US20230271922A9 - Polymorphs of phenyl pyrrole aminoguandium salts - Google Patents

Polymorphs of phenyl pyrrole aminoguandium salts Download PDF

Info

Publication number
US20230271922A9
US20230271922A9 US17/821,500 US202217821500A US2023271922A9 US 20230271922 A9 US20230271922 A9 US 20230271922A9 US 202217821500 A US202217821500 A US 202217821500A US 2023271922 A9 US2023271922 A9 US 2023271922A9
Authority
US
United States
Prior art keywords
crystalline form
exhibiting
nitrophenyl
pyrrol
allylidene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
US17/821,500
Other languages
English (en)
Other versions
US20230002319A1 (en
Inventor
Thomas Boesen
Thomas Engelbrecht Nordkild Jonassen
Hayley Ann Reece
Natalie Louise KELK
Alice Jane TURNER
Ross MCLELLAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synact Pharma ApS
Original Assignee
Synact Pharma ApS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synact Pharma ApS filed Critical Synact Pharma ApS
Assigned to SYNACT PHARMA APS reassignment SYNACT PHARMA APS ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BOESEN, THOMAS, JONASSEN, THOMAS ENGELBRECHT NORDKILD, TURNER, Alice Jane, KELK, Natalie Louise, MCLELLAN, Ross, REECE, Hayley Ann
Publication of US20230002319A1 publication Critical patent/US20230002319A1/en
Publication of US20230271922A9 publication Critical patent/US20230271922A9/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/402—1-aryl substituted, e.g. piretanide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/83—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/29—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/02—Formic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/02—Formic acid
    • C07C53/06—Salts thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/08—Acetic acid
    • C07C53/10—Salts thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/10—Succinic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/12—Glutaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/14—Adipic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
    • C07C59/08—Lactic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/347—Saturated compounds containing more than one carboxyl group containing keto groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
    • C07C59/48—Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings
    • C07C59/50—Mandelic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the present invention relates to salts of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine having a high solubility at low pH.
  • the melanocortin system is a set of neuropeptidergic and immuneendocrine signalling pathways that play an integral role in the homeostatic control of a diverse array of physiological functions, including melanogenesis, stress response, inflammation, immunomodulation and adrenocortical steroidogenesis. It consists of multiple components, including the five G protein-couple melanocortin receptors: melanocortin receptor 1 (MC1R) to MC5R; peptide ligands; ⁇ , ⁇ , ⁇ -melanocyte stimulating hormone ( ⁇ , ⁇ , ⁇ -MSH); adrenocorticotropic hormone (ACTH) secreted by the anterior pituitary; and endogenous antagonists.
  • MCRs melanocortin receptors
  • Phenyl pyrrole aminoguanidine derivatives with activity on the melanocortin receptors have previously been disclosed.
  • One example of such compound is the anti-inflammatory AP1189 (N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine) which was first shown to bind the MC1R and later was identified as a biased dual agonist at receptors MC1R and MC3R that does not provoke canonical cAMP generation (and hence no MC1R-induced melanogenesis) but instead appear to induce alternative pathways including ERK1/2-phosphorylation and Ca 2+ mobilisation.
  • AP1189 N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine
  • the present inventors have discovered salts of AP1189 with particularly favourable solubility profiles for gastric delivery.
  • the inventors found that certain polymorphs of AP1189 salts have very high solubilities, especially at low pH.
  • one aspect of the present disclosure provides for a crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 11.5 ⁇ 0.2, 23.5 ⁇ 0.2, and 27.0 ⁇ 0.2.
  • Another aspect of the present disclosure provides for a crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 9.7 ⁇ 0.2, 22.8 ⁇ 0.2, and 26.7 ⁇ 0.2.
  • the present disclosure also provides methods of producing such crystalline forms.
  • One aspect of the present disclosure provides a method for producing the N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate of crystalline Form A as disclosed herein, said method comprising:
  • One aspect of the present disclosure provides a method for producing the N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate of crystalline Form A as disclosed herein, said method comprising:
  • One aspect of the present disclosure provides a method for producing the N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate of crystalline Form A as disclosed herein, said method comprising:
  • One aspect of the present disclosure provides a method for producing N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate of crystalline Form B as disclosed herein, said method comprising:
  • One aspect of the present disclosure provides a method for producing N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate of crystalline Form B as disclosed herein, said method comprising:
  • One aspect of the present disclosure provides a crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate produced by a method as disclosed herein.
  • One aspect of the present disclosure provides a crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate produced by a method as disclosed herein.
  • One aspect of the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising the crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate as disclosed herein and a pharmaceutically acceptable excipient.
  • One aspect of the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising the crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate as disclosed herein and a pharmaceutically acceptable excipient.
  • One aspect of the present disclosure provides a method of preparing a pharmaceutical composition comprising mixing the crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate as disclosed herein and a pharmaceutically acceptable excipient.
  • One aspect of the present disclosure provides a method of preparing a pharmaceutical composition, said method comprising mixing the crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate as disclosed herein with a pharmaceutically acceptable excipient.
  • One aspect of the present disclosure provides a method of treating a disease or disorder in a subject in need thereof, said method comprising administering crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate as disclosed herein, the crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate as disclosed herein, or the pharmaceutical composition as disclosed herein to a subject in need thereof.
  • One aspect of the disclosure provides for a use of the crystalline Form A of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate as disclosed herein or the crystalline Form B of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate as disclosed herein, or the pharmaceutical composition as disclosed herein, for the manufacture of a medicament for treatment of a disease or disorder.
  • One aspect of the present disclosure is to provide for crystalline forms of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salts having high solubility at low pH, e.g. at pH 1.2.
  • one aspect provides for a crystalline Form of an N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt selected from the group consisting of:
  • One aspect of the present disclosure is to provide crystalline forms of 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.
  • one aspect of the present disclosure provides for a crystalline Form of an N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt selected from the group consisting of:
  • One aspect of the present disclosure is to provide for 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.
  • compositions, a pharmaceutical composition, a liquid composition, a unit dosage form, or an oral formulation comprising the crystalline forms of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt disclosed herein.
  • One aspect of the disclosure provides for use of such crystalline form of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt, composition, pharmaceutical composition, liquid composition, unit dosage form, or oral formulation in medicine.
  • One aspect of the disclosure provides for use of such crystalline form of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt, composition, pharmaceutical composition, liquid composition, unit dosage form, or oral formulation in the treatment of a kidney disease, an arthritic disease, a cardiovascular disease, atherosclerosis, a viral disease or disorder, or a systemic inflammatory disorder.
  • FIG. 1 XRPD diffractogram for AP1189 acetate salt Pattern 1 crystallised from acetonitrile.
  • FIG. 2 XRPD diffractogram for AP1189 acetate salt Pattern 1 and 2 crystallised from ethyl acetate.
  • FIG. 3 XRPD diffractogram for AP1189 acetate salt Pattern 3 crystallised from THF.
  • FIG. 4 XRPD diffractogram for AP1189 tosylate salt Pattern 1 crystallised from methanol.
  • FIG. 5 XRPD diffractogram for AP1189 fumarate salt Pattern 1 crystallised from isopropylalcohol:water 90:10 v/v.
  • FIG. 6 XRPD diffractogram for AP1189 succinate salt Pattern 1 crystallised from isopropylalcohol:water 90:10 v/v.
  • FIG. 7 TGA/DSC thermogram of AP1189 acetate Pattern 1 from 1,4-dioxane. Peak temperature: 183.75° C.; onset: 164.62° C.; enthalpy (normalised): 629.95 J/g. Weight loss: 0.001 mg; weight percent loss: 0.057%.
  • FIG. 8 DSC thermogram of AP1189 acetate Pattern 1 from acetonitrile. Peak temperature 197.86° C.; onset: 192.19° C.; enthalpy (normalised): 147.26 J/g.
  • FIG. 9 TGA/DSC thermogram of AP1189 acetate Pattern 1 & 2 from 2-methyl THF. Peak temperature: 194.18° C.; onset: 171.54° C.; enthalpy (normalised): 475.77 J/g. Weight loss: 0.021 mg; weight percent loss: 0.478%.
  • FIG. 10 TGA/DSC thermogram of AP1189 acetate Pattern 3 from THF. Peak temperature: 118.76° C.; onset: 100.62° C.; enthalpy (normalised): 138.49 J/g.
  • First weight loss segment weight loss: 0.002 mg; weight percent loss: 0.067%.
  • Second weight loss segment weight loss: 0.672 mg; weight percent loss: 18.610%.
  • FIG. 11 TGA/DSC thermogram of AP1189 tosylate Pattern 1 from IPA:water 90:10 v/v after storage at 40° C. Peak temperature: 239.24° C.; onset: 233.75° C.; enthalpy (normalised): 99.785 J/g. Weight loss: 0.006 mg; weight percent loss: 0.330%.
  • FIG. 12 TGA/DSC thermogram of AP1189 fumarate Pattern 1 from 2-propanol:water 90:10. Peak temperature: 218.27° C.; onset: 214.61° C.; enthalpy (normalised): 68.467 J/g. WE0.012 mg; weight percent loss: 0.319%.
  • FIG. 13 DSC thermogram of AP1189 succinate Pattern 1 from IPA:water 90:10 v/v. Peak temperature: 196.27° C.; onset: 195.18° C.; enthalpy (normalised): 196.27 J/g.
  • FIG. 14 XRPD Diffractogram of AP1189 Napadisylate Pattern 1.
  • FIG. 15 XRPD Diffractogram of AP1189 Napadisylate Pattern 2.
  • FIG. 16 XRPD Diffractogram of AP1189 Esylate Pattern 1.
  • FIG. 17 XRPD Diffractogram of AP1189 Edisylate Pattern 1.
  • FIG. 18 XRPD Diffractogram of AP1189 Edisylate Pattern 2.
  • FIG. 19 XRPD Diffractogram of AP1189 Edisylate Pattern 4.
  • FIG. 20 XRPD Diffractogram of AP1189 Edisylate Pattern 5.
  • FIG. 21 XRPD Diffractogram of AP1189 Nitrate Pattern 1.
  • FIG. 22 XRPD Diffractogram of AP1189 Cyclamate Pattern 2.
  • FIG. 23 XRPD Diffractogram of AP1189 Cyclamate Pattern 4.
  • FIG. 24 XRPD Diffractogram of AP1189 Cyclamate Pattern 5.
  • FIG. 25 XRPD Diffractogram of AP1189 Besylate Pattern 1.
  • FIG. 26 XRPD Diffractogram of AP1189 Oxalate Pattern 1.
  • FIG. 27 XRPD Diffractogram of AP1189 Oxalate Pattern 2.
  • FIG. 28 XRPD Diffractogram of AP1189 Oxalate Pattern 4.
  • FIG. 29 XRPD Diffractogram of AP1189 (+)-Camphor-10-sulfonic acid Pattern 1.
  • FIG. 30 XRPD Diffractogram of AP1189 Oxoglutarate Pattern 1.
  • FIG. 31 XRPD Diffractogram of AP1189 DL-mandelic acid Pattern 2.
  • FIG. 32 XRPD Diffractogram of AP1189 DL-mandelic acid Pattern 3.
  • FIG. 33 XRPD Diffractogram of AP1189 Hippuric acid Pattern 1.
  • FIG. 34 XRPD Diffractogram of AP1189 Formic acid Pattern 1.
  • FIG. 35 XRPD Diffractogram of AP1189 DL-Lactic acid Pattern 1.
  • FIG. 36 XRPD Diffractogram of AP1189 DL-Lactic acid Pattern 1.
  • FIG. 37 XRPD Diffractogram of AP1189 Glutaric acid Pattern 1.
  • FIG. 38 XRPD Diffractogram of AP1189 Glutaric acid Pattern 1.
  • FIG. 39 XRPD Diffractogram of AP1189 Adipic acid Pattern 1.
  • FIG. 40 TG/DSC thermogram of AP1189 Napadisylate Pattern 1. Weight loss: 0.1356 mg. Weight Percent Loss: 3.974%. Enthalpy (normalised): 29.422 J/g; Onset x: 87.38° C.; peak temperature: 104.76° C. Enthalpy (normalised): 1.8937 J/g; Peak temperature: 187.47° C.
  • FIG. 41 TG/DSC thermogram of AP1189 Esylate Pattern 1. Weight Loss: 0.032 mg. Weight Percent Loss: 0.911%. Enthalpy (normalised): 42.119 J/g; Onset x: 201.95° C.; Peak temperature: 207.06° C.
  • FIG. 42 TG/DSC thermogram of AP1189 Edisylate Pattern 2. Weight Loss: 0.061 mg. Weight Percent Loss: 1.175%. Weight Loss: 0.158 mg. Weight Percent Loss: 3.040%. Enthalpy (normalised): 3.1886 J/g; Onset x: 220.71° C.; Peak temperature: 224.57° C.
  • FIG. 43 TG/DSC thermogram of AP1189 Edisylate Pattern 4. Weight Loss: 1.463 mg. Weight Percent Loss: 6.372%. Enthalpy (normalised): 100.17 J/g. Onset x: 208.40° C.; Peak temperature: 217.37° C.
  • FIG. 44 TG/DSC thermogram of AP1189 Edisylate Pattern 5. Weight Loss: 0.120 mg. Weight Percent Loss: 4.701%. Enthalpy (normalised): 54.800 J/g; Onset x: 58.52° C.; Peak temperature: 78.51° C. Enthalpy (normalised): 0.93567 J/g; Onset x: Not found; Peak temperature: 151.11° C.
  • FIG. 45 TG/DSC thermogram of AP1189 Nitrate Pattern 1. Weight Loss: 0.095 mg. Weight Percent Loss: 2.139%. Enthalpy (normalised): 0.4851 J/g; Onset x: 178.54° C.; Peak temperature: 182.88° C.
  • FIG. 46 TG/DSC thermogram of AP1189 Cyclamate Pattern 2. Weight Loss: 0.033 mg. Weight Percent Loss: 0.459%. Enthalpy (normalised): 6.4491 J/g; Onset x: 129.90° C.; Peak temperature: 137.27° C.
  • FIG. 47 TG/DSC thermogram of AP1189 Cyclamate Pattern 4. Weight Loss: 0.041 mg. Weight Percent Loss: 1.080%. Weight Loss: 0.088 mg. Weight Percent Loss: 2.337%. Enthalpy (normalised): 0.0143 J/g; Onset x: 133.07° C.; Peak temperature: 138.20° C.
  • FIG. 48 TG/DSC thermogram of AP1189 Besylate Pattern 1. Weight Loss: 0.014 mg. Weight Percent Loss: 2.369%. Enthalpy (normalised): 48.524 J/g; Onset x: 216.45° C.; Peak temperature: 220.49° C.
  • FIG. 49 TG/DSC thermogram of AP1189 Oxalate Pattern 1. Weight Loss: 0.023 mg. Weight Percent Loss: 1.665%. Enthalpy (normalised): 0.32686 J/g; Peak temperature: 210.52° C.
  • FIG. 50 TG/DSC thermogram of AP1189 Oxalate Pattern 2. Weight Loss. 0.035 mg. Weight Percent Loss: 2.156%. Enthalpy (normalised): 40.935 J/g; Onset x: 207.42° C.; Peak temperature: 211.50° C.
  • FIG. 51 TG/DSC thermogram of AP1189 Oxalate Pattern 4. Weight Loss: 0.016 mg. Weight Percent Loss: 2.164%.
  • FIG. 52 TG/DSC thermogram of AP1189 (+)-Camphor-10-sulfonic acid Pattern 1. Weight Loss: 0.017 mg. Weight Percent Loss: 1.843%. Enthalpy (normalised): 107.65 J/g; Onset x: 205.38° C.; Peak temperature: 209.93° C.
  • FIG. 53 TG/DSC thermogram of AP1189 Oxoglutarate Pattern 1. Weight Loss: 0.167 mg. Weight Percent Loss: 2.379%. Weight Loss: 0.462 mg. Weight Percent Loss: 6.588%. Enthalpy (normalised): 68.335 J/g. Onset x: 81.31° C. Peak temperature: 87.92° C.
  • FIG. 54 TG/DSC thermogram of AP1189 DL-mandelic acid Pattern 2. Weight Loss: 0.424 mg. Weight Percent Loss: 8.372%. Enthalpy (normalised): 43.266 J/g; Onset x: 104.13° C.; Peak temperature: 110.06° C.
  • FIG. 55 TG/DSC thermogram of AP1189 DL-mandelic acid Pattern 3. Weight Los: 0.066 mg. Weight Percent Loss: 3.021%. Weight Loss: 0.081 mg. Weight Percent Loss: 3.698%.
  • FIG. 56 TG/DSC thermogram of AP1189 Hippuric acid Pattern 1. Weight Loss: 0.022 mg. Weight Percent Loss: 1.294%. Weight Loss: 0.026 mg. Weight Percent Loss: 1.495%. Enthalpy (normalised): 4.7263 J/g; Onset x: 138.92° C.; Peak temperature: 149.72° C.
  • FIG. 57 FT-IR Spectrum of AP1189 Napadisylate Pattern 1.
  • FIG. 58 FT-IR Spectrum of AP1189 Napadisylate Pattern 2.
  • FIG. 59 FT-IR Spectrum of AP1189 Esylate Pattern 1.
  • FIG. 60 FT-IR Spectrum of AP1189 Edisylate Pattern 2.
  • FIG. 61 FT-IR Spectrum of AP1189 Edisylate Pattern 4.
  • FIG. 62 FT-IR Spectrum of AP1189 Edisylate Pattern 5.
  • FIG. 63 FT-IR Spectrum of AP1189 Nitrate Pattern 1.
  • FIG. 64 FT-IR Spectrum of AP1189 Cyclamate Pattern 2.
  • FIG. 65 FT-IR Spectrum of AP1189 Cyclamate Pattern 4.
  • FIG. 66 FT-IR Spectrum of AP1189 Cyclamate Pattern 5.
  • FIG. 67 FT-IR Spectrum of AP1189 Besylate Pattern 1.
  • FIG. 68 FT-IR Spectrum of AP1189 Oxalate Pattern 1.
  • FIG. 69 FT-IR Spectrum of AP1189 Oxalate Pattern 2.
  • FIG. 70 FT-IR Spectrum of AP1189 Oxalate Pattern 4.
  • FIG. 71 FT-IR Spectrum of AP1189 (+)-Camphor-10-sulfonic acid Pattern 1.
  • FIG. 72 FT-IR Spectrum of AP1189 Oxoglutarate Pattern 1.
  • FIG. 73 FT-IR Spectrum of AP1189 DL-mandelic acid Pattern 2.
  • FIG. 74 FT-IR Spectrum of AP1189 DL-mandelic acid Pattern 3.
  • FIG. 75 FT-IR Spectrum of AP1189 Hippuric acid Pattern 1.
  • FIG. 76 FT-IR Spectrum of AP1189 Formic acid Pattern 1.
  • FIG. 77 FT-IR Spectrum of AP1189 DL-Lactic acid Pattern 1.
  • FIG. 78 FT-IR Spectrum of AP1189 DL-Lactic acid Pattern 1.
  • FIG. 79 FT-IR Spectrum of AP1189 Glutaric acid Pattern 1.
  • FIG. 80 FT-IR Spectrum of AP1189 Glutaric acid Pattern 2.
  • FIG. 81 TG/DSC thermogram of AP1189 Napadisylate Pattern 2. Weight Loss: 0.157 mg. Weight Percent Loss: 7.940%.
  • FIG. 82 TG/DSC thermogram of AP1189 Edisylate Pattern 1. Weight Loss: 0.082 mg. Weight Percent Loss: 4.634%. Enthalpy (normalised): 3.2707 J/g; Onset x: 69.98° C.; Peak temperature: 78.37° C. Enthalpy (normalised): 0.83635 J/g; Peak temperature: 151.31° C.
  • FIG. 83 TG/DSC thermogram of AP1189 Cyclamate Pattern 5. Weight Loss: 0.070 mg. Weight Percent Loss: 1.696%. Enthalpy (normalised): 0.68855 J/g; Onset x: 140.91° C.; Peak temperature: 146.39° C.
  • FIG. 84 TG/DSC thermogram of AP1189 Formic acid Pattern 1. Weight Loss: 0.008 mg. Weight Percent Loss: 3.049%. Enthalpy (normalised): 7.5282 J/g; Onset x: 169.12° C.; Peak temperature: 171.97° C.
  • FIG. 85 TG/DSC thermogram of AP1189 DL-Lactic acid Pattern 1. Weight Loss: 0.026 mg. Weight Percent Loss: 0.859%. Enthalpy (normalised): 31.499 J/g. Onset x: 189.47° C. Peak temperature: 192.80° C.
