern 4 are listed in Table 34. [Table 34]

[0353] AP1189 Adipic acid forms XXIX The XRPD diffractogram for AP1189 adipic acid salt pattern 1 crystallized from 2-propanol:water 80:20% v / v is shown in Figure 39. The corresponding XRPD diffractogram peaks for adipic acid salt pattern 1 are listed in Table 35. [Table 35]

[0354] conclusion X-ray powder diffraction data was collected for a selection of different AP1189 salts.

[0355] Example 4: Thermogravimetry / Differential Scanning Calorimetry and Differential Scanning Calorimetry method For TGA / DSC evaluation, approximately 5-10 mg of material was added to a pre-tared open aluminum pan and loaded into a TA Instruments Discovery SDT 650 Auto-Simultaneous DSC and held at room temperature. The sample was then heated from 30°C to 400°C at a rate of 10°C / min while the change in sample weight was recorded along with the heat flow response (DSC). 200 cm was used as the sample purge gas. 3 Nitrogen was used at a flow rate of 1 / min.

[0356] For DSC evaluation, approximately 1-5 mg of material was weighed into an aluminum DSC pan and sealed, but not hermetically sealed, with an aluminum lid. The sample pan was then loaded into a TA Instruments Discovery DSC 2500 Differential Scanning Calorimeter equipped with an RC90 cooler. The sample and reference were heated to 230 or 240 °C at a scan rate of 10 °C / min and the resulting heat flow response was monitored. The samples were recooled to 20 °C and then reheated again to 230 or 240 °C, all at 10 °C / min. 50 cm was used as purge gas. 3 Nitrogen was used at a flow rate of 1 / min.

[0357] result The results of the TGA / DSC evaluation and the DSC evaluation are shown in Table 36. [Table 36] JPEG2024523459000048.jpg96159

[0358] Example 5: Nuclear Magnetic Resonance method NMR experiments were performed on a Bruker AVIIIHD spectrometer equipped with a DCH or PRODIGY cryoprobe operating at 500.12 MHz or 500.23 MHz for protons. Experiments were performed in deuterated DMSO, and each sample was prepared to a concentration of approximately 10 mM.

[0359] result AP1189 from salt 1 The chemical shifts and integrals of the 1 H-NMR signals are shown in Table 37. [Table 37] JPEG2024523459000050.jpg154159

[0360] Further AP1189 salt from 1 The chemical shifts and integrals of the 1 H-NMR signals are reported below as "Relative integral (chemical shift in ppm)".

[0361] AP1189 napadisilate pattern 1:0.9004(11.0566);1(8.8646);0.8869(8.1785);1.0576(7.9423);0.908(7.9008);0.9585(7.801);0.9148(7.7435);0.9532(7.6544);3.6717(7.4436);1.8894(7.4081);0.9671(7.1002);0.929(6.7843);0.9571(6.5594);1.8182(6.364).

[0362] AP1189 napadisilate pattern 2:0.7543(11.0629);2.557(8.8634);1(8.1806);2.6217(7.941);0.974(7.9028);1.0037(7.7975);0.8754(7.739);1.0347(7.656);3.5752(7.4103);0.8399(7.096);0.7845(6.7841);0.7859(6.5499);1.5389(6.3551);2.0976(1.764).

[0363] AP1189 esylate pattern 1:1(11.2407);1.0302(8.1724);1.0864(7.9088);1.1096(7.7985);1.0938(7.7285);1.1564(7.6532);3.1799(7.5066);1.0215(7.0896);1.0396(6.7843);1.0711(6.5428);2.0916(6.3686);2.2641(2.4374);3.2592(1.0734).

[0364] AP1189 edisylate pattern 1:0.9389(11.1051);1(8.1816);1.1764(7.915);1.2168(7.8057);1.0864(7.7419);1.1486(7.66119);4.2764(7.4823);1.1528(7.1064);1.0797(6.7887);1.1652(6.5561);1.941(6.3703);3.1838(2.6499).

[0365] AP1189 edisylate pattern 2:1(8.1754);1.0457(7.9043);1.055(7.7933);1.0496(7.7126);1.0385(7.6399);3.6468(7.2657);1.0648(7.074);1.0135(6.758);1.0489(6.5107);2.0588(6.3692);1.8314(2.6762);0.4358(1.8961).

[0366] AP1189 edisylate pattern 4:0.9704(11.1726);0.3728(8.6189);1(8.1889);1.0879(7.9082);1.1163(7.8048);1.1018(7.7262);1.2479(7.649);3.9613(7.4808);1.239(7.081);1.0035(6.7776);0.9982(6.5529);1.9363(6.364);5.8322(2.7036);0.3181(1.9026);2.3234(1.7578).

[0367] AP1189 edisylate pattern 5:1(11.1488);1.0198(8.1751);1.0482(7.9077);1.0504(7.7991);1.0194(7.7345);1.0616(7.6536);3.4068(7.4789);0.9855(7.0894);1.0035(6.7829);1.0279(6.5554);2.0024(6.3682);2.1727(2.6737).

[0368] AP1189 Nitrate Pattern 1:0.855(11.0579);1(8.1758);1.1992(7.9089);1.1124(7.8009);1.1028(7.7426);1.1063(7.6607);3.1664(7.4236);0.9762(7.0947);0.9159(6.7819);0.9574(6.5523);1.984(6.3525);0.3361(2.0666);0.2449(1.909);0.3598(0.9061).

[0369] AP1189 cyclamate pattern 2: 0.8634(11.3476); 1(8.1712); 1.0915(7.9119); 1.0957(7.7968); 1.0703(7.7201); 1.1419(7.6556); 3.5247(7.5221); 1.0013(7.0879); 1.0173(6.785 6);1.0326(6.5094);2.0216(6.3759);1.0084(2.8695);0.0439(2.0639);2.0563(1.889);2.0597(1.599);1.0453(1.4747);2.129(1.157);3.1001(1.0312);0.0716(0.9069).