  • FIG. 86 TG/DSC thermogram of AP1189 DL-Lactic acid Pattern 1. Weight Loss: 0.034 mg. Weight Percent Loss: 1.476%. Enthalpy (normalised): 2.2523 J/g; Onset x: 198.48° C.; Peak temperature: 200.63° C.
  • FIG. 87 TG/DSC thermogram of AP1189 Glutaric acid Pattern 1. Weight Loss: 0.27 mg. Weight Percent Loss: 1.256%. Enthalpy (normalised): 0.0964 J/g; Onset x: 109.24° C.; Peak temperature: 115.31° C. Enthalpy (normalised): 16.647 J/g; Onset x: 159.93° C.; Peak temperature: 164.02° C.
  • FIG. 88 TG/DSC thermogram of AP1189 Glutaric acid Pattern 2. Weight Loss: 0.019 mg. Weight Percent Loss: 1.001%. Enthalpy (normalised): 48.550 J/g; Onset x: 162.77° C.; Peak temperature: 165.94° C.
  • FIG. 89 TG/DSC thermogram of AP1189 Glutaric acid Pattern 4. Weight Loss: 0.010 mg. Weight Percent Loss: 1.764%. Enthalpy (normalised): 18.475 J/g; Onset x: 114.55° C.; Peak temperature: 148.15° C. Enthalpy (normalised): 10.102 J/g; Onset x: 160.45° C.; Peak temperature: 163.28° C.
  • FIG. 90 TG/DSC thermogram of AP1189 Adipic acid Pattern 1. Weight Loss: 0.015 mg. Weight Percent Loss: 6.117%. Enthalpy (normalised): 12.428 J/g. Onset x: 183.34° C.; Peak temperature: 187.98° C.
  • FIG. 91 XRPD Diffractogram of AP1189 Glutaric acid Pattern 4.
  • FIG. 92 IR spectrum of AP1189 acetate Pattern 1.
  • the term “AP1189” may refer to either the free base structure of Formula I or it may refer to the acetate salt of AP1189.
  • the term “AP1189 free base” refers to the structure of Formula I.
  • the term “AP1189 acetate” refers to the acetate salt of the structure of Formula I.
  • SP1189 refers to the succinate salt of the structure of Formula I.
  • SP1189 and AP1189 succinate are synonymous as used herein.
  • N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetic acid then the non-protonated form is meant of that compound, e.g. “N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine acetic acid” is meant.
  • the compound of the disclosure N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine, including tautomers and stereoisomers thereof.
  • the compound of the disclosure is N- ⁇ (1E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine, including tautomers and stereoisomers thereof.
  • the compound of the disclosure is N′′-[(E)-[3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, including tautomers and stereoisomers thereof.
  • the compound of the disclosure is N- ⁇ (2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine, including tautomers and stereoisomers thereof.
  • the compound of the disclosure is N′′-[[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, including tautomers and stereoisomers thereof.
  • the compound of the disclosure is N- ⁇ (1E,2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine (also termed (E)-N-trans- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine herein)), including tautomers thereof.
  • the compound of the disclosure is N′′-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine, including tautomers thereof.
  • the compound of the disclosure is selected from the group consisting of 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, and N- ⁇ (1E,2Z)-3-[1-
  • the compound of the disclosure is selected from the group consisting of 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)-[(2Z)-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-
  • the alkene moiety of the compound is in the E configuration, and the imine moiety is in the Z or the E configuration.
  • 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.
  • the compound of the disclosure may additionally be any tautomer of the above structures.
  • tautomer means other structural isomers that exist in equilibrium resulting from the migration of a hydrogen atom.
  • the method of measuring the value inherently comprises some degree of uncertainty. For example, measurements of 2-theta values may have an uncertainty of 0.2°.
  • a crystalline “Form A” of AP1189 acetate is meant the crystalline form of AP1189 acetate that exhibits the X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation corresponding to AP1189 acetate Pattern 1 as disclosed herein.
  • a crystalline “Form B” of AP1189 succinate is meant the crystalline form of AP1189 succinate that exhibits the X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation corresponding to AP1189 succinate Pattern 1 as disclosed herein.
  • the unit of 2-theta values is degrees (°).
  • onset temperature is meant the designed intersection point of the extrapolated baseline and the inflectional tangent at the beginning of the melting.
  • seeding refers to the technique of adding a “seed” crystal to the crystallization solution to promote the formation of crystals.
  • the composition of the seed crystal is the same as the composition of the crystals being formed.
  • the present disclosure provides the compound AP1189, specifically a salt thereof.
  • One embodiment provides for the compound AP1189, including tautomeric forms thereof and/or isomeric forms thereof, such as enantiomeric forms and/or diastereomeric forms thereof.
  • the diastereomeric forms comprise cis and trans forms of the compound, specifically 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.
  • E configuration is synonymous to trans configuration
  • Z configuration is synonymous to cis configuration.
  • both of the atoms forming part of a double bond are each bound to exactly 1 further moiety that is not a hydrogen moiety or a lone pair.
  • One embodiment of the present disclosure provides for the acetate salt of AP1189.
  • Another embodiment of the present disclosure provides for the succinate salt of AP1189.
  • the term “compound of the disclosure” means the crystalline Form A of AP1189 acetate.
  • the term “compound of the disclosure” means the crystalline Form B of AP1189 succinate.
  • the pharmaceutically acceptable salt of AP1189 is selected from the group consisting of:
  • a pharmaceutically acceptable salt of AP1189 is selected from the group consisting of the acetate salt of AP1189, the succinate salt of AP1189, the DL-mandelic acid salt of AP1189, the hippuric acid salt of AP1189, the L-lactic acid salt of AP1189, the besylate salt of AP1189, the oxoglutarate salt of AP1189, the formic acid salt of AP1189, the DL-lactic acid salt of AP1189, the glutaric acid salt of AP1189, the adipic acid salt of AP1189 and the nitrate salt of AP1189.
  • One embodiment provides for a salt of AP1189 selected from the group consisting of:
  • treatment refers to the management and care of a subject for the purpose of combating a condition, disease or disorder.
  • the term is intended to include the full spectrum of treatments for a given condition from which the subject is suffering.
  • the subject to be treated is preferably a mammal, in particular a human being.
  • Treatment of animals, such as mice, rats, dogs, cats, horses, cows, sheep and pigs, is, however, also within the scope of the present context.
  • the subjects to be treated can be of various ages.
  • an oral formulation as disclosed herein comprising a crystalline form of an AP1189 salt disclosed herein, for use in the treatment of a disease or disorder in a subject, wherein the subject to be treated is a mammal.
  • the mammal is a human being.
  • the mammal is a domestic animal.
  • the mammal is selected from the group consisting of mice, rats, dogs, cats, horses, cows, sheep and pigs.
  • the present disclosure relates to crystalline forms of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salts. It is an object of the disclosure to provide crystalline forms of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salts having high solubility in aqueous medium, particularly at low pH.
  • Crystalline forms of AP1189 and salts thereof may be characterised by X-Ray Powder Diffraction (XRPD) analysis.
  • XRPD X-Ray Powder Diffraction
  • Such analysis may be carried out using a suitable X-ray powder diffractometer such as a PANalytical X'pert pro with PIXcel detector (128 channels). Scanning of samples may be performed between 3 and 35° 2 ⁇ . Samples may be gently ground prior to measurement to release any agglomerates. Samples may be loaded onto a multi-well plate with Kapton or Mylar polymer film to support the sample.
  • Table 1 shows an overview of the polymorphs disclosed herein
  • the present disclosure provides for a crystalline Form A of AP1189 acetate.
  • Crystalline Form A of AP1189 acetate exhibits an XRPD diffractogram as shown in FIG. 1 .
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 11.5 ⁇ 0.2, 23.5 ⁇ 0.2, and 27.0 ⁇ 0.2.
  • One embodiment provides for a crystalline Form A of AP1189 acetate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 1 .
  • One embodiment of the disclosure provides for a crystalline Form A of AP1189 acetate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form A of AP1189 acetate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 21.8 ⁇ 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.
  • one embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 2.
  • AP1189 acetate Another crystalline form of AP1189 acetate has been identified herein which exhibits a mixture of a XRPD Pattern 1 and XRPD Pattern 2.
  • the crystalline Form A of AP1189 acetate is substantially free of the polymorph of AP1189 acetate, which gives rise to XRPD Pattern 2.
  • “substantially free” means that the crystalline Form A of AP1189 acetate comprises less than 90% of the polymorph of AP1189 acetate which gives rise to XRPD Pattern 2, such as less than 80%, such as less than 70%, such as less than 60%, such as less than 50%, such as less than 40%, such as less than 30%, such as less than 20%, such as less than 15%, such as less than 10%, such as less than 5% of the polymorph of AP1189 acetate, which gives rise to XRPD Pattern 2.
  • the content of the polymorph of AP1189 acetate, which gives rise to XRPD Pattern 2 may be assessed by the intensity of X-ray lines of Pattern 2 relative to the intensity of the X-ray lines of Pattern 1 of AP1189 acetate.
  • Pattern 2 exhibits X-ray lines at (2-theta values) 14.9, 18.0, and 24.2 which do not overlap with X-ray lines originating from Pattern 1 of AP1189.
  • one embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate substantially free of a second crystalline form of AP1189 acetate, the second crystalline form of AP1189 acetate exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.9 ⁇ 0.2, 18.0 ⁇ 0.2, and/or 24.2 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate substantially free of a second crystalline form of AP1189 acetate, the second crystalline form of AP1189 acetate exhibits X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.9, 18.0, and/or 24.2.
  • the crystalline Form A of AP1189 acetate exhibits no X-ray lines at 14.9 ⁇ 0.2, 18.0 0.2, and/or 24.2 ⁇ 0.2 in an powder diffraction pattern, or the crystalline Form A of AP1189 acetate exhibits lines at 14.9 ⁇ 0.2, 18.0 ⁇ 0.2, and/or 24.2 ⁇ 0.2 that have a relative intensity less than 30%, such as less than 25%, such as less than 20%, such as less than 15%, such as less than 10%, such as less than 5%.
  • the present disclosure provides for a crystalline Form B of AP1189 succinate.
  • Crystalline Form B of AP1189 succinate exhibits an XRPD diffractogram as shown in FIG. 6 .
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 9.7 ⁇ 0.2, 22.8 ⁇ 0.2, and 26.7 ⁇ 0.2.
  • One embodiment provides for a crystalline Form B of AP1189 succinate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.4 ⁇ 0.2, 13.4 ⁇ 0.2, 16.3 ⁇ 0.2, and 19.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.2 ⁇ 0.2, 15.8 ⁇ 0.2, 21.8 ⁇ 0.2, and 28.5 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form B of AP1189 succinate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 6 .
  • One embodiment of the disclosure provides for a crystalline Form B of AP1189 succinate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form B of AP1189 succinate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 7.
  • One embodiment provides for crystalline forms of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate, which may be converted to AP1189 acetate of crystalline Form A.
  • One embodiment provides for a crystalline Form I of AP1189 acetate corresponding to XRPD Pattern 1 and 2.
  • a specific embodiment provides for a crystalline Form I of AP1189 acetate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ 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.
  • One embodiment provides for a crystalline Form I of AP1189 acetate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation as shown in FIG. 2 .
  • One embodiment of the present disclosure provides for a crystalline Form II of AP1189 acetate corresponding to XRPD Pattern 3.
  • a specific embodiment provides for a crystalline Form II of AP1189 acetate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ 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.
  • One embodiment provides for a crystalline Form II of AP1189 acetate exhibiting X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation as shown in FIG. 3 .
  • One embodiment of the present disclosure provides for a solid form of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate.
  • One embodiment of the present disclosure provides for a solid, amorphous form of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate.
  • the disclosure also provides for a crystalline Form C of AP1189 tosylate.
  • Crystalline Form C of AP1189 tosylate exhibits an XRPD diffractogram as shown in FIG. 4 .
  • One embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.5 ⁇ 0.2, 21.0 ⁇ 0.2, and 25.2 ⁇ 0.2.
  • the crystalline Form C of AP1189 tosylate further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 13.4 ⁇ 0.2 and 16.0 ⁇ 0.2. In one embodiment of the present disclosure, the crystalline Form C of AP1189 tosylate further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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. In one embodiment, the crystalline Form C of AP1189 tosylate exhibits an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 4 .
  • One embodiment of the disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 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.
  • one embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 8.0 ⁇ 0.2, 9.4 ⁇ 0.2, 10.0 0.2, 13.4 ⁇ 0.2, 14.5 ⁇ 0.2, 15.3 ⁇ 0.2, 16.0 ⁇ 0.2, 16.7 ⁇ 0.2, 17.6 ⁇ 0.2, 19.2 ⁇ 0.2, 19.8 ⁇ 0.2, 21.0 ⁇ 0.2, 21.3 ⁇ 0.2, 25.2 ⁇ 0.2, and 25.4 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 5.
  • the disclosure also provides for a crystalline Form D of AP1189 fumarate.
  • Crystalline Form D of AP1189 fumarate exhibits an XRPD diffractogram as shown in FIG. 5 .
  • One embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 17.6 ⁇ 0.2, 21.2 ⁇ 0.2, and 26.3 ⁇ 0.2.
  • the crystalline Form D of AP1189 fumarate further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.5 ⁇ 0.2, 21.9 ⁇ 0.2, and 23.9 ⁇ 0.2. In one embodiment of the present disclosure, the crystalline Form D of AP1189 fumarate further exhibits one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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. In one embodiment, the crystalline Form D of AP1189 fumarate exhibits an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 5 .
  • One embodiment of the disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 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.
  • One embodiment of the disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 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,
  • one embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.2 ⁇ 0.2, 10.5 ⁇ 0.2, 10.9 ⁇ 0.2, 11.5 ⁇ 0.2, 11.9 ⁇ 0.2, 15.8 ⁇ 0.2, 17.6 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 21.2 ⁇ 0.2, 21.9 ⁇ 0.2, 23.4 ⁇ 0.2, 23.9 ⁇ 0.2, 24.5 ⁇ 0.2, 26.3 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 6.
  • the present disclosure provides for a crystalline Form III of AP1189 napadisylate.
  • Crystalline Form III of AP1189 napadisylate exhibits an XRPD diffractogram as shown in FIG. 14 .
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 13.4 ⁇ 0.2, 22.2 ⁇ 0.2, and 26.8 ⁇ 0.2.
  • One embodiment provides for a crystalline Form III of AP1189 napadisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 15.1 ⁇ 0.2, 15.5 ⁇ 0.2, 23.5 ⁇ 0.2, and 28.0 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 7.6 ⁇ 0.2, 10.7 ⁇ 0.2, 12.4 ⁇ 0.2, and 22.8 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 14 .
  • One embodiment of the disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • embodiment of the disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 9.
  • the present disclosure provides for a crystalline Form IV of AP1189 napadisylate.
  • Crystalline Form IV of AP1189 napadisylate exhibits an XRPD diffractogram as shown in FIG. 15 .
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 5.4 ⁇ 0.2, 15.6 ⁇ 0.2, and 23.4 ⁇ 0.2.
  • One embodiment provides for a crystalline Form IV of AP1189 napadisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 18.4 ⁇ 0.2, 22.0 0.2, 24.2 ⁇ 0.2, and 25.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 15 .
  • One embodiment of the disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.4, 8.5, 10.8, 12.6, 13.1, 15.6, 18.4, 19.5, 19.9, 21.1, 22.0, 22.7, 23.4, 24.2, 25.2, and 25.8.
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.4 ⁇ 0.2, 8.5 ⁇ 0.2, 10.8 ⁇ 0.2, 12.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15.6 ⁇ 0.2, 18.4 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 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, and 25.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 10.
  • the present disclosure provides for a crystalline Form V of AP1189 esylate.
  • Crystalline Form V of AP1189 esylate exhibits an XRPD diffractogram as shown in FIG. 16 .
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.5 ⁇ 0.2, 16.5 ⁇ 0.2, and 18.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form V of AP1189 esylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.8 ⁇ 0.2, 19.7 ⁇ 0.2, 20.1 ⁇ 0.2, and 26.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form V of AP1189 esylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 16 .
  • One embodiment of the disclosure provides for a crystalline Form V of AP1189 esylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form V of AP1189 esylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 8.5 ⁇ 0.2, 9.8 ⁇ 0.2, 10.4 ⁇ 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, 21.9 ⁇ 0.2, 22.5 ⁇ 0.2, 26.1 ⁇ 0.2, and 26.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 11.
  • the present disclosure provides for a crystalline Form VI of AP1189 edisylate.
  • Crystalline Form VI of AP1189 edisylate exhibits an XRPD diffractogram as shown in FIG. 17 .
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 4.8 ⁇ 0.2, 12.8 ⁇ 0.2, and 16.5 ⁇ 0.2.
  • One embodiment provides for a crystalline Form VI of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 17.9 ⁇ 0.2, 21.4 ⁇ 0.2, 23.4 ⁇ 0.2, and 27.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 17 .