[0370] AP1189 cyclamate pattern 4: 0.9437(11.3653);1(8.1707);1.0501(7.9029);1.0542(7.7958);1.0598(7.7205);1.0888(7.6517);3.4746(7.4706);0.9954(7.0905);1.007 2(6.7896);1.0321(6.5128);1.994(6.3726);1.0213(2.877);0.7166(1.909);1.9717(1.8707);2.0065(1.5967);0.9909(1.4832);2.0949(1.1546);3.0111(1.037).

[0371] AP1189 besylate pattern 1:0.8981(11.0474);1(8.1732);1.0646(7.9073);1.077(7.8033);1.0818(7.7354);1.0947(7.6588);2.0107(7.5938);3.1874(7.4508);3.2895(7.3107);1.0376(7.0824);1.0335(6.7775);1.0395(6.5391);2.042(6.3614);0.081(1.9071);0.1755(1.0388).

[0372] AP1189 oxalate pattern 1:1(8.1532);1.0304(7.8871);1.0453(7.7725);1.0065(7.681);1.0478(7.6319);2.9399(7.1515);1.1976(7.0314);1.0234(6.7175);2.04(6.4104);1.014(6.3244);0.105(1.0377).

[0373] AP1189 oxalate pattern 2:1(8.1689);1.0959(7.902);1.0853(7.7878);1.2373(7.7194);1.4553(7.6482);2.6457(7.5415);0.988(7.0686);1.0003(6.7689);2.0665(6.4477);0.9929(6.3465);0.063(2.0968).

[0374] AP1189 oxalate pattern 4:1(8.1515);1.0445(7.8892);1.0462(7.7742);1.0282(7.6758);1.0219(7.6301);2.6642(7.1097);1.2483(7.024);1.0034(6.7159);2.0859(6.3975);0.997(6.3192);0.1217(1.7624).

[0375] AP1189(+)-Camphor-10-sulfonic acid Pattern 1: 0.8814(11.1521);1(8.1744);1.0627(7.9089);1.0996(7.8055);1.0638(7.7356);1.114(7.6573);3.3236(7.4351);1.012(7.0913);1.0191(6.7741);1.0391(6.5267);2 .0264(6.3743);1.0414(2.8818);1.35(2.661);1.381(2.3787);1.0478(2.2319);1.0068(1.9412);0.0876(1.9105);0.9801(1.8546);1.1612(1.7889);2.1252(1.276);3.0996(1.0314);3.0831(0.7379).

[0376] AP1189 oxoglutarate pattern 1:1(8.1669);1.8014(7.8993);1.5121(7.7883);1.1804(7.7205);1.0352(7.6395);0.9369(7.0709);0.9511(6.7756);0.9802(6.5257);1.8945(6.3703);2.0183(2.7771);2.0935(2.3762);3.775(2.0831);0.2799(1.9065).

[0377] AP1189DL-Mandelic acid pattern 2:1(8.1765);1.1357(7.9075);1.1573(7.8014);2.282(7.658);2.4615(7.373);2.4095(7.2395);1.2411(7.1718);1.0362(7.0527);0.9926(6.7419);2.2546(6.4249);0.9906(6.3355);1.1242(4.6566);1.9165(2.4309);2.6899(2.0752);2.7184(0.9137).

[0378] AP1189DL-Mandelic acid pattern 3:1(8.1719);1.0907(7.8985);1.1332(7.7964);2.0988(7.6516);3.1244(7.3791);1.5978(7.3108);2.5396(7.2455);1.2963(7.173);1.0635(7.0434);0.9514(6.7353);2.2616(6.418);0.9986(6.3312);1.0491(4.6436);1.5842(2.0853);0.9834(1.8978);0.3683(0.9089).

[0379] AP1189 Hippuric acid pattern 1: 0.7548(13.5715); 1.1969(8.3963); 1(8.16); 1.0703(7.8863); 2.3929(7.8433); 1.087(7.7812); 1.0158(7.6668); 1.0966(7.633); 1.3863(7.5276); 2.6 135(7.4589);1.2686(7.0294);1.028(6.7102);1.0111(6.4352);0.9644(6.3695);1.0492(6.3181);2.4392(3.7385);0.3539(2.0654);0.4149(1.8873);0.3571(0.9132).

[0380] AP1189 formate pattern 1: 1.0292(8.2978);1(8.1572);1.11(7.8919);1.1402(7.7789);2.0493(7.6393);1.4368(7.0232);1.0484(6.6976);1.0843(6.4271);0.8414(6.3563);1.3615(6.315).

[0381] AP189 L-lactate pattern 1:1(8.1477);1.0199(7.8914);1.0281(7.7688);1.016(7.6355);0.912(7.5871);0.8946(6.9724);0.9739(6.6292);0.9826(6.4603);1.1694(6.2913);2.0197(6.1996);3.1739(1.8746).

[0382] AP1189DL-Lactate pattern 1:1(8.162);1.0734(7.8983);1.089(7.7857);1.1388(7.6686);0.8544(7.6311);3.8862(7.0181);1.0121(6.703);1.8676(6.4245);1.4225(6.3346);1.1312(3.8217);3.4204(1.1735).

[0383] AP1189 glutaric acid pattern 1:1(8.1619);1.2231(7.8898);1.2238(7.7746);2.2688(7.6176);1.1544(6.9851);1.1233(6.6576);2.5919(6.4392);2.628(6.2658);5.0598(2.1953);0.155(2.0861);2.5366(1.6883).

[0384] AP1189 glutaric acid pattern 2:1(8.1501);1.0837(7.8878);1.0944(7.7738);2.0793(7.6257);1.07(6.9923);1.5227(6.6621);1.5132(6.44);2.1718(6.286);4.2751(2.1788);0.1721(1.8732);2.132(1.677);0.0775(0.9072).

[0385] AP1189 glutaric acid pattern 4:1(8.1477);1.0427(7.889);1.0498(7.7725);2.067(7.6188);1.0236(6.9887);1.0425(6.6531);4.4525(6.4277);2.3299(6.2728);4.2147(2.1823);2.0993(1.6841).

[0386] AP1189 Adipic acid pattern 1:1(8.1534);1.0731(7.889);1.1078(7.7765);2.1422(7.6374);1.3346(7.0193);1.1785(6.6987);1.078(6.4364);2.1349(6.3344);0.3194(3.7674);6.2668(2.1336);1.1285(1.8523);6.2972(1.4746);1.5977(1.0395).

[0387] conclusion The chemical shift values ​​and peak integrals correspond to the expected salts.

[0388] Example 6: Solubility of AP1189 and its salts method The solubility of the acetate (XRPD pattern 1), fumarate (XRPD pattern 1) and succinate (XRDP pattern 1) salts of AP1189 was evaluated in 0.5 M buffer solutions having a pH of 1.2 and 4.5.

[0389] result The results of this study are shown in Tables 38a and 38b for 0.5M and 0.2M buffer, respectively. Table 38c shows the solubility of additional salts of AP1189.

[0390] For 0.5M buffer, the highest solubility was observed for acetate Pattern 1. Higher solubility was observed for succinate Pattern 1 compared to fumarate Pattern 1. XRPD analysis showed that acetate Pattern 1 remained at pH 4.5. At pH 1.2 for acetate, a likely HCl salt (assigned as HCl Pattern 1) was formed. Succinic acid was obtained at pH 1.2 from the succinate Pattern 1 experiment. Free succinic acid in the residual solids may indicate that the system was not saturated with respect to the API and that the solubility may be higher than reported. [Table 38] JPEG2024523459000052.jpg151159

[0391] conclusion The test compounds exhibited significantly different solubilities, especially at low pH: specifically, the acetate and succinate salts exhibited high solubility at pH 1.2, indicating the potential use of these compounds in applications where high solubility at low pH is desirable.

[0392] Example 7: Polymorphic Study of AP1189 Succinate Materials and Methods Approximately 300 mg of the received succinate salt was added to a 14 mL vial. The required volume of the appropriate solvent system was added to each vial and the runs were stirred at 70-73 °C until completely dissolved. These runs were then cooled to 68 °C and seeded with AP1189 succinate salt. A seed loading of 5-15% was used. These runs were stirred at 68 °C for an additional hour to allow equilibration. The runs were then cooled to 5 °C at 0.1 °C / min and stirred at 5 °C until isolated. The runs (slurries) were vacuum filtered and the cakes were washed with 3 mL of each respective input solvent system (pre-cooled at 5 °C). The solids were analyzed by XRPD to confirm the polymorphic form. The solid residue was dried under vacuum at ambient temperature for approximately 3 days. Characterization of the dried solids was performed. The concentrations of the collected mother liquors were measured by HPLC.

[0393] result Both the wet and dry crystallized solids were consistent with the succinate salt Pattern 1. Table 39 summarizes the findings of this study. [Table 39]

[0394] conclusion Using various crystallization conditions, AP1189 succinate exhibiting pattern 1 crystal morphology was obtained.

[0395] Example 8: Polymorphic study of AP1189 succinate salt Materials and Methods Approximately 300 mg of AP1189 was added to a 20 mL vial. The required volume of the appropriate solvent system was added to each vial and the runs were stirred at 65-69°C. The runs were then cooled to 55°C and seeded with AP1189 succinate. A seed loading of 2% was used. The runs were stirred at 55°C for an additional hour to allow equilibration. The runs were then cooled to 5°C at 0.1°C / min and stirred at 5°C. After stirring at about 5°C for about 18 hours, a 200 μL aliquot of each slurry was extracted and centrifuged using 0.2 μm nylon tubes. The isolated solids were dried under vacuum at ambient temperature and analyzed by HPLC (purity). The concentration and purity of the mother liquor were also measured by HPLC. Anti-solvent addition to the remainder of the runs was performed at 5°C to reach the target final ratio. Stirring was then continued at about 5°C for about 4 more hours. The runs (slurries) were vacuum filtered and the cakes were washed with 0.9 mL of each organic solvent (pre-chilled at 5° C.). The solids were dried under vacuum at room temperature for approximately 48 hours. The dried solids were characterized. An aliquot of the mother liquor was sampled and analyzed by HPLC for determination of concentration and solution purity. The remaining mother liquor was left open in the oven and the solvent was evaporated under vacuum at room temperature. After 3 days the remaining solids were analyzed by XRPD and HPLC (purity).

[0396] result All isolated solids were consistent with succinate Pattern 1. Table 40 summarizes the findings of this study. [Table 40]

[0397] conclusion Using various crystallization conditions, AP1189 succinate salt was obtained that exhibited crystal morphology of pattern 1. The isolated yields obtained were between 65-80%. The addition of water as an antisolvent improved the theoretical yield by 2-6% wt.%.