  • One embodiment of the disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 12.
  • the present disclosure provides for a crystalline Form VII of AP1189 edisylate.
  • Crystalline Form VII of AP1189 edisylate exhibits an XRPD diffractogram as shown in FIG. 18 .
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 6.1 ⁇ 0.2, 15.7 ⁇ 0.2, and 23.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form VII of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.1, 20.1 ⁇ 0.2, and 21.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.7 ⁇ 0.2, 12.7 ⁇ 0.2, and 19.3 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 18 .
  • One embodiment of the disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 13.
  • the present disclosure provides for a crystalline Form VIII of AP1189 edisylate.
  • Crystalline Form VIII of AP1189 edisylate exhibits an XRPD diffractogram as shown in FIG. 19 .
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 15.5 ⁇ 0.2, 20.7 ⁇ 0.2, and 21.7 ⁇ 0.2.
  • One embodiment provides for a crystalline Form VIII of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.1 ⁇ 0.2, 13.0 ⁇ 0.2, and 24.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.4 ⁇ 0.2 and 25.2 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 19 .
  • One embodiment of the disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • one embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.4, 12.1, 13.0, 15.5, 20.7, 21.7, 24.1, and 25.2.
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 14.
  • the present disclosure provides for a crystalline Form IX of AP1189 edisylate.
  • Crystalline Form IX of AP1189 edisylate exhibits an XRPD diffractogram as shown in FIG. 20 .
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 4.5 ⁇ 0.2, 16.7 ⁇ 0.2, and 24.7 ⁇ 0.2.
  • One embodiment provides for a crystalline Form IX of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.2 ⁇ 0.2 and 15.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.0 ⁇ 0.2 and 18.0.
  • One embodiment of the disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 20 .
  • One embodiment of the disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 4.5 ⁇ 0.2, 9.0 ⁇ 0.2, 11.7 ⁇ 0.2, 12.2 ⁇ 0.2, 12.4 ⁇ 0.2, 13.1 ⁇ 0.2, 15.5 ⁇ 0.2, 16.7 ⁇ 0.2, 17.3 ⁇ 0.2, 18.0 ⁇ 0.2, 19.9 ⁇ 0.2, 20.4 ⁇ 0.2, 21.1 ⁇ 0.2, 22.0 ⁇ 0.2, 22.9 ⁇ 0.2, 24.7 ⁇ 0.2, 26.8 ⁇ 0.2, and 28.3 ⁇ 0.2.
  • one embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 4.5, 9.0, 12.2, 15.5, 16.7, 18.0, and 24.7.
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 15.
  • the present disclosure provides for a crystalline Form X of AP1189 nitrate.
  • Crystalline Form X of AP1189 nitrate exhibits an XRPD diffractogram as shown in FIG. 21 .
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 15.3 ⁇ 0.2, 21.4 ⁇ 0.2, and 25.1 ⁇ 0.2.
  • One embodiment provides for a crystalline Form X of AP1189 nitrate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.9 ⁇ 0.2, 12.5 ⁇ 0.2, and 27.7 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 21 .
  • One embodiment of the disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 3.7 ⁇ 0.2, 7.5 ⁇ 0.2, 11.9 ⁇ 0.2, 12.5 ⁇ 0.2, 13.1 ⁇ 0.2, 14.7 ⁇ 0.2, 15.3 ⁇ 0.2, 16.9 ⁇ 0.2, 17.7 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.6 ⁇ 0.2, 21.4 ⁇ 0.2, 23.0 ⁇ 0.2, 24.1 ⁇ 0.2, 25.1 ⁇ 0.2, 26.6 ⁇ 0.2, 27.7 ⁇ 0.2, 29.5 ⁇ 0.2, and 31.7 ⁇ 0.2.
  • one embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 16.
  • the present disclosure provides for a crystalline Form XI of AP1189 cyclamate.
  • Crystalline Form XI of AP1189 cyclamate exhibits an XRPD diffractogram as shown in FIG. 22 .
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 7.0 ⁇ 0.2, 13.8 ⁇ 0.2, and 15.7 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XI of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 15.3 ⁇ 0.2, 20.7 ⁇ 0.2, and 21.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 3.2 ⁇ 0.2, 11.3 ⁇ 0.2, and 21.8 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 22 .
  • One embodiment of the disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • one embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 17.
  • the present disclosure provides for a crystalline Form XII of AP1189 cyclamate. Crystalline Form XII of AP1189 cyclamate exhibits an XRPD diffractogram as shown in FIG. 23 .
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 7.3 ⁇ 0.2, 15.3 ⁇ 0.2, and 17.9 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XII of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 16.3 ⁇ 0.2, 19.1 ⁇ 0.2, 22.0 0.2, and 22.7 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.3 ⁇ 0.2, 13.1 ⁇ 0.2, and 16.9 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 23 .
  • One embodiment of the disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • one embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 18.
  • the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate.
  • Crystalline Form XIII of AP1189 cyclamate exhibits an XRPD diffractogram as shown in FIG. 24 .
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 15.3 ⁇ 0.2, 18.5 ⁇ 0.2, and 18.7 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XIII of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.4 ⁇ 0.2, 14.6 ⁇ 0.2, 16.7 ⁇ 0.2, and 19.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 24 .
  • One embodiment of the disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 20.2, 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.
  • One embodiment of the disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 20.2 ⁇ 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
  • one embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 19.
  • the present disclosure provides for a crystalline Form XIV of AP1189 besylate.
  • Crystalline Form XIV of AP1189 besylate exhibits an XRPD diffractogram as shown in FIG. 25 .
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 13.0 ⁇ 0.2, 15.1 ⁇ 0.2, and 19.9 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XIV of AP1189 besylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.2 ⁇ 0.2 and 18.3 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 8.3 ⁇ 0.2, 9.0 0.2, 16.4 ⁇ 0.2, and 18.7 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 25 .
  • One embodiment of the disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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 ⁇
  • crystalline Form XIV of AP1189 besylate by X-ray lines (2-theta values) having a high relative intensity, and/or by characteristic X-ray lines.
  • a crystalline Form XIV of AP1189 besylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 20.
  • the present disclosure provides for a crystalline Form XV of AP1189 oxalate.
  • Crystalline Form XV of AP1189 oxalate exhibits an XRPD diffractogram as shown in FIG. 26 .
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 19.5 ⁇ 0.2, 23.3 ⁇ 0.2, and 25.8 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XV of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 13.9 ⁇ 0.2, 15.6 ⁇ 0.2, and 23.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 7.2 ⁇ 0.2, 10.8 ⁇ 0.2, and 21.7 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 26 .
  • One embodiment of the disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 21.
  • the present disclosure provides for a crystalline Form XVI of AP1189 oxalate.
  • Crystalline Form XVI of AP1189 oxalate exhibits an XRPD diffractogram as shown in FIG. 27 .
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 17.1 ⁇ 0.2, 17.9 ⁇ 0.2, and 19.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XVI of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 15.9 ⁇ 0.2, 24.2 ⁇ 0.2, 24.4 ⁇ 0.2, and 27.3 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.5 ⁇ 0.2, 11.3 ⁇ 0.2, 21.2 ⁇ 0.2, and 25.4 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 27 .
  • One embodiment of the disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 23.4 ⁇ 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.
  • one embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.5, 11.3, 15.9, 17.1, 17.9, 19.6, 21.2, 24.2, 24.4, 25.4, and 27.3.
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 22.
  • the present disclosure provides for a crystalline Form XVII of AP1189 oxalate. Crystalline Form XVII of AP1189 oxalate exhibits an XRPD diffractogram as shown in FIG. 28 .
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 6.3 ⁇ 0.2, 10.6 ⁇ 0.2, and 19.8 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XVII of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 11.7 ⁇ 0.2, 12.3 ⁇ 0.2, 18.4 ⁇ 0.2, and 23.8 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 14.1 ⁇ 0.2, 23.5 ⁇ 0.2, and 30.0 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 28 .
  • One embodiment of the disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 22.0 ⁇ 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
  • one embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 23.
  • the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid. Crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibits an XRPD diffractogram as shown in FIG. 29 .
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 6.5 ⁇ 0.2, 11.5 ⁇ 0.2, and 14.8 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 13.0 ⁇ 0.2, 13.7 ⁇ 0.2, 16.1 ⁇ 0.2, and 21.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 15.9 ⁇ 0.2, 18.8 ⁇ 0.2, and 19.8 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 29 .
  • One embodiment of the disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 18.1 ⁇ 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.
  • one embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.5, 11.5, 13.0, 13.7, 14.8, 15.9, 16.1, 18.8, 19.8, and 21.1.
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 24.
  • the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate. Crystalline Form XIX of AP1189 oxoglutarate exhibits an XRPD diffractogram as shown in FIG. 30 .
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 16.8 ⁇ 0.2, 23.4 ⁇ 0.2, and 23.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XIX of AP1189 oxoglutarate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 13.4 ⁇ 0.2, 16.4 ⁇ 0.2, 21.6 ⁇ 0.2, and 26.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 30 .
  • One embodiment of the disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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
  • one embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.1, 10.7, 12.8, 13.2, 13.4, 16.4, 16.8, 20.8, 21.6, 23.4, 23.6, 24.1, 24.2, 26.5, and 26.9.
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.1 ⁇ 0.2, 10.7 ⁇ 0.2, 12.8 ⁇ 0.2, 13.2 ⁇ 0.2, 13.4 ⁇ 0.2, 16.4 ⁇ 0.2, 16.8 ⁇ 0.2, 20.8 ⁇ 0.2, 21.6 ⁇ 0.2, 23.4 ⁇ 0.2, 23.6 ⁇ 0.2, 24.1 ⁇ 0.2, 24.2 ⁇ 0.2, 26.5 ⁇ 0.2, and 26.9 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 25.
  • the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid. Crystalline Form XX of AP1189 DL-mandelic acid exhibits an XRPD diffractogram as shown in FIG. 31 .
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.8 ⁇ 0.2, 24.2 ⁇ 0.2, and 25.5 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XX of AP1189 DL-mandelic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.6 ⁇ 0.2, 10.0 ⁇ 0.2, 19.1 ⁇ 0.2, and 21.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 31 .
  • One embodiment of the disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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
  • one embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.3 ⁇ 0.2, 9.6 ⁇ 0.2, 10.0 ⁇ 0.2, 12.4 ⁇ 0.2, 13.3 ⁇ 0.2, 14.8 ⁇ 0.2, 16.0 ⁇ 0.2, 16.8 ⁇ 0.2, 17.9 ⁇ 0.2, 19.1 ⁇ 0.2, 21.2 ⁇ 0.2, 21.5 ⁇ 0.2, 24.2 ⁇ 0.2, 24.8 ⁇ 0.2, and 25.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 26.
  • the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid. Crystalline Form XXI of AP1189 DL-mandelic acid exhibits an XRPD diffractogram as shown in FIG. 32 .
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 5.4 ⁇ 0.2, 10.0 ⁇ 0.2, and 24.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXI of AP1189 further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.8 ⁇ 0.2, 16.6 ⁇ 0.2, 18.1 ⁇ 0.2, and 21.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.7 ⁇ 0.2, 13.5 ⁇ 0.2, 21.7 ⁇ 0.2, and 25.4 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 32 .
  • One embodiment of the disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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
  • one embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.4 ⁇ 0.2, 9.8 ⁇ 0.2, 10.0 ⁇ 0.2, 12.7 ⁇ 0.2, 13.5 ⁇ 0.2, 16.6 ⁇ 0.2, 18.1 ⁇ 0.2, 21.1 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, and 25.4 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 27.
  • the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid. Crystalline Form XXII of AP1189 hippuric acid exhibits an XRPD diffractogram as shown in FIG. 33 .
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 20.1 ⁇ 0.2, 24.1 ⁇ 0.2, and 24.5 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXII of AP1189 hippuric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.6 ⁇ 0.2, 14.1 ⁇ 0.2, and 15.5 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 33 .
  • One embodiment of the disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 9.6 ⁇ 0.2, 10.9 ⁇ 0.2, 11.5 ⁇ 0.2, 14.1 ⁇ 0.2, 14.4 ⁇ 0.2, 14.9 ⁇ 0.2, 15.5 ⁇ 0.2, 18.1 ⁇ 0.2, 20.1 ⁇ 0.2, 24.1 ⁇ 0.2, and 24.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 28.
  • the present disclosure provides for a crystalline Form XXIII of AP1189 formate.
  • Crystalline Form XXIII of AP1189 formate exhibits an XRPD diffractogram as shown in FIG. 34 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 13.3 ⁇ 0.2, 15.1 ⁇ 0.2, and 25.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXIII of AP1189 formate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 17.3 ⁇ 0.2, 18.9 ⁇ 0.2, 21.8 ⁇ 0.2, and 23.6 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.2 ⁇ 0.2, 20.6 ⁇ 0.2, 22.8 ⁇ 0.2, 28.9 ⁇ 0.2, and 29.2 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 34 .
  • One embodiment of the disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 22.8 ⁇ 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,
  • one embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.2 ⁇ 0.2, 13.3 ⁇ 0.2, 15.1 ⁇ 0.2, 17.3 ⁇ 0.2, 18.9 ⁇ 0.2, 20.6 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.6 ⁇ 0.2, 25.6 ⁇ 0.2, 28.9 ⁇ 0.2, and 29.2 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 29.
  • the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid.
  • Crystalline Form XXIV of AP1189 DL-lactic acid exhibits an XRPD diffractogram as shown in FIG. 35 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 3.8 ⁇ 0.2, 9.9 ⁇ 0.2, and 11.9 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXIV of AP1189 DL-lactic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 7.7 ⁇ 0.2, 23.0 ⁇ 0.2, and 27.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 15.4 ⁇ 0.2, 23.9 ⁇ 0.2, and 25.3 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 35 .
  • One embodiment of the disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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
  • one embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 30.
  • the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid. Crystalline Form XXV of AP1189 DL-lactic acid exhibits an XRPD diffractogram as shown in FIG. 36 .
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 9.8 ⁇ 0.2, 11.9 ⁇ 0.2, and 27.6 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXV of AP1189 DL-lactic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 3.8 ⁇ 0.2, 23.3 ⁇ 0.2, and 23.9 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 7.6 ⁇ 0.2, 15.3 ⁇ 0.2, and 25.6 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 36 .
  • One embodiment of the disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 31.
  • the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid. Crystalline Form XXVI of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in FIG. 37 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 8.3 ⁇ 0.2, 15.9 ⁇ 0.2, and 21.9 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXVI of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 12.8 ⁇ 0.2, 15.1 ⁇ 0.2, and 27.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG.
  • One embodiment of the disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 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
  • one embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 3.2, 8.3, 8.7, 12.8, 14.4, 15.1, 15.9, 16.2, 19.0, 19.8, 21.9, 27.1, 28.8, and 29.5.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 3.2 ⁇ 0.2, 8.3 ⁇ 0.2, 8.7 ⁇ 0.2, 12.8 ⁇ 0.2, 14.4 ⁇ 0.2, 15.1 ⁇ 0.2, 15.9 ⁇ 0.2, 16.2 ⁇ 0.2, 19.0 ⁇ 0.2, 19.8 ⁇ 0.2, 21.9 ⁇ 0.2, 27.1 ⁇ 0.2, 28.8 ⁇ 0.2, and 29.5 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 32.
  • the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid. Crystalline Form XXVII of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in FIG. 38 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.1 ⁇ 0.2, 21.7 ⁇ 0.2, and 25.0 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXVII of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ 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.
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 38 .
  • One embodiment of the disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 20.9, 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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, 20.9 ⁇ 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.
  • one embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.3, 10.1, 14.1, 14.3, 14.7, 15.1, 16.9, 17.4, 21.7, 22.1, 22.6, 25.0, 25.6, 26.5, 27.1, 28.2, and 28.7.
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.3 ⁇ 0.2, 10.1 ⁇ 0.2, 14.1 ⁇ 0.2, 14.3 ⁇ 0.2, 14.7 ⁇ 0.2, 15.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.4 ⁇ 0.2, 21.7 ⁇ 0.2, 22.1 ⁇ 0.2, 22.6 ⁇ 0.2, 25.0 ⁇ 0.2, 25.6 ⁇ 0.2, 26.5 ⁇ 0.2, 27.1 ⁇ 0.2, 28.2 ⁇ 0.2, and 28.7 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 33.
  • the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid. Crystalline Form XXVIII of AP1189 glutaric acid exhibits an XRPD diffractogram as shown in FIG. 91 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 14.2 ⁇ 0.2, 16.9 ⁇ 0.2, and 24.5 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXVIII of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.3 ⁇ 0.2, 15.2 ⁇ 0.2, 20.9 ⁇ 0.2, and 21.9 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 91 .
  • One embodiment of the disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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
  • one embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.3, 8.9, 10.1, 12.6, 14.2, 15.2, 16.9, 17.4, 19.1, 20.6, 20.9, 21.9, 24.5, and 28.4.
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 6.3 ⁇ 0.2, 8.9 ⁇ 0.2, 10.1 ⁇ 0.2, 12.6 ⁇ 0.2, 14.2 ⁇ 0.2, 15.2 ⁇ 0.2, 16.9 ⁇ 0.2, 17.4 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.9 ⁇ 0.2, 24.5 ⁇ 0.2, and 28.4 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 34.
  • the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid. Crystalline Form XXIX of AP1189 adipic acid exhibits an XRPD diffractogram as shown in FIG. 39 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation at 13.4 ⁇ 0.2, 14.5 ⁇ 0.2, and 25.5 ⁇ 0.2.
  • One embodiment provides for a crystalline Form XXIX of AP1189 adipic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 17.6 ⁇ 0.2, 23.5 ⁇ 0.2, 25.4 ⁇ 0.2, and 27.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid further exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.2 ⁇ 0.2, 19.2 ⁇ 0.2, and 21.4 ⁇ 0.2.
  • One embodiment of the disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting an X-ray pattern (2-theta values) in a powder diffraction when measured using Cu K ⁇ radiation according to FIG. 39 .
  • One embodiment of the disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation 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.
  • One embodiment of the disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 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.
  • one embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.2, 13.4, 14.5, 17.6, 19.2, 21.4, 23.5, 25.4, 25.5, and 27.1.
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of 5.2 ⁇ 0.2, 13.4 ⁇ 0.2, 14.5 ⁇ 0.2, 17.6 ⁇ 0.2, 19.2 ⁇ 0.2, 21.4 ⁇ 0.2, 23.5 ⁇ 0.2, 25.4 ⁇ 0.2, 25.5 ⁇ 0.2, and 27.1 ⁇ 0.2.
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic exhibiting one or more X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu K ⁇ radiation selected from the group consisting of the 2-theta values in listed in Table 35.
  • the salts of AP1189 provided herein may be further characterised by the onset temperatures they exhibit as assessed by differential scanning calorimetry.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting in differential scanning calorimetry an onset temperature between 185 and 199° C.
  • One specific embodiment of the present disclosure provides a crystalline Form A of AP1189 acetate exhibiting in differential scanning calorimetry an onset temperature of substantially 192° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form A of AP1189 acetate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 8 .
  • One embodiment of the present disclosure provides a crystalline Form A of AP1189 acetate exhibiting a differential scanning calorimetry thermogram according to FIG. 8 .
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 192 ⁇ 7° C., such as 192 ⁇ 6° C., such as 192 ⁇ 5° C., such as 192 ⁇ 4° C., such as 192 ⁇ 3° C., such as 192 ⁇ 2° C., such as 192 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting in differential scanning calorimetry an onset temperature between 187 and 201° C.
  • One specific embodiment of the present disclosure provides a crystalline Form B of AP1189 succinate exhibiting in differential scanning calorimetry an onset temperature of substantially 194° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form B of AP1189 succinate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 13 .
  • One embodiment of the present disclosure provides a crystalline Form B of AP1189 succinate exhibiting a differential scanning calorimetry thermogram according to FIG. 13 .
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 195 ⁇ 7° C., such as 195 ⁇ 6° C., such as 195 ⁇ 5° C., such as 1954° C., such as 1953° C., such as 195 ⁇ 2° C., such as 195 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting in differential scanning calorimetry an onset temperature between 227 and 241° C.
  • One specific embodiment of the present disclosure provides a crystalline Form C of AP1189 tosylate exhibiting in differential scanning calorimetry an onset temperature of substantially 234° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 11 .
  • One embodiment of the present disclosure provides a crystalline Form C of AP1189 tosylate exhibiting a differential scanning calorimetry thermogram according to FIG. 11 .
  • One embodiment of the present disclosure provides for a crystalline Form C of AP1189 tosylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 234 ⁇ 7° C., such as 234 ⁇ 6° C., such as 234 ⁇ 5° C., such as 234 ⁇ 4° C., such as 234 ⁇ 3° C., such as 234 ⁇ 2° C., such as 234 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting in differential scanning calorimetry an onset temperature between 208 and 222° C.
  • One specific embodiment of the present disclosure provides a crystalline Form D of AP1189 fumarate exhibiting in differential scanning calorimetry an onset temperature of substantially 215° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 12 .
  • One embodiment of the present disclosure provides a crystalline Form D of AP1189 fumarate exhibiting a differential scanning calorimetry thermogram according to FIG. 12 .
  • One embodiment of the present disclosure provides for a crystalline Form D of AP1189 fumarate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 215 ⁇ 7° C., such as 215 ⁇ 6° C., such as 215 ⁇ 5° C., such as 215 ⁇ 4° C., such as 215 ⁇ 3° C., such as 215 ⁇ 2° C., such as 215 ⁇ 1° C.
  • Certain salts disclosed herein exhibit more than one onset temperature, e.g. two onset temperatures.
  • the salts may be characterised by either of their onset temperatures in isolation, or as a combination of onset temperatures.
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature between 80 and 94° C.
  • One specific embodiment of the present disclosure provides a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 87° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 40 .
  • One embodiment of the present disclosure provides a crystalline Form III of AP1189 napadisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 40 .
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 87 ⁇ 7° C., such as 87 ⁇ 6° C., such as 87 ⁇ 5° C., such as 874° C., such as 873° C., such as 87 ⁇ 2° C., such as 87 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature between 180 and 194° C.
  • One specific embodiment of the present disclosure provides a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 187° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 40 .
  • One embodiment of the present disclosure provides a crystalline Form III of AP1189 napadisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 40 .
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 187 ⁇ 7° C., such as 187 ⁇ 6° C., such as 187 ⁇ 5° C., such as 187 ⁇ 4° C., such as 187 ⁇ 3° C., such as 187 ⁇ 2° C., such as 187 ⁇ 1° C.
  • One embodiment of the disclosure provides for a crystalline Form IV of AP1189 napadisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 81 .
  • One embodiment of the present disclosure provides a crystalline Form IV of AP1189 napadisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 81 .
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting in differential scanning calorimetry an onset temperature between 200 and 214° C.
  • One specific embodiment of the present disclosure provides a crystalline Form V of AP1189 esylate exhibiting in differential scanning calorimetry an onset temperature of substantially 207° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form V of AP1189 esylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 41 .
  • One embodiment of the present disclosure provides a crystalline Form V of AP1189 esylate exhibiting a differential scanning calorimetry thermogram according to FIG. 41 .
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 207 ⁇ 7° C., such as 207 ⁇ 6° C., such as 207 ⁇ 5° C., such as 207 ⁇ 4° C., such as 207 ⁇ 3° C., such as 207 ⁇ 2° C., such as 207 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 71 and 85° C.
  • One specific embodiment of the present disclosure provides a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 78° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 82 .
  • One embodiment of the present disclosure provides a crystalline Form VI of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 82 .
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 78 ⁇ 7° C., such as 78 ⁇ 6° C., such as 78 ⁇ 5° C., such as 78 ⁇ 4° C., such as 78 ⁇ 3° C., such as 78 ⁇ 2° C., such as 78 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 144 and 158° C.
  • One specific embodiment of the present disclosure provides a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 151° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 82 .
  • One embodiment of the present disclosure provides a crystalline Form VI of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 82 .
  • One embodiment of the present disclosure provides for a crystalline Form VI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 151 ⁇ 7° C., such as 151 ⁇ 6° C., such as 151 ⁇ 5° C., such as 151 ⁇ 4° C., such as 151 ⁇ 3° C., such as 151 ⁇ 2° C., such as 151 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 218 and 232° C.
  • One specific embodiment of the present disclosure provides a crystalline Form VII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 225° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 42 .
  • One embodiment of the present disclosure provides a crystalline Form VII of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 42 .
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 225 ⁇ 7° C., such as 225 ⁇ 6° C., such as 225 ⁇ 5° C., such as 225 ⁇ 4° C., such as 225 ⁇ 3° C., such as 225 ⁇ 2° C., such as 225 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 201 and 215° C.
  • One specific embodiment of the present disclosure provides a crystalline Form VIII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 208° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 43 .
  • One embodiment of the present disclosure provides a crystalline Form VIII of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 43 .
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 208 ⁇ 7° C., such as 208 ⁇ 6° C., such as 208 ⁇ 5° C., such as 208 ⁇ 4° C., such as 208 ⁇ 3° C., such as 208 ⁇ 2° C., such as 208 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 52 and 66° C.
  • One specific embodiment of the present disclosure provides a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 59° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 44 .
  • One embodiment of the present disclosure provides a crystalline Form IX of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 44 .
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 59 ⁇ 7° C., such as 59 ⁇ 6° C., such as 59 ⁇ 5° C., such as 59 ⁇ 4° C., such as 59 ⁇ 3° C., such as 59 ⁇ 2° C., such as 59 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature between 144 and 158° C.
  • One specific embodiment of the present disclosure provides a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature of substantially 151° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 44 .
  • One embodiment of the present disclosure provides a crystalline Form IX of AP1189 edisylate exhibiting a differential scanning calorimetry thermogram according to FIG. 44 .
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 151 ⁇ 7° C., such as 151 ⁇ 6° C., such as 151 ⁇ 5° C., such as 151 ⁇ 4° C., such as 151 ⁇ 3° C., such as 151 ⁇ 2° C., such as 151 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting in differential scanning calorimetry an onset temperature between 172 and 186° C.
  • One specific embodiment of the present disclosure provides a crystalline Form X of AP1189 nitrate exhibiting in differential scanning calorimetry an onset temperature of substantially 179° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 45 .
  • One embodiment of the present disclosure provides a crystalline Form X of AP1189 nitrate exhibiting a differential scanning calorimetry thermogram according to FIG. 45 .
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 179 ⁇ 7° C., such as 179 ⁇ 6° C., such as 179 ⁇ 5° C., such as 179 ⁇ 4° C., such as 179 ⁇ 3° C., such as 179 ⁇ 2° C., such as 179 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature between 123 and 137° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XI of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature of substantially 130° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 46 .
  • One embodiment of the present disclosure provides a crystalline Form XI of AP1189 cyclamate exhibiting a differential scanning calorimetry thermogram according to FIG. 46 .
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 130 ⁇ 7° C., such as 130 ⁇ 6° C., such as 130 ⁇ 5° C., such as 130 ⁇ 4° C., such as 130 ⁇ 3° C., such as 130 ⁇ 2° C., such as 130 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature between 131 and 145° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature of substantially 138° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 47 .
  • One embodiment of the present disclosure provides a crystalline Form XII of AP1189 cyclamate exhibiting a differential scanning calorimetry thermogram according to FIG. 47 .
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 138 ⁇ 7° C., such as 138 ⁇ 6° C., such as 138 ⁇ 5° C., such as 138 ⁇ 4° C., such as 138 ⁇ 3° C., such as 138 ⁇ 2° C., such as 138 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature between 134 and 148° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XIII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature of substantially 141° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 83 .
  • One embodiment of the present disclosure provides a crystalline Form XIII of AP1189 cyclamate exhibiting a differential scanning calorimetry thermogram according to FIG. 83 .
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 141 ⁇ 7° C., such as 141 ⁇ 6° C., such as 141 ⁇ 5° C., such as 141 ⁇ 4° C., such as 141 ⁇ 3° C., such as 141 ⁇ 2° C., such as 141 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting in differential scanning calorimetry an onset temperature between 219 and 223° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XIV of AP1189 besylate exhibiting in differential scanning calorimetry an onset temperature of substantially 216° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 48 .
  • One embodiment of the present disclosure provides a crystalline Form XIV of AP1189 besylate exhibiting a differential scanning calorimetry thermogram according to FIG. 48 .
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 216 ⁇ 7° C., such as 216 ⁇ 6° C., such as 216 ⁇ 5° C., such as 216 ⁇ 4° C., such as 216 ⁇ 3° C., such as 216 ⁇ 2° C., such as 216 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting in differential scanning calorimetry a peak temperature between 204 and 218° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XV of AP1189 oxalate exhibiting in differential scanning calorimetry a peal temperature of substantially 211° C.
  • the peak temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting in differential scanning calorimetry a peak temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 49 .
  • One embodiment of the present disclosure provides a crystalline Form XV of AP1189 oxalate exhibiting a differential scanning calorimetry thermogram according to FIG. 49 .
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate exhibiting in differential scanning calorimetry a peak temperature falling within the interval 211 ⁇ 7° C., such as 211 ⁇ 6° C., such as 211 ⁇ 5° C., such as 211 ⁇ 4° C., such as 211 ⁇ 3° C., such as 211 ⁇ 2° C., such as 211 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting in differential scanning calorimetry an onset temperature between 200 and 214° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XVI of AP1189 oxalate exhibiting in differential scanning calorimetry an onset temperature of substantially 207° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 50 .
  • One embodiment of the present disclosure provides a crystalline Form XVI of AP1189 oxalate exhibiting a differential scanning calorimetry thermogram according to FIG. 50 .
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 207 ⁇ 7° C., such as 207 ⁇ 6° C., such as 207 ⁇ 5° C., such as 207 ⁇ 4° C., such as 207 ⁇ 3° C., such as 207 ⁇ 2° C., such as 207 ⁇ 1° C.
  • One embodiment of the disclosure provides for a crystalline Form XVII of AP1189 oxalate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 51 .
  • One embodiment of the present disclosure provides a crystalline Form XVII of AP1189 oxalate exhibiting a differential scanning calorimetry thermogram according to FIG. 51 .
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting in differential scanning calorimetry an onset temperature between 198 and 212° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting in differential scanning calorimetry an onset temperature of substantially 205° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 52 .
  • One embodiment of the present disclosure provides a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 52 .
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 205 ⁇ 7° C., such as 205 ⁇ 6° C., such as 205 ⁇ 5° C., such as 205 ⁇ 4° C., such as 205 ⁇ 3° C., such as 205 ⁇ 2° C., such as 205 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting in differential scanning calorimetry an onset temperature between 74 and 88° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XIX of AP1189 oxoglutarate exhibiting in differential scanning calorimetry an onset temperature of substantially 81° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 53 .
  • One embodiment of the present disclosure provides a crystalline Form XIX of AP1189 oxoglutarate exhibiting a differential scanning calorimetry thermogram according to FIG. 53 .
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 81 ⁇ 7° C., such as 81 ⁇ 6° C., such as 81 ⁇ 5° C., such as 81 ⁇ 4° C., such as 81 ⁇ 3° C., such as 81 ⁇ 2° C., such as 81 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting in differential scanning calorimetry an onset temperature between 103 and 117° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XX of AP1189 DL-mandelic acid exhibiting in differential scanning calorimetry an onset temperature of substantially 110° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 54 .
  • One embodiment of the present disclosure provides a crystalline Form XX of AP1189 DL-mandelic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 54 .
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 110 ⁇ 7° C., such as 110 ⁇ 6° C., such as 110 ⁇ 5° C., such as 110 ⁇ 4° C., such as 1103° C., such as 1102° C., such as 110 ⁇ 1° C.
  • One embodiment of the disclosure provides for a crystalline Form XXI of AP1189 mandelic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 55 .
  • One embodiment of the present disclosure provides a crystalline Form XXI of AP1189 mandelic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 55 .