[0398] Example 9: Polymorphic Study of AP1189 Succinate Materials and Methods Approximately 5 g of AP1189 succinate was added to a temperature controlled reactor in an EasyMax 102 (100 mL vessel). 55.6 mL (11.1 volumes) of 1-propanol / water (50:50 v / v%) was added to the reactor and the experiment was stirred at 70° C. The target concentration was 90 mg / mL. The stirring speed was 200 rpm. Once complete dissolution was observed, the experiment was cooled to 55° C. and seeded with AP1189 succinate. A seed load of 2% was used and was sustained with evidence of slurry formation. After seeding, stirring was continued at 55° C. for 2 hours to allow the experiment to equilibrate. The experiment was cooled to 5° C. at 0.1° C. / min and stirred at 5° C. for 1 hour. The stirring speed was increased to 300 rpm during the cooling process. At 5°C, water (pH 7.22) was added as anti-solvent at 1 vol / hr to reach a target ratio of 40:60% v / v. 14 mL (2.8 vol) water was added. Stirring was continued at 5°C for approximately 6 hours after addition. A portion of the slurry was extracted into a 0.2 μm nylon tube and centrifuged. The concentration and solution purity of the isolated mother liquor were determined by HPLC. The isolated solid was dried under vacuum at ambient temperature for approximately 4 days and analyzed by HPLC for purity analysis. At 5°C, more water was added as anti-solvent at 1 vol / hr to reach a target ratio of 30:70% v / v. 23.4 mL (4.6 vol) water was added. The stirring speed was further increased to 350 rpm during the addition. Stirring was continued at 5°C for an additional 90 minutes after addition. At 5°C, the slurry was vacuum filtered using a Buchner funnel. The filter cake was washed with 10 mL (2 volumes) of water (pre-cooled to 5° C.) and dried under vacuum at ambient temperature for approximately 4 days. XRPD analysis was performed on both the wet and dried solid samples. The dried solids were characterized. An aliquot of 10 mL of the mother liquor was left open in the oven to evaporate the solvent under vacuum at ambient temperature. The residual solids were analyzed by XRPD and HPLC (purity). The concentration and solution purity of the remaining mother liquor and washes were determined by HPLC.

[0399] result All samples were consistent with AP1189 succinate salt with XRPD pattern 1. The results are shown in Table 41. [Table 41]

[0400] conclusion AP1189 succinate exhibiting pattern 1 crystal morphology was obtained.

[0401] Example 10: Polymorphic study of AP1189 succinate salt Materials and Methods Approximately 10 g of AP1189 succinate was added to a temperature controlled reactor in an EasyMax 402 (400 mL vessel). 100 mL (10 volumes) of 1-propanol:water (50:50 v / v%) was added to the reactor and the experiment was stirred at 68°C. The concentration was 100 mg / mL. The stirring speed was 200 rpm. Once complete dissolution was observed, the experiment was polish filtered at 70°C to remove insoluble impurities and the filtrate was returned to the reactor. 5 mL (0.5 volumes) of 1-propanol:water (50:50 v / v%) was used to wash the reactor and passed through the filter. 7 mL (0.7 volumes) of 1.propanol:water (50:50 v / v%) was used to filter into the reactor. The concentration was 90 mg / mL. The experiment was equilibrated at 65°C and then cooled to 55°C. The experiment was seeded at 55° C. with AP1189 succinate salt at 1% seed loading. After seeding, the experiment was allowed to equilibrate at 55° C. for approximately 1 hour. At 5° C., water was added as antisolvent at 1 vol / hr to reach a target ratio of 30:70% v / v. 74.7 mL (7.4 vol) water was added. During the addition, the stirring speed was increased stepwise to 250 rpm. After the addition, stirring was continued at 5° C. for approximately 2.5 hours. At 5° C., the slurry was vacuum filtered using a Buchner funnel. The filter cake was washed with 10 mL (1 vol) water (pre-cooled to 5° C.) and dried under vacuum at ambient temperature for approximately 4 days. XRPD analysis was performed on both the wet and dried solid samples. The dried solid was characterized. An aliquot of 10 mL of the mother liquor was left open in the oven to evaporate the solvent under vacuum at ambient temperature. The residual solids were analyzed by XRPD and HPLC (purity). The concentrations and solution purities of the remaining mother liquors and washes were determined by HPLC.

[0402] result All samples were consistent with AP1189 succinate salt with XRPD pattern 1. The results are shown in Table 42. [Table 42]

[0403] conclusion AP1189 succinate exhibiting pattern 1 crystal morphology was obtained.

[0404] Example 11: Further solubility studies of AP1189 acetate and AP1189 succinate Materials and Methods To separate vials containing 10.0 mL of buffer pH 1.2, 3.4 g of AP1189 succinate and 2.9 g of AP1189 acetate were added (one measurement per salt). The pH of the AP1189 acetate and AP1189 succinate solutions was measured to be 3.9 and 2.2, respectively. As a result, the pH was adjusted to 1.2 in both solutions with concentrated hydrochloric acid. Both sample preparations were diluted 500-fold with sample diluent (acetonitrile:water 1:1 v / v).

[0405] The diluted sample preparations were analyzed by HPLC within 5 hours of preparation, and the content of AP1189 was determined from the area under the curve by comparison with standard solutions of AP1189 acetate and AP1189 succinate, respectively.

[0406] Equilibrium solubility was also evaluated at pH 4.5 and pH 6.8 according to the procedure described in WHO Technical Report Series 1019, 2019 annex 4: Protocol to conduct equilibrium solubility experiments for the purpose of Biopharmaceutics Classification System-based classification of active pharmaceutical ingredients for bioward.

[0407] result The sample material in both vials was allowed to dissolve completely before dilution.

[0408] The solubility of the test compounds at pH 1.2 is shown in Table 43. The solubility of the test compounds at pH 4.5 and pH 6.8 is shown in Table 44, where all were found to have purities within 92%-95%. [Table 43] [Table 44]

[0409] Example 12: Preparation of further polymorphs of AP1189 salts Tosylate Pattern 1 The tosylate salt of AP1189, having XRPD pattern 1, was prepared by crystallization from methanol.

[0410] Fumarate Pattern 1 The fumarate salt of AP1189, having XRPD pattern 1, was prepared by crystallization from isopropyl alcohol:water 90:10 v / v.