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting in differential scanning calorimetry an onset temperature between 132 and 146° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXII of AP1189 hippuric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 139° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 56 .
  • One embodiment of the present disclosure provides a crystalline Form XXII of AP1189 hippuric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 56 .
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 139 ⁇ 7° C., such as 139 ⁇ 6° C., such as 139 ⁇ 5° C., such as 139 ⁇ 4° C., such as 1393° C., such as 1392° C., such as 139 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting in differential scanning calorimetry an onset temperature between 162 and 176° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XIII of AP1189 formate exhibiting in differential scanning calorimetry an onset temperature of substantially 169° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 84 .
  • One embodiment of the present disclosure provides a crystalline Form XXIII of AP1189 formate exhibiting a differential scanning calorimetry thermogram according to FIG. 84 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate exhibiting in differential scanning calorimetry an onset temperature falling within the interval 169 ⁇ 7° C., such as 169 ⁇ 6° C., such as 169 ⁇ 5° C., such as 1694° C., such as 1693° C., such as 169 ⁇ 2° C., such as 169 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature between 182 and 196° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature of substantially 189° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 85 .
  • One embodiment of the present disclosure provides a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 85 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 189 ⁇ 7° C., such as 189 ⁇ 6° C., such as 189 ⁇ 5° C., such as 189 ⁇ 4° C., such as 189 ⁇ 3° C., such as 189 ⁇ 2° C., such as 189 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature between 191 and 205° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature of substantially 198° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 86 .
  • One embodiment of the present disclosure provides a crystalline Form XXV of AP1189 DL-lactic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 86 .
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 198 ⁇ 7° C., such as 198 ⁇ 6° C., such as 198 ⁇ 5° C., such as 198 ⁇ 4° C., such as 198 ⁇ 3° C., such as 198 ⁇ 2° C., such as 198 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature between 102 and 116° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 109° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 87 .
  • One embodiment of the present disclosure provides a crystalline Form XXVI of AP1189 glutaric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 87 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 109 ⁇ 7° C., such as 109 ⁇ 6° C., such as 109 ⁇ 5° C., such as 109 ⁇ 4° C., such as 109 ⁇ 3° C., such as 109 ⁇ 2° C., such as 109 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature between 153 and 167° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 160° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 87 .
  • One embodiment of the present disclosure provides a crystalline Form XXVI of AP1189 glutaric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 87 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 160 ⁇ 7° C., such as 160 ⁇ 6° C., such as 160 ⁇ 5° C., such as 160 ⁇ 4° C., such as 160 ⁇ 3° C., such as 160 ⁇ 2° C., such as 160 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature between 156 and 170° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXVII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 163° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 88 .
  • One embodiment of the present disclosure provides a crystalline Form XXVII of AP1189 glutaric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 88 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 163 ⁇ 7° C., such as 163 ⁇ 6° C., such as 163 ⁇ 5° C., such as 163 ⁇ 4° C., such as 163 ⁇ 3° C., such as 163 ⁇ 2° C., such as 163 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature between 138 and 152° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 145° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 89 .
  • One embodiment of the present disclosure provides a crystalline Form XXVIII of AP1189 glutaric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 89 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 145 ⁇ 7° C., such as 145 ⁇ 6° C., such as 145 ⁇ 5° C., such as 145 ⁇ 4° C., such as 145 ⁇ 3° C., such as 145 ⁇ 2° C., such as 145 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature between 153 and 167° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature of substantially 160° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 89 .
  • One embodiment of the present disclosure provides a crystalline Form XXVIII of AP1189 glutaric acid exhibiting a differential scanning calorimetry thermogram according to FIG. 89 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVIII of AP1189 glutaric acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 160 ⁇ 7° C., such as 160 ⁇ 6° C., such as 160 ⁇ 5° C., such as 160 ⁇ 4° C., such as 160 ⁇ 3° C., such as 160 ⁇ 2° C., such as 160 ⁇ 1° C.
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting in differential scanning calorimetry an onset temperature between 176 and 190° C.
  • One specific embodiment of the present disclosure provides a crystalline Form XXIX of AP1189 adipic acid exhibiting in differential scanning calorimetry an onset temperature of substantially 183° C.
  • the onset temperature is assessed using a heating rate of 10° C./min.
  • One embodiment of the disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting in differential scanning calorimetry an onset temperature as shown in the examples herein, specifically example 4, and/or in the figures herein, specifically FIG. 90 .
  • One embodiment of the present disclosure provides a crystalline Form XXIX of AP1189 adipic acid exhibiting a differential scanning calorimetry thermogram according to FIG. 90 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIX of AP1189 adipic acid exhibiting in differential scanning calorimetry an onset temperature falling within the interval 183 ⁇ 7° C., such as 183 ⁇ 6° C., such as 183 ⁇ 5° C., such as 183 ⁇ 4° C., such as 183 ⁇ 3° C., such as 183 ⁇ 2° C., such as 183 ⁇ 1° C.
  • FT-IR spectra may be obtained as outlined in Example 13. FT-IR are reported in peaks corresponding to specific wavenumbers given in cm ⁇ 1 . While the peaks are given herein with some degree of certainty, it is to be construed that the accuracy of an FT-IR measurement is typically ⁇ 1, ⁇ 2, or ⁇ 3 cm ⁇ 1 . Accordingly, any peak reported herein is to be interpreted as having an accuracy of ⁇ 1, 2, or ⁇ 3 cm ⁇ 1 .
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate having an FT-IR as shown in FIG. 57 .
  • One embodiment of the present disclosure provides for a crystalline Form III of AP1189 napadisylate having in an FT-IR spectrum peaks as shown in Table 45.
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate having an FT-IR as shown in FIG. 58 .
  • One embodiment of the present disclosure provides for a crystalline Form IV of AP1189 napadisylate having in an FT-IR spectrum peaks as shown in Table 46.
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate having an FT-IR as shown in FIG. 59 .
  • One embodiment of the present disclosure provides for a crystalline Form V of AP1189 esylate having in an FT-IR spectrum peaks as shown in Table 47.
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate having an FT-IR as shown in FIG. 60 .
  • One embodiment of the present disclosure provides for a crystalline Form VII of AP1189 edisylate having in an FT-IR spectrum peaks as shown in Table 48.
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate having an FT-IR as shown in FIG. 61 .
  • One embodiment of the present disclosure provides for a crystalline Form VIII of AP1189 edisylate having in an FT-IR spectrum peaks as shown in Table 49.
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate having an FT-IR as shown in FIG. 62 .
  • One embodiment of the present disclosure provides for a crystalline Form IX of AP1189 edisylate having in an FT-IR spectrum peaks as shown in Table 50.
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate having an FT-IR as shown in FIG. 63 .
  • One embodiment of the present disclosure provides for a crystalline Form X of AP1189 nitrate having in an FT-IR spectrum peaks as shown in Table 51.
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate having an FT-IR as shown in FIG. 64 .
  • One embodiment of the present disclosure provides for a crystalline Form XI of AP1189 cyclamate having in an FT-IR spectrum peaks as shown in Table 52.
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate having an FT-IR as shown in FIG. 65 .
  • One embodiment of the present disclosure provides for a crystalline Form XII of AP1189 cyclamate having in an FT-IR spectrum peaks as shown in Table 53.
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate having an FT-IR as shown in FIG. 66 .
  • One embodiment of the present disclosure provides for a crystalline Form XIII of AP1189 cyclamate having in an FT-IR spectrum peaks as shown in Table 54.
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate having an FT-IR as shown in FIG. 67 .
  • One embodiment of the present disclosure provides for a crystalline Form XIV of AP1189 besylate having in an FT-IR spectrum peaks as shown in Table 55.
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate having an FT-IR as shown in FIG. 68 .
  • One embodiment of the present disclosure provides for a crystalline Form XV of AP1189 oxalate having in an FT-IR spectrum peaks as shown in Table 56.
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate having an FT-IR as shown in FIG. 69 .
  • One embodiment of the present disclosure provides for a crystalline Form XVI of AP1189 oxalate having in an FT-IR spectrum peaks as shown in Table 57.
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate having an FT-IR as shown in FIG. 70 .
  • One embodiment of the present disclosure provides for a crystalline Form XVII of AP1189 oxalate having in an FT-IR spectrum peaks as shown in Table 58.
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid having an FT-IR as shown in FIG. 71 .
  • One embodiment of the present disclosure provides for a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid having in an FT-IR spectrum peaks as shown in Table 59.
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate having an FT-IR as shown in FIG. 72 .
  • One embodiment of the present disclosure provides for a crystalline Form XIX of AP1189 oxoglutarate having in an FT-IR spectrum peaks as shown in Table 60.
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid having an FT-IR as shown in FIG. 73 .
  • One embodiment of the present disclosure provides for a crystalline Form XX of AP1189 DL-mandelic acid having in an FT-IR spectrum peaks as shown in Table 61.
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid having an FT-IR as shown in FIG. 74 .
  • One embodiment of the present disclosure provides for a crystalline Form XXI of AP1189 DL-mandelic acid having in an FT-IR spectrum peaks as shown in Table 62.
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid having an FT-IR as shown in FIG. 75 .
  • One embodiment of the present disclosure provides for a crystalline Form XXII of AP1189 hippuric acid having in an FT-IR spectrum peaks as shown in Table 63.
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate having an FT-IR as shown in FIG. 76 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIII of AP1189 formate having in an FT-IR spectrum peaks as shown in Table 64.
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid having an FT-IR as shown in FIG. 77 .
  • One embodiment of the present disclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acid having in an FT-IR spectrum peaks as shown in Table 65.
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid having an FT-IR as shown in FIG. 78 .
  • One embodiment of the present disclosure provides for a crystalline Form XXV of AP1189 DL-lactic acid having in an FT-IR spectrum peaks as shown in Table 66.
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid having an FT-IR as shown in FIG. 79 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVI of AP1189 glutaric acid having in an FT-IR spectrum peaks as shown in Table 67.
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid having an FT-IR as shown in FIG. 80 .
  • One embodiment of the present disclosure provides for a crystalline Form XXVII of AP1189 glutaric acid having in an FT-IR spectrum peaks as shown in Table 68.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetic acid having an IR spectrum as shown in FIG. 92 .
  • solubility in aqueous solution is preferably meant.
  • solubility is in aqueous medium.
  • the crystalline Form A of AP1189 acetate was found to have a high solubility at pH 1.2.
  • crystalline Form B of AP1189 succinate was found to have a higher solubility at pH 1.2-1.3. It is an object of the present disclosure to provide salts of AP1189 having a high solubility at low pH, as this improves in vivo uptake of AP1189 after administration to a subject, such as oral administration to a subject.
  • One embodiment of the present disclosure provides for a salt of AP1189 having a solubility at pH 1.2 of at least 10 mM, such as 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.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate having a solubility at pH 1.2 of at least 100 mM, such as at least 110 mM, such as at least 120 mM.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate having a solubility at pH 1.2 of at least 20 mM, such as at least 25 mM, such as at least 30 mM, such as at least 35 mM.
  • the solubility of a compound may be assessed by adding a surplus of the compound to a volume of solvent such that some of the compound is not dissolved, then isolating the non-dissolved compound and measuring the amount.
  • the solubility of a compound may alternatively be assessed by adding a surplus of the compound to a volume of solvent such that some of the compound is not dissolved, and then measure the amount of compound in solution. Measuring the amount of compound in solution may be done using any suitable method, such as HPLC, titration, or spectrometry.
  • Salts of AP1189 may be prepared as disclosed herein.
  • One embodiment of the present disclosure provides for a method of producing AP1189 acetate of crystalline Form A, said method comprising:
  • mixture can mean a solution or a slurry of one or more solids in a solvent or mixture of solvents.
  • the mixture is a solution, where the solute or solutes are substantially fully dissolved.
  • the mixture is a slurry, wherein one or more solutes are only partly dissolved, and the remaining part or parts of the solute or solutes are not dissolved.
  • One embodiment of the present disclosure provides for a method for producing AP1189 acetate of crystalline Form A, said method comprising:
  • the acetate salt is ammonium acetate or a metal acetate salt such as sodium acetate, lithium acetate, magnesium acetate, potassium acetate, or calcium acetate.
  • the method further comprises adding an acid in step i, such as an organic acid or a mineral acid.
  • One embodiment of the disclosure provides for a method for producing AP1189 acetate of crystalline Form A, said method comprising:
  • such method is effective in converting AP1189 acetate not of crystalline Form A to AP1189 acetate of crystalline Form A.
  • composition can mean a solution or a slurry of one solid in a solvent or mixture of solvents.
  • the composition is a solution, where the solute is substantially fully dissolved.
  • the composition is a slurry, wherein the solute is only partly dissolved, and the remaining part of the solute is not dissolved.
  • the composition may further comprise one or more other agents or reagents which may be dissolved or may be only partly dissolved.
  • Such other agents includes, but are not limited to, surfactants, detergents, acids, bases, sugars, salts, biomolecules, bioactive agents, and other excipients such as pharmaceutical excipients.
  • This present disclosure also relates to non-solid compositions, e.g. liquid compositions, gel compositions, pastes, creams, or ointments prepared from the crystalline forms disclosed herein.
  • a liquid composition prepared from a crystalline form disclosed herein and a solvent In a specific embodiment, the solvent is aqueous.
  • the present disclosure provides for a method of preparing a liquid composition, a gel composition, a paste, a cream, or an ointment, said method comprising mixing a crystalline form disclosed herein and one or more additional agents.
  • a method of preparing a liquid composition said method comprising mixing a crystalline form disclosed herein and a solvent.
  • the solvent is aqueous.
  • One embodiment of the disclosure provides for a method for producing N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate of crystalline Form A, said method comprising:
  • any one of the above agents of step i may be generated from a precursor in situ.
  • One embodiment of the present disclosure provides for a method for producing N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium acetate of crystalline Form A, said method comprising:
  • One embodiment of the present disclosure provides for a method of producing AP1189 succinate of crystalline Form B, said method comprising:
  • One embodiment of the present disclosure provides for a method of producing AP1189 succinate of crystalline Form B, said method comprising:
  • One embodiment of the present disclosure provides for a method for producing the N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate of crystalline Form B, said method comprising:
  • any one of the above agents of step i may be generated from a precursor in situ.
  • One embodiment of the present disclosure provides for a method for producing the N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium succinate of crystalline Form B, said method comprising:
  • the solvent is a protic or a polar aprotic solvent.
  • the solvent is selected from the group consisting of 1,4-dioxane, methanol, ethanol, 1-propanol, 2-propanol, acetone, acetonitrile, anisole, isopropyl acetate, methylethyl ketone, water, and ethyl acetate.
  • the mixture or the composition is heated at least once before the isolating step. In one embodiment, the mixture or the composition is heated and cooled in cycles before the isolation step. In one embodiment, the mixture or the composition is heated and cooled in cycles for up to 72 hours before the isolating step. In one embodiment the mixture or the composition is heated and cooled in cycles for 15 min to 72 hours before the isolating step. In one embodiment, one cycle comprises heating the mixture or the composition to at least a first threshold temperature, maintaining the temperature above said first threshold temperature for a first duration, then cooling the mixture or the composition to below a second threshold temperature and maintaining the temperature below said second threshold temperature for a second duration. In one embodiment of the present disclosure, the cycle is carried out 1 to 200 times.
  • 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.
  • the second threshold temperature is 30° C., such as 25° C., such as 20° C., such as 15° C., such as 10° C., such as 7° C., such as 5° C.
  • the first and/or the second duration is 1 to 2 min, such as 2 to 5 min, such as 5 to 10 min, such as 10 to 20 min, such as 20 to 30 min, such as 30 to 40 min, such as 40 to 50 min, such as 50 to 60 min, such as 1 hour to 1.5 hours, such as 1.5 to 2 hours, such as 2 to 3 hours, such as 3 to 4 hours, such as 4 to 5 hours, such as 5 to 6 hours, such as 6 to 7 hours, such as 7 to 8 hours.
  • the first and the second durations are the same. In one embodiment, the first and the second durations 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.
  • heating is to about 40° C.
  • cooling is to about 20° C.
  • the method further comprises a step of adding an anti-solvent to the mixture or the composition before the isolation step.
  • the anti-solvent is a non-polar aprotic solvent.
  • 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.
  • the anti-solvent is water.
  • Isolation of crystals may be carried out using an appropriate means.
  • the isolation is carried out using filtration, centrifugation, and/or evaporation of the solvent or solvents.
  • a slow evaporation method is utilised.
  • a fast evaporation method is utilised.
  • the evaporation is carried out using spray drying.
  • the evaporation is carried out using fluid bed drying, freeze drying, vacuum drying, tumble drying, rotary evaporation, and/or thin-film evaporation.
  • the drying is carried out using a conductive (contact) dryer, including tray dryers, rotary cone dryers, tumble dryers, and paddle dryers.
  • the drying is carried out using a carrier gas.
  • one or more pKa values, such as at least one pKa, of the corresponding acid to the counter ion of the AP1189 salt is about equal to or lower than the pKa value of succinic acid and/or acetic acid.
  • the corresponding acid to the counter ion of the AP1189 fumarate 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.
  • the pKa value of the corresponding acid to the counter ion of the AP1189 salt is about equal to or lower than 4.756. In another embodiment, the pKa value of the corresponding acid to the counter ion of the AP1189 salt is about equal to or lower than 4.2 and/or 5.6.
  • One embodiment of the present disclosure provides for a crystalline Form A of AP1189 acetate produced by the method as disclosed herein.
  • One embodiment of the present disclosure provides for a crystalline Form B of AP1189 succinate produced by the method as disclosed herein.
  • One embodiment of the present disclosure provides for a method of producing crystalline Form A of AP1189 acetate as disclosed herein, wherein the method further comprises adding a seed crystal of crystalline Form A of AP1189 acetate before the isolation step.
  • One embodiment of the present disclosure provides for a method of producing crystalline Form B of AP1189 succinate as disclosed herein, wherein the method further comprises adding a seed crystal of crystalline Form B of AP1189 succinate before the isolation step.
  • One embodiment of the disclosure provides for a pharmaceutical composition
  • a pharmaceutical composition comprising the crystalline Form A of AP1189 acetate as disclosed herein and a pharmaceutically acceptable excipient.
  • One embodiment of the disclosure provides for a pharmaceutical composition
  • a pharmaceutical composition comprising the crystalline Form B of AP1189 succinate as disclosed herein and a pharmaceutically acceptable excipient.
  • an oral formulation, a pharmaceutical composition, or unit dosage form comprising the crystalline Form A of AP1189 acetate as disclosed herein or the crystalline Form B of AP1189 succinate as disclosed herein.
  • compositions as disclosed herein, wherein the pharmaceutical composition is formulated for oral administration.
  • Such composition may be in the form of a tablet or a capsule.
  • One embodiment of the disclosure provides for a method of preparing a pharmaceutical composition comprising mixing the crystalline Form A of AP1189 acetate with a pharmaceutically acceptable excipient.
  • One embodiment of the disclosure provides for a method of preparing a pharmaceutical composition comprising mixing the crystalline Form B of AP1189 succinate with a pharmaceutically acceptable excipient.
  • One embodiment of the disclosure provides for the crystalline Form A of AP1189 acetate, the crystalline Form B of AP1189 succinate, or the pharmaceutical composition as disclosed herein for use in medicine.
  • One embodiment of the present disclosure provides for the crystalline Form A of AP1189 acetate, the crystalline Form B of AP1189 succinate, or the pharmaceutical composition as disclosed herein, for use in the treatment of a kidney disease such as proteinuria, a cardiovascular disease, an arthritic disease, or a viral infection.
  • One embodiment of the present disclosure provides for a method of treating a disease or disorder in a subject in need thereof, said method comprising administering crystalline Form A of AP1189 acetate, crystalline Form B of AP1189 succinate, or the pharmaceutical composition as disclosed herein, to a subject in need thereof.
  • the disease or disorder is selected from the list consisting of a kidney disease such as proteinuria, a cardiovascular disease, an arthritic disease, or a viral infection.
  • One embodiment of the present disclosure provides for a use of the crystalline Form A of AP1189 acetate or the crystalline Form B of AP1189 succinate, or the pharmaceutical composition as disclosed herein for the manufacture of a medicament for treatment of a disease or disorder.
  • a pharmaceutical formulation such as an oral formulation, comprising the crystalline Form A of AP1189 acetate as disclosed herein or the crystalline Form B of AP1189 succinate as disclosed herein, for use in the treatment of a disease or disorder.
  • the disease or disorder is selected from the group consisting of a kidney disease, an arthritic disease, a viral disease or disorder, and a cardiovascular disease and/or atherosclerosis.
  • 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 kidney disease.
  • an oral formulation such as a solid oral formulation, comprising the crystalline form A of AP1189 acetate or the crystalline Form B of AP1189 succinate, and at least one pharmaceutically acceptable excipient, as disclosed herein, for use in treating or preventing a kidney disease.
  • kidney disease present with proteinuria. In some embodiments said kidney disease is a proteinuric kidney disease.
  • said kidney disease is nephrotic syndrome (glomerulonephrosis).
  • said kidney disease is primary nephrotic syndrome (primary glomerulonephrosis).
  • said primary nephrotic syndrome is membranous glomerulonephritis (MGN) (or membranous nephropathy (MN)).
  • MGN membranous glomerulonephritis
  • MN membranous nephropathy
  • said primary nephrotic syndrome is focal segmental glomerulosclerosis (FSGS).
  • FSGS focal segmental glomerulosclerosis
  • said primary nephrotic syndrome is membranoproliferative glomerulonephritis (MPGN) (mesangiocapillary glomerulonephritis).
  • MPGN membranoproliferative glomerulonephritis
  • said membranoproliferative glomerulonephritis is selected from Type 1 MPGN and Type 2 MPGN.
  • said primary nephrotic syndrome is rapidly progressive glomerulonephritis (RPGN) (crescentic GN).
  • said primary nephrotic syndrome is minimal change disease (MCD).
  • said kidney disease is secondary nephrotic syndrome (secondary glomerulonephrosis).
  • said secondary nephrotic syndrome is caused by an underlying autoimmune disease, an underlying cancer disease, an underlying genetic disorder, or by an underlying disease selected from the group consisting of: Systemic lupus erythematosus (SLE), Diabetic nephropathy, Sarcoidosis, Sjögren's syndrome, Amyloidosis, Multiple myeloma, Vasculitis, Cancer and Genetic disorders (such as congenital nephrotic syndrome).
  • SLE Systemic lupus erythematosus
  • said secondary nephrotic syndrome is caused by Diabetic nephropathy, by an infection, such as a urinary tract infection, such as an infection selected from the group consisting of HIV, syphilis, hepatitis such as hepatitis A, B and C, post-streptococcal infection, urinary schistosomiasis and Ebola.
  • an infection such as a urinary tract infection, such as an infection selected from the group consisting of HIV, syphilis, hepatitis such as hepatitis A, B and C, post-streptococcal infection, urinary schistosomiasis and Ebola.
  • said secondary nephrotic syndrome is drug-induced.
  • said kidney disease is an inflammatory kidney disease.
  • said kidney disease is glomerulonephritis (GN).
  • said glomerulonephritis is selected from the group consisting of IgA nephropathy (Berger's disease), IgM nephropathy, Post-infectious glomerulonephritis and Thin basement membrane disease.
  • kidney disease is idiopathic membranous nephropathy (iMN).
  • iMN idiopathic membranous nephropathy
  • an oral formulation, a pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing idiopathic membranous nephropathy (iMN).
  • iMN idiopathic membranous nephropathy
  • 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.
  • an oral formulation such as a solid oral formulation, comprising the crystalline Form A of AP1189 acetate or crystalline Form B of AP1189 succinate, and at least one pharmaceutically acceptable excipient, as disclosed herein, for use in treating or preventing an arthritic disease.
  • the arthritic disease is an auto-immune disease and/or an inflammatory disease that presents with joint inflammation.
  • the arthritic disease is selected from the group consisting of inflammatory arthritis, degenerative arthritis, metabolic arthritis, reactive arthritis and infectious arthritis.
  • the arthritic disease is inflammatory arthritis.
  • the inflammatory arthritis is selected from the group consisting of Rheumatoid Arthritis (RA), Psoriatic Arthritis, and Ankylosing Spondylitis.
  • RA Rheumatoid Arthritis
  • Psoriatic Arthritis Psoriatic Arthritis
  • Ankylosing Spondylitis Rheumatoid Arthritis
  • the inflammatory arthritis is Rheumatoid Arthritis (RA).
  • RA Rheumatoid Arthritis
  • the rheumatoid arthritis is severe active RA (CDAI>22). In one embodiment, the rheumatoid arthritis is RA with a CDAI>22.
  • the rheumatoid arthritis is RA with a DAS28 score of above 5.1.
  • the rheumatoid arthritis is juvenile rheumatoid arthritis (JRA).
  • the degenerative arthritis is osteoarthritis.
  • the metabolic arthritis is gouty arthritis.
  • the reactive and/or infectious arthritis is arthritis associated with infection with one or more of Hepatitis C, Chlamydia , gonorrhoea, salmonella or shigella.
  • the arthritic disease is arthritis as part of a systemic inflammatory disease.
  • the arthritis as part of a systemic inflammatory disease, such as an inflammatory disease selected from the group consisting of systemic lupus erythematosus, mixed connective tissue disease, Still's disease, and Polymyalgia Rheumatica.
  • a systemic inflammatory disease such as an inflammatory disease selected from the group consisting of systemic lupus erythematosus, mixed connective tissue disease, Still's disease, and Polymyalgia Rheumatica.
  • an oral formulation, a pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing rheumatoid arthritis.
  • MTX metalhotrexate
  • an oral formulation, a pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing rheumatoid arthritis in patients with an inappropriate response to MTX (such as patients with a reduced response to MTX treatment, such as an MTX non-responder).
  • MTX metalhotrexate
  • 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.
  • an oral formulation such as a solid oral formulation, comprising a pharmaceutically acceptable salt of AP1189, such as AP1189 acetate or AP1189 succinate, and at least one pharmaceutically acceptable excipient, as disclosed herein, for use in treating or preventing a viral disease or disorder.
  • a pharmaceutically acceptable salt of AP1189 such as AP1189 acetate or AP1189 succinate
  • at least one pharmaceutically acceptable excipient as disclosed herein
  • said viral disease or disorder is a symptomatic viral disease or disorder.
  • said viral disease or disorder is a symptomatic viral disease or disorder with inflammation, such as hyperinflammation.
  • said viral disease or disorder is a symptomatic viral disease or disorder with inflammation, such as hyperinflammation, in one or more organs.
  • Inflammation in one or more organs may also be referred to as local inflammation.
  • said one or more organs are selected from the group consisting of lungs, the respiratory tract, kidney, liver, pancreas, spleen, exocrine glands, endocrine glands, lymph nodes, brain, heart, muscles, bone marrow, skin, skeleton, bladder, reproduction organs including the phallopian tubes, eye, ear, vascular system, the gastrointestinal tract including small intestines, colon, rectum, canalis analis and the prostate gland.
  • said viral disease or disorder is inflammatory viral diseases or disorders.
  • said viral disease or disorder is a viral respiratory infection, such as a viral lower respiratory infection.
  • said viral disease or disorder is viral respiratory diseases or disorders.
  • said viral disease or disorder is viral diseases or disorders of the lung.
  • said viral disease or disorder is viral diseases or disorders with inflammation in the respiratory system, such as in the lungs and/or respiratory tract.
  • said viral disease or disorder is viral diseases or disorders with one or more respiratory symptoms.
  • said one or more respiratory symptoms are selected from the group consisting of cough, dry cough, dyspnea, impaired oxygenation, respiratory illness, respiratory dysfunction, respiratory failure, respiratory syndrome and acute respiratory disease (ARD).
  • said viral disease or disorder is severe disease. Severe disease present with dyspnoea, increased respiratory frequency, reduced blood oxygen saturation and/or lung infiltrates.
  • said viral disease or disorder is critical disease.
  • Critical disease present with respiratory failure, septic shock, and/or multiple organ dysfunction (MOD) or multiple organ failure (MOF).
  • said viral disease or disorder is viral pneumonia.
  • said viral disease or disorder is viral bronchiolitis.
  • said viral disease or disorder is viral diseases or disorders with respiratory failure.
  • said viral disease or disorder is acute respiratory distress syndrome (ARDS).
  • ARDS acute respiratory distress syndrome
  • said viral disease or disorder is viral acute respiratory distress syndrome (ARDS).
  • ARDS viral acute respiratory distress syndrome
  • said viral disease or disorder is symptomatic COVID-19 with acute respiratory distress syndrome (ARDS).
  • ARDS acute respiratory distress syndrome
  • an oral formulation, a pharmaceutical composition, or unit dosage form according to the present disclosure for use in treating or preventing ARDS, such as viral ARDS.
  • said viral disease or disorder is viral diseases and disorders with systemic inflammatory distress syndrome (SIDS) and/or sepsis.
  • SIDS systemic inflammatory distress syndrome
  • said viral disease or disorder is viral diseases and disorders with pulmonary insufficiency.
  • said viral disease or disorder is viral diseases or disorders with cytokine release syndrome (CRS) and/or a cytokine storm (hypercytokinemia).
  • CRS cytokine release syndrome
  • hypercytokinemia hypercytokinemia
  • said 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 the COVID-19 virus; SARS-CoV, MERS-CoV, the dengue virus and influenza virus (including Type A, Type B and Type C).
  • SARS-CoV-2 Severe Acute Respiratory Syndrome CoronaVirus 2
  • MERS-CoV the dengue virus and influenza virus
  • Type A, Type B and Type C a viral infection selected from the group consisting of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), often referred to as the COVID-19 virus; SARS-CoV, MERS-CoV, the dengue virus and influenza virus (including Type A, Type B and Type C).
  • 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 cardiovascular disease and/or atherosclerosis.
  • an oral formulation such as a solid oral formulation, comprising the crystalline Form A of AP1189 acetate as disclosed herein or the crystalline Form B of AP1189 succinate as disclosed herein, and at least one pharmaceutically acceptable excipient, as disclosed herein, for use in treating or preventing a cardiovascular disease and/or atherosclerosis.
  • said cardiovascular disease is selected from the group consisting of coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack); stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, vascular disease, thromboembolic disease, and venous thrombosis.
  • CAD coronary artery diseases
  • said cardiovascular disease is atherosclerotic cardiovascular disease.
  • said atherosclerotic cardiovascular disease is selected from the group consisting of coronary artery disease, stroke (cerebrovascular disease), and peripheral artery disease.
  • said cardiovascular disease is vascular inflammation.
  • 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 disorder.
  • an oral formulation such as a solid oral formulation, comprising the crystalline Form A of AP1189 acetate as disclosed herein or the crystalline Form B of AP1189 succinate, and at least one pharmaceutically acceptable excipient, as disclosed herein, for use in treating or preventing a systemic inflammatory disorder.
  • Systemic disorders with possible involvement of the nervous system include a variety of diseases with presumed inflammatory and autoimmune pathomechanisms, among them Behçet disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögren syndrome.
  • This disease group encompasses systemic inflammatory disorders with a genetically defined dysregulation of the innate immune system as well as systemic autoimmune disorders characterized by alterations of the adaptive immunity such as autoantibodies and autoreactive T cells.
  • said systemic inflammatory disorder is an autoimmune disorder.