[0411] Naphthalene-1,5-disulfonic acid pattern 1 Naphthalene-1,5-disulfonic acid with XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of 2-propanol:water 90:10% v / v. An additional 500 μL of 2-propanol:water 90:10% v / v was added to the naphthalene-1,5-disulfonic acid (1.1 molar equivalents), which was then pipetted into the API. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 hour isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD.

[0412] Naphthalene-1,5-disulfonic acid pattern 2 Naphthalene-1,5-disulfonic acid with XRPD pattern 2 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of THF. An additional 500 μL of THF was added to the naphthalene-1,5-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 hour isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0413] Ethanesulfonic acid pattern 1 Ethanesulfonic acid, having XRPD pattern 1, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of methyl ethyl ketone. Ethanesulfonic acid (1.1 molar equivalents) was transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solids were isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD.

[0414] Ethane-1,2-disulfonic acid pattern 1 Ethane-1,2-disulfonic acid, having XRPD pattern 1, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of 2-propanol:water (80:20% v / v). An additional 500 μL of 2-propanol:water (80:20% v / v) was added to ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD to give pattern 1. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD to give pattern 5. After storage at 40° C. / 75% RH for 24 hours, the diffractogram was consistent with pattern 1 by XRPD.

[0415] Ethane-1,2-disulfonic acid pattern 2 Ethane-1,2-disulfonic acid, having XRPD pattern 2, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of methyl ethyl ketone. An additional 500 μL of methyl ethyl ketone was added to ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0416] Ethane-1,2-disulfonic acid pattern 4 Ethane-1,2-disulfonic acid, having XRPD pattern 4, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of THF. An additional 500 μL of THF was added to ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0417] Ethane-1,2-disulfonic acid pattern 5 Ethane-1,2-disulfonic acid having XRPD pattern 5 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of 2-propanol:water (80:20% v / v). An additional 500 μL of 2-propanol:water (80:20% v / v) was added to ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 hour isothermal hold at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0418] Nitric acid pattern 1 Nitric acid having XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of THF. Nitric acid (1.1 molar equivalents) was transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 hour isothermal hold at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0419] Cyclamic acid pattern 2 Cyclamic acid having XRPD pattern 2 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of THF. An additional 500 μL of THF was added to cyclamic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0420] Cyclamic acid pattern 4 Cyclamic acid having XRPD pattern 4 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of acetone. An additional 500 μL of acetone was added to cyclamic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0421] Cyclamic Acid Pattern 5 Cyclamic acid having XRPD pattern 5 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of THF. An additional 500 μL of THF was added to ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD. After storage at 40° C. / 75% RH for 24 h, the diffractogram was consistent with pattern 5 by XRPD.

[0422] Benzenesulfonic acid pattern 1 Benzenesulfonic acid having XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of 2-propanol:water 80:20% v / v. Benzenesulfonic acid (1.1 molar equivalents) was transferred to the API via pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solids were isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD.

[0423] Oxalic Acid Pattern 1 Oxalic acid having XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of 2-propanol:water 80:20% v / v. An additional 500 μL of 2-propanol:water 80:20% v / v was added to the oxalic acid (1.1 molar equivalents), which was then pipetted into the API. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 hour isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0424] Oxalic Acid Pattern 2 Oxalic acid having XRPD pattern 2 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of acetone. An additional 500 μL of acetone was added to the oxalic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0425] Oxalic Acid Pattern 4 Oxalic acid having XRPD pattern 4 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of THF. An additional 500 μL of THF was added to oxalic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0426] (+)-Camphor-10-sulfonic acid pattern 1 (+)-Camphor-10-sulfonic acid with XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of 2-propanol:water 80:20% v / v. (+)-Camphor-10-sulfonic acid (1.1 molar equivalents) was transferred to the API via pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0427] Ketoglutarate Pattern 1 Ketoglutaric acid having XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of acetone. Ketoglutaric acid (1.1 molar equivalents) was transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solids were isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD.

[0428] DL-Mandelic acid pattern 2 DL-Mandelic acid, having XRPD pattern 2, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of methyl ethyl ketone. An additional 500 μL of methyl ethyl ketone was added to DL-mandelic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0429] DL-Mandelic acid pattern 3 DL-Mandelic acid, having XRPD pattern 3, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of acetone. An additional 500 μL of acetone was added to DL-mandelic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0430] Hippuric acid pattern 1 Hippuric acid, having XRPD pattern 1, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of methyl ethyl ketone. An additional 500 μL of methyl ethyl ketone was added to hippuric acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0431] Formic acid pattern 1 Formic acid, having XRPD pattern 1, was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of acetone. Formic acid (1.1 molar equivalents) was transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1 h isothermal hold at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 h and then reanalyzed by XRPD.

[0432] L-Lactic Acid Pattern 1 L-Lactic acid having XRPD pattern 1 was prepared as follows: 50 mg of AP1189 acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 μL of acetone. An additional 500 μL of acetone was added to L-lactic acid (1.1 molar equivalents), which was then transferred to the API by pipette. The resulting mixture was thermocycled between 40° C. and 5° C. for 3 days (ramp rate: 0.1° C. / min with 1-h isothermal holds at 40° C. and 5° C.). The solid was isolated by centrifugal filtration and wet analyzed by XRPD. The sample was dried under vacuum at 40° C. for 24 hours and then reanalyzed by XRPD.

[0433] ...