  • said systemic inflammatory disorder is selected from the group consisting of Behçet disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, Sjögren syndrome, myositis including dermamyositis and polymyositis, vasculitis, giant cell arteritis, ankylosing spondylitis, polymyalgia rheumatic and psoriatic arthritis.
  • An acid is added as a slurry or solution in a protic or polar aprotic solvent to a heated slurry or solution of 3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal and aminoguanidine or a salt thereof in a protic or polar aprotic solvent.
  • the resulting mixture is heated and stirred, preferably until completion of the reaction, before 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 solvents, including spray drying.
  • An acid is added (such as an excess of said acid) as a slurry or solution in a protic or polar aprotic solvent to a slurry of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidine in a protic or polar aprotic solvent.
  • the resulting mixture is heated and cooled in cycles between 15 min and 72 hours, before 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 solvents, including spray drying.
  • This method is feasible if the corresponding acid to the counterion is stronger in the salt formed.
  • An excess of an acid is added as a slurry or solution in a protic or polar aprotic solvent to a slurry of N- ⁇ 3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene ⁇ -aminoguanidinium salt in a protic or polar aprotic solvent.
  • the resulting mixture is heated and cooled in cycles between 15 min and 72 hours, before 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 solvents, including spray drying.
  • 2-propanol:water 90:10 v/v was added to AP1189 acetate to prepare a slurry.
  • 2-propanol:water 90:10 v/v was added to 1.1 equivalents of succinic acid.
  • the counterion slurry was added to the acetate salt slurry.
  • Temperature cycling was carried out between ambient and 40° C. for ca. 18 h with 4 hour hold periods at ambient temperature and 4 hour hold periods at 40° C. The entire slurry was then isolated by Buchner filtration and washed with deionised water. The solids were dried under vacuum at ambient.
  • a polymorphism assessment was carried out in order to identify alternate polymorphs of AP1189 acetate: AP1189 acetate was dissolved in 1,4-dioxane-water and lyophilized to obtain an amorphous solid. Aliquots were suspended in the specific solvents and heated in temperature cycles between ambient and 40° C. for 3 days, before being isolated by filtration.
  • Acetate Pattern 1 was obtained from 8 solvent systems.
  • a mixture of Pattern 1 and 2 was obtained from 8 solvent systems.
  • Pattern 3 was obtained from THF. Extended temperature cycling for a further 3 days for the acetate Pattern 1 and 2 mixture from ethyl acetate resulted in conversion to acetate Pattern 1.
  • XRPD analysis was carried out on a PANalytical X'pert pro with PIXcel detector (128 channels), scanning the samples between 3 and 35° 2 ⁇ .
  • the material was gently ground (where required) to release any agglomerates and loaded onto a multi-well plate with Kapton or Mylar polymer film to support the sample.
  • the XRPD diffractogram for AP1189 acetate salt Pattern 1 crystallised from acetonitrile is shown in FIG. 1 .
  • the corresponding XRPD diffractogram peak list for acetate Pattern 1 is shown in Table 3.
  • Indexed unit cell data a [ ⁇ ] 7.8; b [ ⁇ ] 15.1; c [ ⁇ ] 20.7; alpha [°] 73.6; beta [°] 80.5; gamma [°] 86.5; volume [ ⁇ 3 ] 2311.8.
  • the XRPD diffractogram for AP1189 acetate salt Pattern 1 and 2 crystallised from ethyl acetate is shown in FIG. 2 .
  • the corresponding XRPD diffractogram peak list for acetate salt Pattern 1 and 2 is shown in Table 4.
  • the XRPD diffractogram for AP1189 acetate salt Pattern 3 crystallised from THF is shown in FIG. 3 .
  • the corresponding XRPD diffractogram peak list for acetate salt Pattern 3 is shown in Table 5.
  • the XRPD diffractogram for AP1189 tosylate salt Pattern 1 crystallised from methanol is shown in FIG. 4 .
  • the corresponding XRPD diffractogram peak list for tosylate salt Pattern 1 is shown in Table 6.
  • the XRPD diffractogram for AP1189 fumarate salt Pattern 1 crystallised from isopropylalcohol:water 90:10 v/v is shown in FIG. 5 .
  • the corresponding XRPD diffractogram peak list for fumarate salt Pattern 1 from isopropylalcohol:water 90:10 v/v is shown in Table 7.
  • the XRPD diffractogram for AP1189 succinate salt Pattern 1 crystallised from isopropanol:water 90:10 v/v is shown in FIG. 6 .
  • the corresponding XRPD diffractogram peak list for succinate salt Pattern 1 is shown in Table 8.
  • the corresponding XRPD diffractogram peak list for napadisylate salt Pattern 1 is shown in Table 9.
  • the XRPD diffractogram for AP1189 napadisylate salt Pattern 2 crystallised from THF is shown in FIG. 15 .
  • the corresponding XRPD diffractogram peak list for napadisylate salt Pattern 2 is shown in Table 10.
  • the XRPD diffractogram for AP1189 esylate salt Pattern 1 crystallised from methylethyl ketone is shown in FIG. 16 .
  • the corresponding XRPD diffractogram peak list for esylate salt Pattern 1 is shown in Table 11.
  • the corresponding XRPD diffractogram peak list for edisylate salt Pattern 1 is shown in Table 12.
  • the XRPD diffractogram for AP1189 edisylate salt Pattern 2 crystallised from methylethyl ketone is shown in FIG. 18 .
  • the corresponding XRPD diffractogram peak list for edisylate salt Pattern 2 is shown in Table 13.
  • the XRPD diffractogram for AP1189 edisylate salt Pattern 4 crystallised from THF is shown in FIG. 19 .
  • the corresponding XRPD diffractogram peak list for edisylate salt Pattern 4 is shown in Table 14.
  • the corresponding XRPD diffractogram peak list for edisylate salt Pattern 5 is shown in Table 15.
  • the XRPD diffractogram for AP1189 nitrate salt Pattern 1 crystallised from THF is shown in FIG. 21 .
  • the corresponding XRPD diffractogram peak list for nitrate salt Pattern 1 is shown in Table 16.
  • the XRPD diffractogram for AP1189 cyclamate salt Pattern 2 crystallised from THF is shown in FIG. 22 .
  • the corresponding XRPD diffractogram peak list for cyclamate salt Pattern 2 is shown in Table 17.
  • the XRPD diffractogram for AP1189 cyclamate salt Pattern 4 crystallised from acetone is shown in FIG. 23 .
  • the corresponding XRPD diffractogram peak list for cyclamate salt Pattern 4 is shown in Table 18.
  • the XRPD diffractogram for AP1189 cyclamate salt Pattern 5 crystallised from THF is shown in FIG. 24 .
  • the corresponding XRPD diffractogram peak list for cyclamate salt Pattern 5 is shown in Table 19.
  • the corresponding XRPD diffractogram peak list for besylate salt Pattern 1 is shown in Table 20.
  • the corresponding XRPD diffractogram peak list for oxalate salt Pattern 1 is shown in Table 21.
  • the XRPD diffractogram for AP189 oxalate salt Pattern 2 crystallised from acetone is shown in FIG. 27 .
  • the corresponding XRPD diffractogram peak list for oxalate salt Pattern 2 is shown in Table 22.
  • the XRPD diffractogram for AP1189 oxalate salt Pattern 4 crystallised from THF is shown in FIG. 28 .
  • the corresponding XRPD diffractogram peak list for oxalate salt Pattern 4 is shown in Table 23.
  • the corresponding XRPD diffractogram peak list for (+)-camphor-10-sulfonic acid salt Pattern 1 is shown in Table 24.
  • the XRPD diffractogram for AP1189 oxoglutarate salt Pattern 1 crystallised from acetone is shown in FIG. 30 .
  • the corresponding XRPD diffractogram peak list for oxoglutarate salt Pattern 1 is shown in Table 25.
  • the XRPD diffractogram for AP1189 DL-mandelic acid salt Pattern 2 crystallised from methylethyl ketone is shown in FIG. 31 .
  • the corresponding XRPD diffractogram peak list for DL-mandelic acid salt Pattern 2 is shown in Table 26.
  • the XRPD diffractogram for AP1189 DL-mandelic acid salt Pattern 3 crystallised from acetone is shown in FIG. 32 .
  • the corresponding XRPD diffractogram peak list for DL-mandelic acid salt Pattern 3 is shown in Table 27.
  • the XRPD diffractogram for AP1189 hippuric acid salt Pattern 1 crystallised from methylethyl ketone is shown in FIG. 33 .
  • the corresponding XRPD diffractogram peak list for hippuric acid salt Pattern 1 is shown in Table 28.
  • the XRPD diffractogram for AP1189 formate salt Pattern 1 crystallised from acetone is shown in FIG. 34 .
  • the corresponding XRPD diffractogram peak list for formate salt Pattern 1 is shown in Table 29.
  • the XRPD diffractogram for AP1189 DL-lactic acid salt Pattern 1 crystallised from acetone is shown in FIG. 35 .
  • the corresponding XRPD diffractogram peak list for L-lactic acid salt Pattern 1 is shown in Table 30.
  • the XRPD diffractogram for AP1189 DL-lactic acid salt Pattern 1 crystallised from 2-propanol:water 80:20% v/v is shown in FIG. 36 .
  • the corresponding XRPD diffractogram peak list for DL-lactic acid salt Pattern 1 is shown in Table 31.
  • the XRPD diffractogram for AP1189 glutaric acid salt Pattern 1 crystallised from acetone is shown in FIG. 37 .
  • the corresponding XRPD diffractogram peak list for glutaric acid salt Pattern 1 is shown in Table 32.
  • the XRPD diffractogram for AP1189 glutaric acid salt Pattern 2 crystallised from methylethyl ketone is shown in FIG. 38 .
  • the corresponding XRPD diffractogram peak list for glutaric acid salt Pattern 2 is shown in Table 33.
  • the XRPD diffractogram for AP1189 glutaric acid salt Pattern 4 crystallised from acetone is shown in FIG. 91
  • the corresponding XRPD diffractogram peak list for glutaric acid salt Pattern 4 is shown in Table 34.
  • the XRPD diffractogram for AP1189 adipic acid salt Pattern 1 crystallised from 2-Propanol:water 80:20% v/v is shown in FIG. 39 .
  • the corresponding XRPD diffractogram peak list for adipic acid salt Pattern 1 is shown in Table 35.
  • AP1189 napadisylate 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • AP1189 DL-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).
  • 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).
  • test compounds exhibited remarkably different solubilities, especially at low pH. Specifically, the acetate and succinate salts showed high solubility at pH 1.2, indicating the potential for using these compounds in applications where a high solubility at low pH is desirable.
  • the solids were analysed by XRPD to check the polymorphic form. The remainder of the solids were druid under vacuum at ambient for ca. 3 days. The dried solids were characterised. The concentrations of the recovered mother liquors and was were determined by HPLC.
  • AP1189 was added to 20 mL vials. The required volume of the appropriate solvent system was added to each vial, and the experiments were stirred at 65-69° C. The experiments were then cooled to 55° C., and seeded with AP1189 succinate. 2% seed load was used. The experiments were stirred at 55° C. for another 1 h to allow for equilibration. The experiments were then cooled to 5° C. at 0.1° C./min, and stirred at 5° C. After ca. 18 h of stirring at 5° C., 200 ⁇ L aliquot of each slurry was extracted and centrifuged using 0.2 ⁇ m nylon tubes.
  • the isolated solids were dried under vacuum at ambient and analysed by HPLC (purity). The concentration and purity of the mother liquors were also determined by HPLC. To the remainder of the experiments, anti-solvent addition was carried out at 5° C., to reach the target final ratio. Afterwards, stirring continued at 5° C. for another ca. 4 h. The experiments (slurries) were vacuum filtered and the cakes each washed with 0.9 mL of the respective organic solvent (pre-cooled at 5° C.). The solids were dried under vacuum at ambient for ca. 48 h. The dried solids were characterised. The mother liquors were subsampled and analysed by HPLC for concentration and solution purity determination. The rest of the mother liquors were left open in an oven, to allow the solvents to evaporate under vacuum, at ambient. After 3 days, the residual solids were analysed by XRPD and HPLC (purity).
  • AP1189 succinate exhibiting the crystal form of Pattern 1 was obtained using various crystallisation conditions. Isolated yield obtained was between 65 and 80%. Addition of water as anti-solvent improved the theoretical yield by 2 to 6% % w/w.
  • AP1189 succinate was added to temperature controlled reactor in an EasyMax 102 (100 mL vessel). 55.6 mL (11.1 vol.) of 1-propanol/water (50:50 v/v %) was added to the reactor, and the experiment was stirred at 70° C. Target concentration was 90 mg/mL. Stirring speed was 200 rpm. When complete dissolution was observed, the experiment was cooled to 55° C., and seeded with AP1189 succinate. 2% seed load was used, and it persisted with evidence of slurry formation. Post-seeding, stirring continued at 55° C. for 2 hours to allow experiment to equilibrate. The experiment was cooled to 5° C.
  • the diluted samples preparations were analysed by HPLC within 5 hours from preparation and the content of AP1189 was determined from the area under the curve by comparing to standard solutions of AP1189 acetate and AP1189 succinate respectively.
  • the solubilities of the test compounds at pH 1.2 are shown in Table 43.
  • the solubilities of the test compounds at pH 4.5 and pH 6.8 are shown in Table 44, where all purities were found to be within 92% and 95%.
  • the tosylate salt of AP1189 having XRPD pattern 1 was prepared by crystallisation from methanol.
  • the fumarate salt of AP1189 having XRPD pattern 1 was prepared by crystallisation from isopropylalcohol:water 90:10 v/v.
  • Naphthalene-1,5-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 ⁇ L 2-Propanol:water 90:10% v/v. A further 500 ⁇ L 2-Propanol:water 90:10% v/v was added to Naphthalene-1,5-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Naphthalene-1,5-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 ⁇ L THF. A further 500 ⁇ L of THF was added to Naphthalene-1,5-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 methylethyl ketone. Ethanesulfonic acid (1.1 molar equivalents) was transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L 2-Propanol:water (80:20% v/v). A further 500 ⁇ L of 2-Propanol:water (80:20% v/v) was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.).
  • Ethane-1,2-disulfonic having XRPD Acid Pattern 2 was prepared as follows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L methylethyl ketone. A further 500 ⁇ L of methylethyl ketone was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L THF. A further 500 ⁇ L of THF was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L 2-Propanol:water (80:20% v/v). A further 500 ⁇ L of 2-Propanol:water (80:20% v/v) was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L THF. A further 500 ⁇ L of THF was added to Cyclamic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Cyclamic Acid having XRPD Pattern 4 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L Acetone. A further 500 ⁇ L of Acetone was added to Cyclamic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L THF. A further 500 ⁇ L of THF was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD. After storage at 40° C./75% RH for 24 hours the diffractogram was consistent with pattern 5 by XRPD.
  • 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 by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 ⁇ L 2-Propanol:water 80:20% v/v. A further 500 ⁇ L of 2-Propanol:water 80:20% v/v was added to Oxalic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Oxalic Acid having XRPD Pattern 2 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L Acetone. A further 500 ⁇ L of Acetone was added to Oxalic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Oxalic Acid having XRPD Pattern 4 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L THF. A further 500 ⁇ L of THF was added to Oxalic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • (+)-Camphor-10-Sulfonic Acid having XRPD Pattern 1 was prepared as follows:
  • Ketoglutaric Acid having XRPD Pattern 1 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 1 mL of Acetone. Ketoglutaric acid (1.1 molar equivalents) was transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L methylethyl ketone. A further 500 ⁇ L of methylethyl ketone was added to DL-Mandelic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L Acetone. A further 500 ⁇ L of Acetone was added to DL-Mandelic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L methylethyl ketone. A further 500 ⁇ L of methylethyl ketone was added to Hippuric acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • 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 by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • L-Lactic Acid having XRPD Pattern 1 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L Acetone. A further 500 ⁇ L of Acetone was added to L-Lactic acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Glutaric Acid having XRPD Pattern 1 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L Acetone. A further 500 ⁇ L of Acetone was added to Glutaric acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Glutaric Acid having XRPD Pattern 2 was prepared as follows:
  • AP1189 Acetate 50 mg was weighed into a 1.5 mL HPLC vial and dissolved in 500 ⁇ L methylethyl ketone. A further 500 ⁇ L of methylethyl ketone was added to Glutaric acid (1.1 molar equivalents), which was then transferred by pipette into the API. The resulting mixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifuge filtration and analysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.
  • Adipic Acid having XRPD Pattern 1 was prepared as follows:
  • Infrared spectroscopy was carried out on a Bruker ALPHA P spectrometer. Sufficient material was placed onto the centre of the plate of the spectrometer and the spectra were obtained using the following parameters: Resolution: 4 cm ⁇ 1 ; Background Scan Time: 16 scans; Sample Scan Time: 16 scans; Data Collection: 4000 to 400 cm ⁇ 1 , Result Spectrum: Transmittance; Software: OPUS version 6.
  • Tables 45-68 show the FT-IR peak lists for various AP1189 salt polymorphs.
  • FIG. 92 shows the IR spectrum of AP1189 acetate Pattern 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Communicable Diseases (AREA)
  • Dermatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Virology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Pulmonology (AREA)
  • Hematology (AREA)
  • Transplantation (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Pyrrole Compounds (AREA)
US17/821,500 2021-06-21 2022-08-23 Polymorphs of phenyl pyrrole aminoguandium salts Pending US20230271922A9 (en)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
EP21180702 2021-06-21
EP21180708 2021-06-21
EP2118-0708.6 2021-06-21
EP21180702.9 2021-06-21
EP21180708.6 2021-06-21
EP21209855.2 2021-11-23
EP21209855 2021-11-23
PCT/EP2022/066884 WO2022268814A1 (en) 2021-06-21 2022-06-21 Salts of phenyl pyrrole aminoguanidine and polymorphs of phenyl pyrrole aminoguanidinium salts