Claims

**Claim 1** A crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium salt, i. Crystal form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate, which exhibits at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu K α radiation at 11.5 ± 0.2, 23.5 ± 0.2 and 27.0 ± 0.2, said crystal form A ii. Crystalline Form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate, said Crystalline Form B showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 9.7±0.2, 22.8±0.2 and 26.7±0.2, iii. Crystalline Form XIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium besylate, said Crystalline Form XIV showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 13.0±0.2, 15.1±0.2 and 19.9±0.2, iv. Crystalline Form XIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxoglutarate, said Crystalline Form XIX showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 16.8±0.2, 23.4±0.2 and 23.6±0.2, v. Crystalline Form XX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-mandelate, said Crystalline Form XX showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 14.8±0.2, 24.2±0.2 and 25.5±0.2, vi. Crystalline Form XXII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium hippurate, said Crystalline Form XXII showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 20.1±0.2, 24.1±0.2 and 24.5±0.2, vii. Crystal form XXIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium formate, said crystal form XXIII showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 13.3 ± 0.2, 15.1 ± 0.2 and 25.6 ± 0.2, viii. Crystal form XXIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium L-lactate, said crystal form XXIV showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 3.8 ± 0.2, 9.9 ± 0.2 and 11.9 ± 0.2, ix. Crystal form XXV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-lactate, said crystal form XXV showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 9.8 ± 0.2, 11.9 ± 0.2 and 27.6 ± 0.2, x. Crystal form XXVI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium glutarate, said crystal form XXVI showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 8.3 ± 0.2, 15.9 ± 0.2 and 21.9 ± 0.2, and xi. Crystal form XXIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium adipate, said crystal form XXIX showing at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 13.4 ± 0.2, 14.5 ± 0.2 and 25.5 ± 0.2 The crystal form selected from the group consisting of Claim 2 Cu K selected from the group consisting of 11.7 ± 0.2, 13.0 ± 0.2, 15.5 ± 0.2, 15.6 ± 0.2, 16.2 ± 0.2, 19.6 ± 0.2, 20.0 ± 0.2, 21.1 ± 0.2 and 24.8 ± 0.2 α further showing, in the powder diffraction pattern, one or more X-ray lines (2θ values) when measured using α radiation, and / or The crystalline form A does not include the second crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate, and when the second form is measured using Cu Kα radiation at 14.9 ± 0.2, 18.0 ± 0.2, and / or 24.2 ± 0.2, it shows an X-ray line (2θ value) in the powder diffraction pattern. The crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate according to claim 1, or When measured using Cu Kα radiation selected from the group consisting of 5.4 ± 0.2, 12.2 ± 0.2, 13.4 ± 0.2, 15.8 ± 0.2, 16.3 ± 0.2, 19.5 ± 0.2, 21.8 ± 0.2, and 28.5 ± 0.2, it further shows one or more X-ray lines (2θ values) in the powder diffraction pattern. The crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate according to claim 1. **Claim 3** The crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate according to claim 1, which shows an onset temperature between 185 and 199 °C when using a heating rate of 10 °C per minute in differential scanning calorimetry, or an onset temperature of 192 °C when using a heating rate of 10 °C per minute, or The crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate according to claim 1, which shows an onset temperature between 187 and 201 °C when using a heating rate of 10 °C per minute in differential scanning calorimetry, or an onset temperature of 195 °C when using a heating rate of 10 °C per minute. **Claim 4** A method for producing the crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate according to claim 1, or the crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate according to claim 1, comprising: i. Mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine and acetic acid in a solvent to form a mixture; ii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in crystalline form A from the mixture, or i. mixing a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine and acetic acid in a solvent to form a mixture; ii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in crystalline form A from the mixture, or i. mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in a solvent to form a composition; ii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in crystalline form A from the mixture, or i. mixing 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-propanal, aminoguanidine or a salt thereof, and acetic acid or a salt thereof in a solvent; ii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in crystalline form A from the composition, or i. providing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine or a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium; ii. introducing acetate as a counterion using ion exchange; iii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate in crystalline form A, or i. mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine and succinic acid in a solvent to form a mixture; ii. isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate in crystalline form B from the mixture, or i. Mixing a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium with succinic acid in a solvent to form a mixture; ii. Isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate in crystalline form B from the said mixture, or i. Mixing 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal, aminoguanidine or its salt, and succinic acid or its salt in a solvent; ii. Isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate in crystalline form B from the said composition, or i. Providing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine or a salt of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium; ii. Introducing a succinate as a counter ion using ion exchange; iii. Isolating the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate in crystalline form B, the said method.

5. A pharmaceutical composition for use in medicine, wherein the composition comprises crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate according to claim 1, crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate according to claim 1, crystalline form XIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium besylate according to claim 1, crystalline form XIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxoglutarate according to claim 1, crystalline form XX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-mandelate according to claim 1, The crystalline form XXII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium hippurate according to claim 1, The crystalline form XXIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium formate according to claim 1, The crystalline form XXIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium L-lactate according to claim 1, The crystalline form XXV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-lactate according to claim 1, The crystalline form XXVI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium glutarate according to claim 1, or The pharmaceutical composition comprising the crystalline form XXIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium adipate according to claim 1.

6. A pharmaceutical composition for use in the treatment of renal diseases, arthritis diseases, cardiovascular diseases, atherosclerosis, viral diseases or disorders, or systemic inflammatory diseases, systemic inflammatory diseases which are autoimmune diseases, or Behçet's disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, Sjögren's syndrome, myositis including dermatomyositis and polymyositis, vasculitis, giant cell arteritis, ankylosing spondylitis, rheumatoid polymyalgia or psoriatic arthritis, wherein the composition comprises The crystalline form A of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate according to claim 1, The crystalline form B of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium succinate according to claim 1, The crystalline form XIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium besylate according to claim 1, The crystalline form XIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxoglutarate according to claim 1, The crystalline form XX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-mandelate according to claim 1, The crystalline form XXII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium hippurate according to claim 1, The crystalline form XXIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium formate according to claim 1, The crystalline form XXIV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium L-lactate according to claim 1, The crystalline form XXV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-lactate according to claim 1, The crystalline form XXVI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium glutarate according to claim 1, or The pharmaceutical composition comprising the crystalline form XXIX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium adipate according to claim 1.

7. The kidney disease is i. Kidney diseases presenting proteinuria, ii. Kidney diseases due to proteinuria, iii. Glomerular diseases, iv. Nephrotic syndrome (glomerulonephritis), v. Membranous glomerulonephritis (MGN) (or membranous nephropathy (MN)), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN) (membranocapillary glomerulonephritis), type 1 MPGN, type 2 MPGN, rapidly progressive glomerulonephritis (RPGN) (crescentic GN), minimal change disease (MCD), or IgA nephropathy (Berger's disease), IgM nephropathy, post-infectious glomerulonephritis and thin basement membrane disease, and includes primary nephrotic syndrome (primary glomerulonephritis) selected from the group consisting of glomerulonephritis, vi. Secondary nephrotic syndrome (secondary glomerulonephritis), including secondary nephrotic syndrome caused by underlying autoimmune diseases, underlying cancer diseases, underlying genetic diseases, selected from the group consisting of systemic lupus erythematosus (SLE), diabetic nephropathy, sarcoidosis, Sjogren's syndrome, amyloidosis, multiple myeloma, vasculitis, cancer, and genetic diseases including congenital nephrotic syndrome, urinary tract infections, HIV, syphilis, hepatitis including hepatitis A, hepatitis B, and hepatitis C, post-streptococcal infection, schistosomiasis mansoni of the bladder, and infections including Ebola. vii. Inflammatory kidney diseases viii. Glomerulonephritis (GN), and ix. The pharmaceutical composition for use according to claim 6, selected from the group consisting of idiopathic membranous nephropathy (iMN).

8. wherein the arthritis disease is i. Autoimmune diseases, inflammatory diseases presenting joint inflammation, systemic lupus erythematosus, mixed connective tissue disease, Still's disease, and polymyalgia rheumatica ii. Inflammatory arthritis, including rheumatoid arthritis (RA), severe active RA (CDAI > 22), severe active RA with a DAS28 score greater than 5.1, juvenile rheumatoid arthritis (JRA), psoriatic arthritis, and ankylosing spondylitis, selected from the group consisting of iii. Degenerative arthritis or osteoarthritis iv. Metabolic arthritis or gouty arthritis v. Reactive arthritis, or arthritis associated with infection by one or more of hepatitis C, Chlamydia, Neisseria gonorrhoeae, Salmonella, or Shigella vi. Infectious arthritis, or arthritis associated with infection by one or more of hepatitis C, Chlamydia, Neisseria gonorrhoeae, Salmonella, or Shigella, and vii. The pharmaceutical composition for use according to claim 6, selected from the group consisting of arthritis as part of a systemic inflammatory disease.

9. wherein the viral disease or disorder is i. Symptomatic viral disease or disorder ii. Symptomatic viral disease or disorder with inflammation iii. Inflammatory viral disease or disorder iv. Viral respiratory infections, including viral lower respiratory tract infections v. Viral respiratory diseases or disorders vi. Viral diseases or disorders of the lung vii. Viral diseases or disorders with inflammation in the lung, or viral diseases or disorders with inflammation in the respiratory system, including viral diseases or disorders with inflammation in the lung or in the respiratory system. viii. A viral disease or disorder with one or more respiratory symptoms, including one or more respiratory symptoms selected from the group consisting of cough, dry cough, dyspnea, oxygen supply disorder, respiratory disease, respiratory insufficiency, respiratory failure, respiratory syndrome, and acute respiratory disease (ARD). ix. A severe disease, including a severe disease presenting with dyspnea, increased respiratory rate, decreased blood oxygen saturation, or pulmonary infiltration. x. A serious disease, including a serious disease presenting with respiratory failure, septic shock, multiple organ dysfunction (MOD) or multiple organ failure (MOF). xi. Viral pneumonia xii. Viral bronchiolitis xiii. A viral disease or disorder with respiratory failure xiv. Acute respiratory distress syndrome (ARDS) xv. Viral acute respiratory distress syndrome (ARDS) xvi. Symptomatic COVID-19 with acute respiratory distress syndrome (ARDS) xvii. A viral disease or disorder with systemic inflammatory response syndrome (SIRS) and / or sepsis xviii. A viral disease or disorder with lung dysfunction xix. A viral disease or disorder with cytokine release syndrome (CRS) and / or cytokine storm (hypercytokinemia), and xx. Selected from the group consisting of viral diseases or disorders caused by viral infections selected from the group consisting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); SARS-CoV, MERS-CoV, dengue virus, and influenza virus (including types A, B, and C). The pharmaceutical composition for use according to claim 6, wherein the inflammation includes hyperinflammation, including hyperinflammation in one or more organs including the lungs, respiratory system, kidneys, liver, pancreas, spleen, exocrine glands, endocrine glands, lymph nodes, brain, heart, muscles, bone marrow, skin, skeleton, bladder, genital organs including fallopian tubes, eyes, ears, vascular system, small intestine, colon, rectum, digestive tract including anal canal, and prostate.

10. The cardiovascular disease is i. Coronary artery disease (CAD), including angina pectoris and myocardial infarction. ii. Stroke iii. Heart failure iv. Hypertensive heart disease v. Rheumatic heart disease vi. Cardiomyopathy vii. Abnormal heart rhythm viii. Congenital heart disease ix. Valvular heart disease x. Carditis xi. Aortic aneurysm xii. Peripheral artery disease xiii. Vascular disease xiv. Thromboembolic disease xv. Venous thrombosis xvi. Vascular inflammation, and

11. The pharmaceutical composition for use according to claim 6, wherein the treatment is the treatment of rheumatoid arthritis in a subject showing an inappropriate response to MTX, and the inappropriate response to MTX is a reduced response to MTX treatment or a non-responder to MTX.

12. A method for producing a crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt according to claim 1, comprising: i. mixing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine and an acid in a solvent to form a mixture; ii. isolating the crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt from the mixture, or i. mixing a second N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt and an acid in a solvent to form a mixture; ii. isolating the crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt from the mixture, or i. mixing an amorphous form or a second crystalline form of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt in a solvent to form a composition; ii. isolating the crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt from the composition, or i. mixing 3-[1-(2-nitrophenyl)-1-H-pyrrol-2-yl]-propanal, aminoguanidine or a salt thereof, and an acid or a salt thereof in a solvent; ii. isolating the crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salt from the composition, or ​ i. Providing N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidine or a second N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium salt; ii. Introducing a counter ion of an acid ion using ion exchange; iii. Isolating the crystalline form of the N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium salt, said method comprising the above. **Claim 13** A crystalline form of an N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium salt, wherein: i. Crystalline Form C of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium tosylate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 14.5 ± 0.2, 21.0 ± 0.2 and 25.2 ± 0.2, said Crystalline Form C; ii. Crystalline Form D of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium fumarate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 17.6 ± 0.2, 21.2 ± 0.2 and 26.3 ± 0.2, said Crystalline Form D; iii. Crystalline Form I of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate, which shows X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at one or more of 11.5 ± 0.2, 11.7 ± 0.2, 12.9 ± 0.2, 14.9 ± 0.2, 15.4 ± 0.2, 15.6 ± 0.2, 18.0 ± 0.2, 19.9 ± 0.2, 20.0 ± 0.2, 21.1 ± 0.2, 21.5 ± 0.2, 21.8 ± 0.2, 22.4 ± 0.2, 23.5 ± 0.2, 24.2 ± 0.2, 24.7 ± 0.2, and 26.9 ± 0.2, said Crystalline Form I; iv. Crystal form II of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium acetate, which shows X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at one or more of 7.5 ± 0.2, 9.4 ± 0.2, 12.8 ± 0.2, 13.3 ± 0.2, 14.2 ± 0.2, 15.3 ± 0.2, 16.0 ± 0.2, 17.0 ± 0.2, 18.8 ± 0.2, 19.7 ± 0.2, 20.3 ± 0.2, 21.1 ± 0.2, 21.4 ± 0.2, 21.9 ± 0.2, 22.0 ± 0.2, 22.7 ± 0.2, and 23.1 ± 0.2, said crystal form II v. Crystal form III of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium napadisylate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 13.4 ± 0.2, 22.2 ± 0.2 and 26.8 ± 0.2, said crystal form III vi. Crystal form IV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium napadisylate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 5.4 ± 0.2, 15.6 ± 0.2 and 23.4 ± 0.2, said crystal form IV vii. Crystal form V of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium esylate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 14.5 ± 0.2, 16.5 ± 0.2 and 18.6 ± 0.2, said crystal form V viii. Crystal form VI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium edisylate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 4.8 ± 0.2, 12.8 ± 0.2 and 16.5 ± 0.2, said crystal form VI ix. Crystal form VII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium edisylate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 6.1 ± 0.2, 15.7 ± 0.2, and 23.6 ± 0.2, said crystal form VII, x. Crystal form VIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium edisylate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 15.5 ± 0.2, 20.7 ± 0.2, and 21.7 ± 0.2, crystal form VIII, xi. Crystal form IX of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium edisylate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 4.5 ± 0.2, 16.7 ± 0.2, and 24.7 ± 0.2, said crystal form IX, xii. Crystal form X of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium nitrate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 15.3 ± 0.2, 21.4 ± 0.2, and 25.1 ± 0.2, said crystal form X, xiii. Crystal form XI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium cyclamate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 7.0 ± 0.2, 13.8 ± 0.2, and 15.7 ± 0.2, said crystal form XI, xiv. Crystal form XII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium cyclamate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 7.3 ± 0.2, 15.3 ± 0.2, and 17.9 ± 0.2, said crystal form XII, xv. Crystal form XIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium cyclamate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 15.3 ± 0.2, 18.5 ± 0.2 and 18.7 ± 0.2, said crystal form XIII, xvi. Crystal form XV of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxalate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 19.5 ± 0.2, 23.3 ± 0.2 and 25.8 ± 0.2, said crystal form XV, xvii. Crystal form XVI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxalate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 17.1 ± 0.2, 17.9 ± 0.2 and 19.6 ± 0.2, said crystal form XVI, xviii. Crystal form XVII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium oxalate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 6.3 ± 0.2, 10.6 ± 0.2 and 19.8 ± 0.2, said crystal form XVII, xix. Crystal form XVIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium (+)-camphor-10-sulfonate, which shows at least X-ray lines (2-theta values) in the powder diffraction pattern when measured using Cu Kα radiation at 6.5 ± 0.2, 11.5 ± 0.2 and 14.8 ± 0.2, said crystal form XVIII, XX. A crystalline form XXI of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium DL-mandelate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 5.4 ± 0.2, 10.0 ± 0.2 and 24.6 ± 0.2, said crystalline form XXI, xxi. A crystalline form XXVII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium glutarate, which further shows one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation selected from the group consisting of 16.9 ± 0.2, 25.6 ± 0.2, 27.1 ± 0.2, 28.2 ± 0.2 and 28.7 ± 0.2, said crystalline form XXVII, and xxii. A crystalline form XXVIII of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-arylidene}-aminoguanidinium glutarate, which shows at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 14.2 ± 0.2, 16.9 ± 0.2 and 24.5 ± 0.2, said crystalline form XXVIII The crystalline form selected from the group consisting of.