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2022/066884 Continuation WO2022268814A1 (en) 2021-06-21 2022-06-21 Salts of phenyl pyrrole aminoguanidine and polymorphs of phenyl pyrrole aminoguanidinium salts

Publications (2)

Publication Number Publication Date
US20230002319A1 US20230002319A1 (en) 2023-01-05
US20230271922A9 true US20230271922A9 (en) 2023-08-31

Family

ID=84544160

Family Applications (2)

Application Number Title Priority Date Filing Date
US17/821,500 Pending US20230271922A9 (en) 2021-06-21 2022-08-23 Polymorphs of phenyl pyrrole aminoguandium salts
US18/065,702 Pending US20230114865A1 (en) 2021-06-21 2022-12-14 Phenyl pyrrole aminoguanidine salts and formulations

Family Applications After (1)

Application Number Title Priority Date Filing Date
US18/065,702 Pending US20230114865A1 (en) 2021-06-21 2022-12-14 Phenyl pyrrole aminoguanidine salts and formulations

Country Status (9)

Country Link
US (2) US20230271922A9 (ko)
EP (2) EP4359076A1 (ko)
JP (1) JP2024522817A (ko)
KR (2) KR20240024177A (ko)
AU (2) AU2022300305A1 (ko)
BR (1) BR112023026909A2 (ko)
CA (2) CA3220753A1 (ko)
IL (2) IL309104A (ko)
WO (2) WO2022268814A1 (ko)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023218048A1 (en) * 2022-05-12 2023-11-16 Synact Pharma Aps Resomelagon and its derivatives for the treatment of cardiovascular disease, hypertension and atherosclerosis

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2348016T3 (en) * 2006-06-09 2016-05-30 Synact Pharma Aps Phenylpyrrolaminoguanidine derivatives
KR102494613B1 (ko) * 2018-06-22 2023-02-06 신액트 파마 에이피에스 단백뇨의 치료
PT3773558T (pt) * 2019-05-10 2022-09-13 Synact Pharma Aps Tratamento combinado de doença artrítica
KR20220161315A (ko) * 2020-03-31 2022-12-06 신액트 파마 에이피에스 증후성 바이러스 질환의 치료

Also Published As

Publication number Publication date
CA3220756A1 (en) 2022-12-29
AU2022300305A1 (en) 2024-01-25
CA3220753A1 (en) 2022-12-29
KR20240024818A (ko) 2024-02-26
JP2024522817A (ja) 2024-06-21
EP4359383A1 (en) 2024-05-01
BR112023026909A2 (pt) 2024-03-05
EP4359076A1 (en) 2024-05-01
AU2022296767A1 (en) 2024-02-01
IL309104A (en) 2024-02-01
WO2022268825A1 (en) 2022-12-29
KR20240024177A (ko) 2024-02-23
IL309102A (en) 2024-02-01
WO2022268814A1 (en) 2022-12-29
US20230114865A1 (en) 2023-04-13
US20230002319A1 (en) 2023-01-05

Similar Documents

Publication Publication Date Title
US10301287B2 (en) Solid forms of cenicriviroc mesylate and processes of making solid forms of cenicriviroc mesylate
US20120029083A1 (en) Polymorphic forms of aliskiren hemifumarate and process for preparation thereof
US8865915B2 (en) Process for the preparation of the L-arginine salt of perindopril
US20230271922A9 (en) Polymorphs of phenyl pyrrole aminoguandium salts
US8329740B2 (en) Polymorphs of sunitinib malate
US20130296575A1 (en) Sunitinib and salts thereof and their polymorphs
US6806373B2 (en) Process for preparing leflunomide form I
KR102111248B1 (ko) 새로운 엠파글리플로진의 공결정
EP3820881B1 (en) Novel polymorphic forms of cyclo (-his-pro)
US20180273499A1 (en) Salts and solid state forms of vortioxetine
US20050222240A1 (en) Crystalline pyrazoles
JP2008174551A (ja) ラベプラゾールナトリウムの結晶形態
JP2024523459A (ja) フェニルピロールアミノグアニジンの塩及びフェニルピロールアミノグアニジウム塩の多形体
CN117836271A (zh) 苯基吡咯氨基胍的盐和苯基吡咯氨基胍鎓盐的多晶型物
WO2024133643A1 (en) Polymorph of phenyl pyrrole hydrazine carboximidamide compound
US7655800B2 (en) Crystalline 1H-imidazo[4,5-b]pyridin-5-amine, 7-[5-[(cyclohexylmethylamino)-methyl]-1H-indol-2-yl]-2-methyl, sulfate (1:1), trihydrate and its pharmaceutical uses
US9464086B2 (en) Crystalline forms of N,N-dicyclopropyl-4-(1,5-dimethyl-1 H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-D]pyrrolo[2,3-B]pyridine-7-carboxamide for the treatment of myeloproliferative disorders
RU2345994C2 (ru) МЕЗИЛАТ 4-(4-ТРАНС-ГИДРОКСИЦИКЛОГЕКСИЛ) АМИНО-2-ФЕНИЛ-7Н-ПИРРОЛО[2,3d] ПИРИМИДИНА И ЕГО ПОЛИМОРФНЫЕ ФОРМЫ (ВАРИАНТЫ)
US7232904B2 (en) Crystal of arylethenesulfonamide derivative and preparation process thereof
RU2573384C2 (ru) Новые полиморфы и соли
TWI335335B (en) A novel crystal of a triterpene derivative
KR102150825B1 (ko) 새로운 sglt-2 억제제의 신규한 공결정
US20040180953A1 (en) Crystalline form of phenylethanolamine, the preparation thereof and pharmaceutical compositions comprising the same
US20220089550A1 (en) Crystalline forms of (s)-2-(7-cyano-1h-benzimidazol-1 yl)-n-{1-[4-(1-cyano-1-methylethyl)phenyl]ethyl}acetamide
JP2018515477A (ja) 免疫調節薬の新規な結晶形

Legal Events

Date Code Title Description
AS Assignment

Owner name: SYNACT PHARMA APS, DENMARK

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BOESEN, THOMAS;JONASSEN, THOMAS ENGELBRECHT NORDKILD;REECE, HAYLEY ANN;AND OTHERS;SIGNING DATES FROM 20220706 TO 20220714;REEL/FRAME:060866/0132

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION