WO2024013058A1 - Salts of sco-101 and methods involving salts - Google Patents
Salts of sco-101 and methods involving salts Download PDFInfo
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- WO2024013058A1 WO2024013058A1 PCT/EP2023/068985 EP2023068985W WO2024013058A1 WO 2024013058 A1 WO2024013058 A1 WO 2024013058A1 EP 2023068985 W EP2023068985 W EP 2023068985W WO 2024013058 A1 WO2024013058 A1 WO 2024013058A1
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- sco
- xrpd
- cancer
- salt according
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present disclosure describes salts of SCO-101, crystals and amorphs thereof, as well as pharmaceutical compositions comprising the salts, methods for making them, and their use in treatment of cancer.
- SCO-101 also known as NS3728 was first described in WO 2000/24707.
- SCO- 101 has later been shown to be an effective potentiator of a range of anti-cancer agents and is currently being developed for cancer combination therapies, in particular for treatment of resistant cancers.
- WO 2017/198700 describes SCO-101 and its use in combination therapies for treatment of cancers.
- a range of substituted diphenyl ureas including SCO-101 can be prepared as described in WO 2000/24707 by mixing suitable starting materials soluble in toluene whereby SCO-101 precipitates when formed.
- SCO-101 prepared in toluene using the conditions of WO 2000/24707 is crystalline.
- SCO-101 forms a number of stable salts with non-toxic counterions, which are pharmacologically relevant.
- the properties of the salts developed vary, for example in terms of their stability, solubility, hygroscopicity and processibility rendering the salts suitable for different pharmacological purposes.
- Some of the salts are highly crystalline showing high thermal stability at varying relative humidity, rendering the crystalline salts important candidates for pharmaceutical development.
- sodium and ethylenediamine salts of SCO-101 including crystals thereof were found to exhibit significant differences in physical-chemical properties of high importance to the preparation of different medical formulations of SCO-101.
- the present disclosure thus provides SCO-10 salts and crystals thereof with different properties, such as some with increased solubility in water and in conditions simulating fasting/non-fasting in humans or some with increased thermal stability relative to other salts.
- the present disclosure provides a salt of SCO- 101 having increased water solubility.
- the present disclosure provides a salt of SCO-101 having increased thermal stability.
- the disclosure describes a salt comprising a compound of formula
- the present disclosure provides a process for preparing a salt comprising a compound of formula (SCO-101),
- the present disclosure provides a pharmaceutical composition
- a pharmaceutical composition comprising a salt of SCO-101 as defined herein; and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents
- the present disclosure provides a salt of SCO-101 as defined herein for use in the treatment of cancer.
- Figure 1 shows an XRPD Diffractogram of SCO-101 Potassium, Pattern 1.
- Figure 2 shows an XRPD Diffractogram of SCO-101 Sodium, Pattern 1.
- Figure 3 shows an XRPD Diffractogram of SCO-101 Zinc Methoxide, Pattern 2.
- Figure 4 shows an XRPD Diffractogram of SCO-101 L-Arginine, Pattern 1.
- Figure 5 shows an XRPD Diffractogram of SCO-101 Choline Hydroxide, Pattern 1.
- Figure 6 shows an XRPD Diffractogram of SCO-101 Diethylamine, Pattern 1.
- Figure 7 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 2.
- Figure 8 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 4.
- Figure 9 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 6.
- Figure 10 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 7.
- Figure 11 shows an XRPD Diffractogram of SCO-101 Ethylenediamine, Pattern 1.
- Figure 12 shows an XRPD Diffractogram of SCO-101 Benzathine, Pattern 1.
- Figure 13 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 1.
- Figure 14 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 2.
- Figure 15 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 3.
- Figure 16 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 4.
- Figure 17 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 5.
- Figure 18 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 6.
- Figure 19 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 7.
- Figure 20 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 8.
- Figure 21 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 1.
- Figure 22 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 2.
- Figure 23 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 3.
- Figure 24 shows an XRPD Diffractogram of SCO-101 2-(Dimethylamino)-Ethanol, Pattern 1.
- Figure 25 shows an XRPD Diffractogram of SCO-101 Olamine, Pattern 1.
- Figure 26 shows an XRPD Diffractogram of SCO-101 Epolamine, Pattern 1.
- Figure 27 shows an XRPD Diffractogram of SCO-101 Diolamine, Pattern 1.
- Figure 28 shows an XRPD Diffractogram of SCO-101 Ammonium Hydroxide, Pattern 1.
- Figure 29 shows an XRPD Diffractogram of SCO-101 Tromethamine, Pattern 4.
- Figure 30 shows an XRPD Diffractogram of SCO-101 Tromethamine, Pattern 5.
- Figure 31 shows an XRPD Diffractogram of SCO-101 Meglumine, Pattern 2.
- Figure 32 shows an XRPD Diffractogram of SCO-101 Sodium, Pattern 2.
- Figure 33 shows a summary of the primary salt screen - first page.
- Figure 34 shows a summary of the primary salt screen - second page.
- Figure 35 shows a summary of the primary salt screen - third page.
- Figure 36 shows a summary of the primary salt screen - fourth page.
- polymorph or "polymorphic form” used herein refers to a polymorphic form of a salt of SCO-101. Solids exist in either amorphous or crystalline forms also referred to as crystal forms herein. In the case of crystal forms, the crystal's molecules are positioned in 3-dimensional lattice sites. When a compound recrystallizes from a solution or slurry, it may crystallize with different spatial lattice arrangements, a property referred to as "polymorphism,” with the different crystal forms individually being referred to as a "polymorph”. Different polymorphic forms of a given substance may differ from each other with respect to one or more physical properties, such as solubility and dissociation, true density, crystal shape, compaction behavior, flow properties, and/or solid-state stability.
- each 2 Theta angle includes ⁇ 0.2° to account for error margins.
- a XRPD peak maximum defined by 2 Theta angle 10.0 will include 9.8 and 10.2, and any number in between, represented by 10.0 ⁇ 0.2.
- amorphous form refers to a non-crystalline form of a substance as determined by X-ray powder diffraction (XRPD).
- XRPD X-ray powder diffraction
- anti-cancer agent includes, but is not limited to, a chemotherapeutic agent, that has activity against a susceptible tumour.
- RH relative humidity
- hygroscopic is used herein to describe a compound or polymorphic form that sorbs water, either by absorption, adsorption, or a combination of the two processes.
- Pattern refers to a characteristic XRPD spectrum unique for a particular crystal form. A series of polymorphs for a given salt will thus referred to throughout the present disclosure by using Pattern and an integer. The specific XRPD patterns are illustrated in the figures.
- a salt comprising a compound of formula (SCO-101) is provided.
- the salt comprises one or more of the compound of formula (SCO- 101), and one or more counterions.
- the ratio between one or more of SCO-101 and one or more counterions depend for example on the valency of the counterion, such as that a monovalent cation will likely form a salt with one compound of formula (SCO-101), whereas a divalent cation will form a salt with two compounds of formula (SCO-101), or one compound of formula (SCO-101) and one further anion such that the net charge is zero.
- the counterion is monovalent, divalent, trivalent, or tetravalent, such as monovalent or divalent. In some embodiments, the counterion is organic or inorganic.
- the counterion comprises one or more alkali metals, one or more alkaline earth metals, and/or one or more transition metals. In one embodiment, the the countion is an alkali metal.
- the counterion is selected from the group consisting of: lithium, potassium, sodium, cesium, zinc, aluminum, chloroprocaine, procaine, triethylamine, histidine, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'- dibenzylethylenediamine, piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
- the counterion is obtained from a base as described in Example 1 herein.
- the counterion is selected from the group consisting of: potassium, sodium, zinc, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'- dibenzylethylenediamine, piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
- the counterion is selected from the group consisting of: sodium and ethylenediamine.
- the compound of SCO-101 is provided as a solvate with one or more solvent molecules, in particular as a salt comprising a counterion and one or more solvent molecules.
- the solvate is of a solvent selected from the group consisting of: water, 2-propanol, acetone, acetonitrile, ethanol, methanol, ethyl acetate, and tetrahydrafurane (THF).
- the salt is hydrated or anhydrous. In one embodiment, the salt is hydrated, such as a monohydrate, a dihydrate, a trihydrate, a tetrahydrate or a pentahydrate. In one embodiment, the salt is an anhydrate.
- the salt according to the present disclosure is provided in some embodiments as a crystalline salt, and in some embodiments as an anormph, i.e. is amorphous.
- the salt of the present disclosure is a potassium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, preferably a dihydrate.
- the potassium salt of SCO-101 is crystalline.
- the crystalline potassium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 1.
- the potassium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of:
- the salt of the present disclosure is a sodium salt of SCO-101, which is optionally an anhydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, or pentahydrate, such as a monohydrate or a pentahydrate.
- the sodium salt of SCO-101 was shown to be significantly more soluble in FaSSIF, i.e. an assay mimicking a fasting state, compared to both the free form and the ethylenediamine form.
- the SCO-101 sodium salt and crystals thereof can be useful in formulations where high solubility is desired.
- the sodium salt of SCO-101 was shown to display a relatively narrow polymorphic window, i.e. low variance in number of detected polymorphic forms relative to the other salts of SCO-101. In some cases, this is an important property for selecting a crystalline salt form for further clinical development.
- the sodium salt of SCO-101 is crystalline. In other embodiments, the sodium salt of SCO-101 is amorphous.
- the crystalline sodium salt of SCO-101 is characterized by XRPD 2- Theta peak maxima essentially as depicted in Figure 2 or 32.
- the sodium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 8.9 ⁇ 0.2°, 10.1 ⁇ 0.2°, 11.2 ⁇ 0.2°, 11.6 ⁇ 0.2°, 13.1 ⁇ 0.2°, 14 ⁇ 0.2°, 14.9 ⁇ 0.2°, 15.8 ⁇ 0.2°, 16.7 ⁇ 0.2°, 17.3 ⁇ 0.2°, 18 ⁇ 0.2°, 18.6 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.7 ⁇ 0.2°, 20.2 ⁇ 0.2°, 20.8 ⁇ 0.2°, 21.6 ⁇ 0.2°, 22.3 ⁇ 0.2°, 22.5 ⁇ 0.2°, 22.8 ⁇ 0.2°, 23.7 ⁇ 0.2°, 24.7 ⁇ 0.2°, 25.1 ⁇ 0.2°, 25.9 ⁇ 0.2°, 26.5 ⁇ 0.2°, 26.8
- the sodium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 8.9 ⁇ 0.2°, 10.1 ⁇ 0.2°, 11.2 ⁇ 0.2°, 11.6 ⁇ 0.2°, 13.1 ⁇ 0.2°, 14 ⁇ 0.2°, 14.9 ⁇ 0.2°, 15.8 ⁇ 0.2°, 16.7 ⁇ 0.2°, 17.3 ⁇ 0.2°, 18 ⁇ 0.2°, 18.6 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.7 ⁇ 0.2°, 20.2 ⁇ 0.2°, 20.8 ⁇ 0.2°, 21.6 ⁇ 0.2°, 22.3 ⁇ 0.2°, 22.5 ⁇ 0.2°, 22.8 ⁇ 0.2°, 23.7 ⁇ 0.2°, 24.7 ⁇ 0.2°, 25.1 ⁇ 0.2°, 25.9 ⁇ 0.2°, 26.5 ⁇ 0.2°, 26.8
- the sodium salt of SCO-101 is a hydrate, such as a pentahydrate.
- the pentahydrate is crystalline.
- the crystalline pentahydrate has XRPD 2-Theta peak maxima according to pattern 2 of [0038] of the present disclosure.
- the sodium salt of SCO-101 is a pentahydrate, such as a crystalline pentahydrate, and provides for increased solubility.
- the salt of the present disclosure is a zinc salt of SCO-101, which is optionally an anhydrate.
- the zinc salt of SCO-101 is crystalline.
- the zinc salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 3.
- the zinc salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 4.3 ⁇ 0.2°, 7.3 ⁇ 0.2°, 8.6 ⁇ 0.2°, 11.4 ⁇ 0.2°, 11.9 ⁇ 0.2°, 12.4 ⁇ 0.2°, 13 ⁇ 0.2°, 13.9 ⁇ 0.2°, 15.1 ⁇ 0.2°, 16.2 ⁇ 0.2°, 17.2 ⁇ 0.2°, 18.3 ⁇ 0.2°, 18.9 ⁇ 0.2°, 19.9 ⁇ 0.2°, 20.4 ⁇ 0.2°, 21.2 ⁇ 0.2°, 22.7 ⁇ 0.2°, 23.4 ⁇ 0.2°, 23.9 ⁇ 0.2°, 24.7 ⁇ 0.2°, 26.5 ⁇ 0.2°, 26.9 ⁇ 0.2°, 27.4 ⁇ 0.2°, 30.7 ⁇ 0.2°, 31.6 ⁇ 0.2°, 33.4 ⁇
- the salt of the present disclosure is an arginine salt of SCO-101, which is optionally a diarginine salt.
- the arginine salt of SCO-101 is crystalline.
- the arginine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 4.
- the arginine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.5 ⁇ 0.2°, 6.6 ⁇ 0.2°, 7.7 ⁇ 0.2°, 8.5 ⁇ 0.2°, 9.2 ⁇ 0.2°, 9.6 ⁇ 0.2°, 10.4 ⁇ 0.2°, 15 ⁇ 0.2°, 16.7 ⁇ 0.2°, 17.4 ⁇ 0.2°, 17.8 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.2 ⁇ 0.2°, 19.6 ⁇ 0.2°, 20.3 ⁇ 0.2°, 21.3 ⁇ 0.2°, 21.8 ⁇ 0.2°, 22.2 ⁇ 0.2°, 22.9 ⁇ 0.2°, 23.8 ⁇ 0.2°, 24.9 ⁇ 0.2°, 25.4 ⁇ 0.2°, 26 ⁇ 0.2°, 26.8 ⁇ 0.2°, 28.9 ⁇ 0.2°,
- the arginine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 4.1 ⁇ 0.2°, 6.2 ⁇ 0.2°, 8.2 ⁇ 0.2°, 10.7 ⁇ 0.2°, 11.3 ⁇ 0.2°, 12.8 ⁇ 0.2°, 13.2 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.8 ⁇ 0.2°, 16.4 ⁇ 0.2°, 17.7 ⁇ 0.2°, 18.2 ⁇ 0.2°, 18.6 ⁇ 0.2°, 19.2 ⁇ 0.2°, 19.5 ⁇ 0.2°, 19.9 ⁇ 0.2°, 20.5 ⁇ 0.2°, 21.5 ⁇ 0.2°, 22.4 ⁇ 0.2°, 23.1 ⁇ 0.2°, 23.9 ⁇ 0.2°, 24.5 ⁇ 0.2°, 25.3 ⁇ 0.2°, 25.7 ⁇ 0.2°, 26.1 ⁇ 0.2°,
- the salt of the present disclosure is a calcium salt of SCO-101.
- the calcium salt of SCO-101 is crystalline.
- the salt of the present disclosure is a choline salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate.
- the choline salt of SCO-101 is crystalline.
- the choline salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 5.
- the choline salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.2 ⁇ 0.2°, 9.8 ⁇ 0.2°, 10.4 ⁇ 0.2°, 11.7 ⁇ 0.2°, 12.7 ⁇ 0.2°, 13.7 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.1 ⁇ 0.2°, 16.7 ⁇ 0.2°,
- the salt of the present disclosure is a diethylamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate.
- the diethylamine salt of SCO-101 is crystalline.
- the diethylamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 6.
- the diethylamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.8 ⁇ 0.2°, 9.8 ⁇ 0.2°, 10 ⁇ 0.2°, 11.4 ⁇ 0.2°, 11.9 ⁇ 0.2°, 12.3 ⁇ 0.2°, 12.6 ⁇ 0.2°, 13 ⁇ 0.2°, 13.4 ⁇ 0.2°, 15.5 ⁇ 0.2°, 16.3 ⁇ 0.2°, 16.7 ⁇ 0.2°, 17.4 ⁇ 0.2°, 17.6 ⁇ 0.2°, 18 ⁇ 0.2°, 19.6 ⁇ 0.2°, 19.8 ⁇ 0.2°, 20 ⁇ 0.2°, 20.3 ⁇ 0.2°, 21.4 ⁇ 0.2°, 21.6 ⁇ 0.2°, 21.9 ⁇ 0.2°, 22.2 ⁇ 0.2°, 22.6 ⁇ 0.2°, 23 ⁇ 0.2°, 23.7 ⁇ 0.2°
- the salt of the present disclosure is a L-lysine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate.
- the L-lysine salt of SCO-101 is crystalline.
- the L-lysine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 7, 8, 9, or 10.
- the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 4.4 ⁇ 0.2°, 8.9 ⁇ 0.2°, 9.7 ⁇ 0.2°, 10.7 ⁇ 0.2°, 12.4 ⁇ 0.2°, 13.1 ⁇ 0.2°, 13.4 ⁇ 0.2°, 13.9 ⁇ 0.2°, 14 ⁇ 0.2°, 14.8 ⁇ 0.2°, 15.4 ⁇ 0.2°, 15.6 ⁇ 0.2°, 16.1 ⁇ 0.2°, 17.2 ⁇ 0.2°, 17.8 ⁇ 0.2°, 19.4 ⁇ 0.2°, 20.1 ⁇ 0.2°, 20.5 ⁇ 0.2°, 20.9 ⁇ 0.2°, 21.3 ⁇ 0.2°, 21.9 ⁇ 0.2°, 22.3 ⁇ 0.2°, 22.7 ⁇ 0.2°, 22.9 ⁇ 0.2°, 23.3 ⁇ 0.2°,
- the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 4.5 ⁇ 0.2°, 9.7 ⁇ 0.2°, 10.3 ⁇ 0.2°, 11.6 ⁇ 0.2°, 13.8 ⁇ 0.2°, 14.5 ⁇ 0.2°, 14.7 ⁇ 0.2°, 15.2 ⁇ 0.2°, 15.9 ⁇ 0.2°, 17.1 ⁇ 0.2°, 17.7 ⁇ 0.2°, 18.1 ⁇ 0.2°, 18.6 ⁇ 0.2°, 18.9 ⁇ 0.2°, 19.4 ⁇ 0.2°, 19.6 ⁇ 0.2°,
- the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 3.5 ⁇ 0.2°, 10.1 ⁇ 0.2°, 10.3 ⁇ 0.2°, 11 ⁇ 0.2°, 12.2 ⁇ 0.2°, 13.5 ⁇ 0.2°, 14.1 ⁇ 0.2°, 14.3 ⁇ 0.2°, 15.4 ⁇ 0.2°, 15.9 ⁇ 0.2°, 16.5 ⁇ 0.2°, 19 ⁇ 0.2°, 19.6 ⁇ 0.2°, 19.8 ⁇ 0.2°, 20.4 ⁇ 0.2°, 20.9 ⁇ 0.2°, 21.2 ⁇ 0.2°, 22.1 ⁇ 0.2°, 22.7 ⁇ 0.2°, 23.3 ⁇ 0.2°, 23.7 ⁇ 0.2°, 24.4 ⁇ 0.2°, 24.9 ⁇ 0.2°, 25.5 ⁇ 0.2°, 27 ⁇ 0.2°, 27.
- the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4 ⁇ 0.2°, 4.7 ⁇ 0.2°, 8.1 ⁇ 0.2°, 11.4 ⁇ 0.2°, 12.1 ⁇ 0.2°, 12.6 ⁇ 0.2°, 13 ⁇ 0.2°, 13.4 ⁇ 0.2°,
- the salt of the present disclosure is an ethylenediamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the ethylenediamine salt of SCO-101 is crystalline. As shown in Example 2, the ethylenediamine salt of SCO-101 is fully stable at room temperature, 40 °C and even at 80 °C. This supports that the ethylenediamine salt and in particular crystals thereof display increased thermal stability compared to other salt variants of SCO-101.
- the ethylenediamine salt of SCO-101 was shown to display a relatively narrow polymorphic window, i.e. low variance in number of detected polymorphic forms relative to the other salts of SCO-101. In some cases, this is an important property for selecting a crystalline salt form for further clinical development.
- the ethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 11.
- the ethylenediamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 7.2 ⁇ 0.2°, 9.7 ⁇ 0.2°, 10.6 ⁇ 0.2°, 10.8 ⁇ 0.2°, 11.3 ⁇ 0.2°, 13.3 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.5 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.2 ⁇ 0.2°, 17.2 ⁇ 0.2°, 18.2 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.1 ⁇ 0.2°, 19.8 ⁇ 0.2°, 20.1 ⁇ 0.2°,
- the salt of the present disclosure is a N,N'-dibenzylethylenediamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the N,N'-dibenzylethylenediamine salt of SCO-101 is crystalline.
- the N,N'-dibenzylethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 12.
- the N,N'-dibenzylethylenediamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.7 ⁇ 0.2°, 7.1 ⁇ 0.2°, 9.2 ⁇ 0.2°, 10.9 ⁇ 0.2°, 11.2 ⁇ 0.2°, 11.5 ⁇ 0.2°, 12 ⁇ 0.2°, 12.6 ⁇ 0.2°, 13.6 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.6 ⁇ 0.2°, 15.4 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.8 ⁇ 0.2°, 17 ⁇ 0.2°, 17.2 ⁇ 0.2°,
- the salt of the present disclosure is a piperazine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the piperazine salt of SCO-101 is crystalline.
- the piperazine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 13, 14, 15, 16, 17, 18, 19, or 20.
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.4 ⁇ 0.2°, 9.2 ⁇ 0.2°, 9.4 ⁇ 0.2°, 10.2 ⁇ 0.2°, 10.9 ⁇ 0.2°, 11.3 ⁇ 0.2°, 12.4 ⁇ 0.2°, 12.7 ⁇
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 6.3 ⁇ 0.2°, 9.3 ⁇ 0.2°, 9.6 ⁇ 0.2°, 10 ⁇ 0.2°, 10.6 ⁇ 0.2°, 11.2 ⁇ 0.2°, 11.8 ⁇ 0.2°, 12 ⁇ 0.2°,
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 3.3 ⁇ 0.2°, 5.9 ⁇ 0.2°, 9.5 ⁇ 0.2°, 9.9 ⁇ 0.2°, 10.7 ⁇ 0.2°, 11.1 ⁇ 0.2°, 12.3 ⁇ 0.2°, 14.2 ⁇
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 9.2 ⁇ 0.2°, 10 ⁇ 0.2°, 11.6 ⁇ 0.2°, 12 ⁇ 0.2°, 14 ⁇ 0.2°, 15.9 ⁇ 0.2°, 16.2 ⁇ 0.2°, 16.7 ⁇ 0.2°,
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 6.2 ⁇ 0.2°, 9.3 ⁇ 0.2°, 10 ⁇ 0.2°, 10.6 ⁇ 0.2°, 11.8 ⁇ 0.2°, 12.2 ⁇ 0.2°, 12.4 ⁇ 0.2°, 14.4 ⁇ 0.2°, 15.1 ⁇ 0.2°, 17 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19 ⁇ 0.2°, 19.3 ⁇ 0.2°, 20.1 ⁇ 0.2°, 20.6 ⁇ 0.2°, 20.9 ⁇ 0.2°, 21.3
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 5.5 ⁇ 0.2°, 7.9 ⁇ 0.2°, 8.1 ⁇ 0.2°, 9.3 ⁇ 0.2°, 10.3 ⁇ 0.2°, 11.3 ⁇ 0.2°, 12.6 ⁇ 0.2°, 13.1 ⁇ 0.2°, 13.6 ⁇ 0.2°, 15 ⁇ 0.2°, 16 ⁇ 0.2°, 16.8 ⁇ 0.2°, 17.6 ⁇ 0.2°, 18.1 ⁇ 0.2°, 18.6 ⁇ 0.2°, 19 ⁇ 0.2°, 20.2 ⁇ 0.2°, 20.7 ⁇ 0.2°, 21.3 ⁇ 0.2°, 21.5 ⁇ 0.2°, 21.8 ⁇ 0.2°, 22.5 ⁇ 0.2°, 22.7 ⁇ 0.2°, 23.1 ⁇ 0.2°, 23.7 ⁇ 0.2°, 23.9 ⁇
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4.2 ⁇ 0.2°, 6.1 ⁇ 0.2°, 7.3 ⁇ 0.2°, 8.4 ⁇ 0.2°, 9.9 ⁇ 0.2°, 11.2 ⁇ 0.2°, 11.6 ⁇ 0.2°, 12.6 ⁇ 0.2°, 13.3 ⁇ 0.2°, 14.6 ⁇ 0.2°, 15.2 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.3 ⁇ 0.2°, 17.5 ⁇ 0.2°, 18.4 ⁇ 0.2°, 19 ⁇ 0.2°, 19.4 ⁇ 0.2°, 20 ⁇ 0.2°, 20.4 ⁇ 0.2°, 20.7 ⁇ 0.2°, 20.9 ⁇ 0.2°, 21.9 ⁇ 0.2°, 22.5 ⁇ 0.2°, 22.7 ⁇ 0.2°, 23.4 ⁇ 0.2°, 23.8
- the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 8 selected from the group consisting of: 5.5 ⁇ 0.2°, 7.1 ⁇ 0.2°, 8.2 ⁇ 0.2°, 10.8 ⁇ 0.2°, 11.4 ⁇ 0.2°, 12 ⁇ 0.2°, 12.8 ⁇ 0.2°, 13.3 ⁇ 0.2°,
- the salt of the present disclosure is a 2-(diethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate.
- the 2-(diethylamino)-ethanol salt of SCO-101 is crystalline.
- the 2-(diethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 21, 22, or 23.
- the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5 ⁇ 0.2°, 5.1 ⁇ 0.2°, 9.3 ⁇ 0.2°, 10.6 ⁇ 0.2°, 10.7 ⁇ 0.2°, 12.3 ⁇ 0.2°, 14.3 ⁇ 0.2°,
- the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 3.3 ⁇ 0.2°, 5.7 ⁇ 0.2°, 5.9 ⁇ 0.2°, 6 ⁇ 0.2°, 6.1 ⁇ 0.2°, 6.9 ⁇ 0.2°, 7.1 ⁇ 0.2°, 7.3 ⁇ 0.2°, 12.1 ⁇ 0.2°, 13.9 ⁇ 0.2°, 14.1 ⁇ 0.2°, 15.3 ⁇ 0.2°, 16.1 ⁇ 0.2°, 16.2 ⁇ 0.2°, 16.6 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.3 ⁇ 0.2°, 19.7 ⁇ 0.2°, 20.4 ⁇ 0.2°, 20.5 ⁇ 0.2°, 21.5 ⁇ 0.2°, 22.3 ⁇ 0.2°, 22.9 ⁇ 0.2°, 23.5 ⁇ 0.2°, 23.8
- the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 6.5 ⁇ 0.2°, 7.9 ⁇ 0.2°, 8.1 ⁇ 0.2°, 8.3 ⁇ 0.2°, 11.1 ⁇ 0.2°, 12.1 ⁇ 0.2°, 12.6 ⁇ 0.2°,
- the salt of the present disclosure is a 2-(dimethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate.
- the 2-(dimethylamino)-ethanol salt of SCO-101 is crystalline.
- the 2-(dimethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 24.
- the 2-(dimethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ⁇ 0.2°, 11 ⁇ 0.2°, 11.6 ⁇ 0.2°, 14.1 ⁇ 0.2°, 15.1 ⁇ 0.2°, 15.5 ⁇ 0.2°, 17.7 ⁇ 0.2°, 18 ⁇ 0.2°, 18.3 ⁇ 0.2°, 18.8 ⁇ 0.2°, 19.5 ⁇ 0.2°, 19.7 ⁇ 0.2°, 20 ⁇ 0.2°, 20.3 ⁇ 0.2°, 20.4 ⁇ 0.2°, 20.7 ⁇ 0.2°, 21.2 ⁇ 0.2°, 22.2 ⁇ 0.2°, 22.5 ⁇ 0.2°, 22.8 ⁇ 0.2°, 23.1 ⁇ 0.2°, 23.7 ⁇ 0.2°, 25.4 ⁇ 0.2°, 25.6 ⁇ 0.2°, 26.2 ⁇ 0.2°
- the salt of the present disclosure is an ethanolamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the ethanolamine salt of SCO-101 is crystalline.
- the ethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 25.
- the ethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ⁇ 0.2°, 10.6 ⁇ 0.2°, 10.9 ⁇ 0.2°, 11.3 ⁇ 0.2°, 13.3 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.8 ⁇ 0.2°, 16 ⁇ 0.2°, 17.4 ⁇ 0.2°, 19 ⁇ 0.2°, 19.2 ⁇ 0.2°, 19.7 ⁇ 0.2°, 20.4 ⁇ 0.2°, 21.3 ⁇ 0.2°, 21.5 ⁇ 0.2°, 22 ⁇ 0.2°, 22.2 ⁇ 0.2°, 22.4 ⁇ 0.2°, 23.5 ⁇ 0.2°, 24.1 ⁇ 0.2°, 24.3 ⁇ 0.2°, 24.7 ⁇ 0.2°, 25.7 ⁇ 0.2°, 25.8 ⁇ 0.2°, 26.6 ⁇ 0.2°, 26.8 ⁇
- the salt of the present disclosure is a 2-(hydroxyethyl)-pyrrolidine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is crystalline.
- the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 26.
- the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.4 ⁇ 0.2°, 6.5 ⁇ 0.2°, 8.3 ⁇ 0.2°, 8.6 ⁇ 0.2°, 11.2 ⁇ 0.2°, 12.8 ⁇ 0.2°, 14.2 ⁇ 0.2°, 14.4 ⁇ 0.2°, 14.9 ⁇ 0.2°, 15.6 ⁇ 0.2°, 16.6 ⁇ 0.2°, 17.7 ⁇ 0.2°, 18.4 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.4 ⁇ 0.2°, 19.8 ⁇ 0.2°, 20.1 ⁇ 0.2°, 20.5 ⁇ 0.2°, 20.9 ⁇ 0.2°, 21.1 ⁇ 0.2°, 21.5 ⁇ 0.2°, 22.3 ⁇ 0.2°, 22.6 ⁇ 0.2°, 23.2 ⁇ 0.2°, 23.5
- the salt of the present disclosure is a diethanolamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
- the diethanolamine salt of SCO-101 is crystalline.
- the diethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 27.
- the diethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 8 ⁇ 0.2°, 10.6 ⁇ 0.2°, 11.2 ⁇ 0.2°, 12 ⁇ 0.2°, 12.6 ⁇ 0.2°, 12.9 ⁇ 0.2°, 13.5 ⁇ 0.2°, 14.9 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.8 ⁇ 0.2°, 17.8 ⁇ 0.2°, 18.1 ⁇ 0.2°, 18.3 ⁇ 0.2°, 19 ⁇ 0.2°, 19.6 ⁇ 0.2°, 19.9 ⁇ 0.2°, 20.6 ⁇ 0.2°, 21.3 ⁇ 0.2°, 21.9 ⁇ 0.2°, 22.1 ⁇ 0.2°, 22.5 ⁇ 0.2°, 23.2 ⁇ 0.2°, 23.5 ⁇ 0.2°, 24 ⁇ 0.2°, 24.2 ⁇ 0.2°, 24.6 ⁇ 0.2°,
- the salt of the present disclosure is an ammonium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate. In some embodiments, the ammonium salt of SCO-101 is crystalline.
- ammonium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 28.
- the ammonium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.5 ⁇ 0.2°, 9.3 ⁇ 0.2°, 9.8 ⁇ 0.2°, 10.8 ⁇ 0.2°, 12.3 ⁇ 0.2°, 13.4 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.6 ⁇ 0.2°, 15.6 ⁇ 0.2°, 16.4 ⁇ 0.2°, 17.1 ⁇ 0.2°, 18.2 ⁇ 0.2°, 18.7 ⁇ 0.2°, 19.1 ⁇ 0.2°, 19.4 ⁇ 0.2°, 19.8 ⁇ 0.2°, 20.5 ⁇ 0.2°, 21.2 ⁇ 0.2°, 22 ⁇ 0.2°, 23 ⁇ 0.2°, 23.5 ⁇ 0.2°, 23.9 ⁇ 0.2°, 24.1 ⁇ 0.2°, 24.8 ⁇ 0.2°, 25.1 ⁇ 0.2°, 25.5 ⁇ 0.2°, 25.5 ⁇ 0.2
- the salt of the present disclosure is a tromethamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate.
- the tromethamine salt of SCO-101 is crystalline.
- the tromethamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 29 or 30.
- the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 6.6 ⁇ 0.2°, 7.5 ⁇ 0.2°, 10.8 ⁇ 0.2°, 12 ⁇ 0.2°, 13.6 ⁇ 0.2°, 13.9 ⁇ 0.2°, 14.5 ⁇ 0.2°, 15 ⁇ 0.2°, 15.7 ⁇ 0.2°, 17.2 ⁇ 0.2°, 18 ⁇ 0.2°, 19 ⁇ 0.2°, 19.5 ⁇ 0.2°, 20 ⁇ 0.2°, 20.5 ⁇ 0.2°, 21.2 ⁇ 0.2°, 21.6 ⁇ 0.2°, 22.9 ⁇ 0.2°, 23.2 ⁇ 0.2°, 23.5 ⁇ 0.2°, 24.4 ⁇ 0.2°, 25 ⁇ 0.2°, 26.3 ⁇ 0.2°, 26.9 ⁇ 0.2°, 27.4 ⁇ 0.2°,
- the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 4.4 ⁇ 0.2°, 5.7 ⁇ 0.2°, 6.7 ⁇ 0.2°, 6.9 ⁇ 0.2°, 7.4 ⁇ 0.2°, 8.9 ⁇ 0.2°, 9.2 ⁇ 0.2°, 11.4 ⁇ 0.2°, 11.9 ⁇ 0.2°, 13.4 ⁇ 0.2°, 14.1 ⁇ 0.2°, 14.3 ⁇ 0.2°, 14.7 ⁇ 0.2°, 14.9 ⁇ 0.2°, 15.5 ⁇ 0.2°, 15.9 ⁇ 0.2°,
- the salt of the present disclosure is an N-methyl glucamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate.
- the N- methyl glucamine salt of SCO-101 is crystalline.
- the N-methyl glucamine salt of SCO-101 is characterized by XRPD 2- Theta peak maxima essentially as depicted in Figure 31.
- the N-methyl glucamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.9 ⁇ 0.2°, 6.9 ⁇ 0.2°, 7.6 ⁇ 0.2°, 8.9 ⁇ 0.2°, 9.3 ⁇ 0.2°, 11 ⁇ 0.2°, 11.4 ⁇ 0.2°, 12.2 ⁇ 0.2°, 13.4 ⁇ 0.2°, 14 ⁇ 0.2°, 14.8 ⁇ 0.2°, 15.1 ⁇ 0.2°, 15.7 ⁇ 0.2°, 16.3 ⁇ 0.2°, 16.8 ⁇ 0.2°, 17.7 ⁇ 0.2°, 17.9 ⁇
- the salts of SCO-101 as described herein can be prepared for example as described in Example 1.
- a process is provided for preparing a salt comprising a compound of formula (SCO-101),
- the solution or suspension is in one or more of: 2-propanol, acetone, ethanol, ethyl acetate, tetrahydrofurane, and/or acetonitrile.
- the base is selected from the group consisting of: potassium hydroxide, sodium hydroxide, zinc methoxide, zinc ethoxide, arginine, calcium hydroxide, magnesium hydroxide, choline hydroxide, diethylamine, lysine, ethylenediamine, N,N'-dibenzylethylenediamine (benzathine), piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol (deanol), ethanolamine (olamine), 2-(hydroxyethyl)-pyrrolidine (epolamine), diethanolamine (diolamine), ammonium hydroxide, tromethamine, and N-methyl glucamine (meglumine).
- the salt is dried prior to or after isolation, optionally wherein the salt is dried under vacuum.
- the salt is dried at from 25 °C to 80 °C, such as at 40°C prior to or after isolation, optionally wherein the salt is dried under vacuum.
- a pharmaceutical composition comprising a salt of SCO- 101 as defined herein; and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents.
- a salt of SCO-101 as defined herein is provided for use in the treatment of cancer.
- a method for treatment of cancer comprising administering a salt of SCO-101 as defined herein to a patient having a cancer.
- the treatment further comprises administering one or more anticancer agents to a patient having cancer.
- the salt of SCO-101 is administered to the patient daily.
- the one or more anti-cancer agents are selected from the group consisting of topoisomerase inhibitors, anti-hormone agents, alkylating agents, mitotic inhibitors, antimetabolites, anti-tumor antibiotics, corticosteroids, targeted anti-cancer therapy, differentiating agents and immunotherapy.
- the anti-cancer agent is administered in combination with one or more further anti-cancer agents.
- the anti-cancer agent is a topoisomerase I inhibitor or topoisomerase II inhibitor.
- the anti-cancer agent is a topoisomerase I inhibitor selected from the group consisting of: irinotecan, its active metabolite SN-38, and topotecan.
- anti-cancer agent is an anti-hormone agent which is: a. an anti-estrogen selected from the group consisting of: fulvestrant, tamoxifen, toremifene, and clomifene, or b. an anti-progestogen selected from the group consisting of: mifepristone, ulipristal acetate, aglepristone, lilopristone and onapristone.
- the anti-estrogen is fulvestrant or tamoxifen. In one embodiment, the anti-progestogen is onapristone.
- the anti-cancer agent is an alkylating agent which is: a. a nitrogen mustard selected from the group consisting of: mechlorethamine, chlorambucil, cyclophosphamide, ifosfamide, and melphalan, b. a nitrosourea selected from the group consisting of: streptozocin, carmustine, and lomustine, c. an alkyl sulfonate which is busulfan, d. a triazine selected from the group consisting of: dacarbazine (DTIC) and temozolomide, or e. an ethylenimine selected from the group consisting of: thiotepa and altretamine
- the alkylating agent is temozolomide.
- Antimetabolites are temozolomide.
- the anti-cancer agent is an antimetabolite selected from the group consisting of: 5-fluorouracil, 6-mercaptopurine, Capecitabine, Cytarabine, Floxuridine, Fludarabine, Gemcitabine, Hydroxyurea, Methotrexate, and Pemetrexed.
- the antimetabolite is 5-fluorouracil or gemcitabine.
- the anti-cancer agent is a mitotic inhibitor which is: a. a taxane selected from the group consisting of: paclitaxel and docetaxel; b. ixabepilone; c. a vinca alkaloid selected from the group consisting of: vinblastine, vincristine, and vinorelbine; or d. estramustine.
- the mitotic inhibitor is paclitaxel or docetaxel.
- the anti-cancer agent is administered in combination with one or more further anti-cancer agents.
- the anti-cancer agent is administered in combination with a further anticancer agent which is 5-fluorouracil. In one embodiment, the anti-cancer agent is administered in combination with 5-fluorouracil and folinic acid. In one embodiment, the anti-cancer agent is irinotecan and administered in combination with 5-fluorouracil and folinic acid.
- the anti-cancer agent is an immunotherapy agent.
- Immunotherapy drugs are given to people with cancer to help their immune systems recognize and attack cancer cells.
- Active immunotherapies stimulate the body's own immune system to fight the disease.
- Passive immunotherapies do not rely on the body to attack the disease; they're immune system components (such as antibodies) created outside the body and given to fight the cancer.
- Examples of active immunotherapies include:
- Monoclonal antibody therapy such as rituximab (Rituxan®) and alemtuzumab
- Non-specific immunotherapies and adjuvants other substances or cells that boost the immune response
- BCG interleukin-2
- IL-2 interleukin-2
- interferon-alfa interleukin-2
- Immunomodulating drugs such as thalidomide and lenalidomide (Revlimid®)
- the anti-cancer agent is a PD-1 or PD-L1 inhibitor, such as an antibody capable of inhibiting PD-1 or PD-L1.
- Cancer vaccines are a type of active specific immunotherapy.
- the anticancer agent is a cancer vaccine.
- the cancer is a solid tumour or a leukemia.
- the cancer is a solid tumour, such as a solid tumour selected from sarcoma, carcinoma and lymphoma.
- the cancer is selected from the group consisting of colorectal cancer, breast cancer, lung cancer (non small cell lung cancer and small cell lung cancer), one or more glioblastomas, one or more Head and neck cancers, one or more malignant melanomas, basal cell skin cancer, squamous cell skin cancer, liver cancer, pancreatic cancer, prostate cancer, anal cancer, cervix uteri cancer, bladder cancer, corpus uteri cancer, ovarian cancer, gall bladder cancer, one or more sarcomas, one or more leukemias (myeloid and lymphatic), one or more lymphomas, myelomatosis, cholangiocarcinoma, gastric cancer, testicular cancer, uveal cancer, mesothelioma, merkel cell carcinoma, and one or more myelodysplastic syndromes (MDS).
- MDS myelodysplastic syndromes
- the cancer is metastatic cancer.
- the cancer is colorectal cancer, such as metastatic colorectal cancer.
- the leukemia is acute myeloid leukemia (AML).
- the cancer is pancreatic cancer, such as metastatic pancreatic cancer.
- the cancer is breast cancer, such as metastatic breast cancer.
- the cancer is a resistant cancer which is resistant to the anti-cancer agent when administered alone.
- the resistance is de novo resistance. In some embodiments, the resistance is acquired resistance.
- Chemicals used in the examples herein, e.g. for buffers and substrates, are commercial products of at least reagent grade.
- 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:
- VH-XRPD Variable Humidity X-ray Powder Diffraction
- thermodynamic form of SCO-101 i.e. SCO-101 form I was prepared as follows: SCO- 101 (50 g, 1.0 eq., 101 mmol) was dissolved in 2-propanol (257 g) in a 1 L reactor. The reaction mixture was heated at 50 °C until a clear solution was obtained. To the solution, water (326 g) was added portion wise over a period of 30 min. After cooling the resulting slurry to 20 °C over a period of 1 h SCO-101 crude was isolated by filtration.
- the filter cake was washed with a mixture of 2- propanol/water (50/50% w/w, 39 g) before SCO-101 crude was re-dissolved in acetone (154 g) at 10 ⁇ 5 °C. To the solution was then added water (195 g) over a period of 70 to 90 min. The crystallized SCO-101 was isolated and washed with a mixture of acetone/water (45:55% w/w, 180 g). The product, SCO-101 form I was dried in an oven under reduced pressure at 45 °C.
- Table 2 Selected solvents for salt formation experiments • A magnetic stirrer bar was added to all experiments and the vials were capped and sealed with parafilm. The experiments were temperature cycled as follows:
- the present example demonstrates the successful preparation of a range of salts of SCO-101, including crystals and amorphs thereof.
- the crystals have distinguishable XRPD patterns, and the salts including the crystals, and amorphs thereof are potential candidates for pharmaceutical development.
- the present example demonstrates that the sodium and ethylenediamine salts of SCO-101 are stable at room temperature and 40 °C. Further, the ethylenediamine salt of SCO-101 was shown to be fully stable even at 80 °C. This supports that the ethylenediamine salt and in particular crystals thereof display increased thermal stability.
- thermodynamic solubility determination was carried out on SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1 in buffers at pH 1.2, 4.5, and 7.4 as well as in FaSSIF and FeSSIF. The procedure was as follows:
- SCO-101 crystal form I was also subjected to thermodynamic solubility determination: 100 pL aliquots of both FaSSIF and FeSSIF buffers were added to 10 mg of SCO-101 Form 1 in 2 mL vials until a total of 1 mL was added. The pH of the slurries was measured. The experiments were agitated at 37°C for 24 hrs in an incubator/shaker. After 24 hrs, observations were made on the FaSSIF and FeSSIF slurries and pH was measured. The slurries were then centrifuged, and the solids were analyzed by XRPD and compared against the received SCO-101. The saturated solutions were then analyzed by HPLC to assess the concentration of SCO-101.
- HPLC analysis determined the solubility at 37 °C was below 0.002 mg/mL for both salts at pH 1.2 and 4.5 and below 0.001 mg/mL at pH 7.4.
- the solubility of the sodium salt was determined to be 0.45 mg/mL in FaSSIF and 1.1 mg/mL in FeSSIF (a difference of 0.65 mg/mL).
- the solubility of the ethylenediamine salt was determined to be 0.04 mg/mL in FaSSIF and 1.6 mg/mL in FeSSIF (a difference of 1.56 mg/mL).
- the present example demonstrates that the free acid, the sodium salt, and the ethylenediamine salt of SCO-101 display significantly different solubilities.
- the sodium salt of SCO-101 in particular was shown to be significantly more soluble in FaSSIF, i.e. an assay mimicking a fasting state, compared to both the free form and the ethylenediamine form.
- the ethylenediamine salt Pattern 1 experiment was a slurry after 24 hours so this was filtered centrifugally (0.22 pm Nylon filter, 2 min, 10000 RPM) and the solid analysed by XRPD.
Abstract
The present invention describes salts of SCO-101, crystals and amorphs thereof, as well as pharmaceutical compositions comprising the salts, methods for making them, and their use in treatment of cancer.
Description
Salts of SCO-101 and methods involving salts
Technical Field
[0001] The present disclosure describes salts of SCO-101, crystals and amorphs thereof, as well as pharmaceutical compositions comprising the salts, methods for making them, and their use in treatment of cancer.
Background
[0002] Cancer is an overwhelming burden to our society with approximately 18 million new cases of cancer diagnosed in 2019. Despite the introduction of many new treatment modalities/options, de novo or acquired resistance to the applied treatments still represents the major cause of death from cancer.
[0003] The compound SCO-101, also known as NS3728 was first described in WO 2000/24707. SCO- 101 has later been shown to be an effective potentiator of a range of anti-cancer agents and is currently being developed for cancer combination therapies, in particular for treatment of resistant cancers. WO 2017/198700 describes SCO-101 and its use in combination therapies for treatment of cancers.
[0004] A range of substituted diphenyl ureas including SCO-101 can be prepared as described in WO 2000/24707 by mixing suitable starting materials soluble in toluene whereby SCO-101 precipitates when formed. SCO-101 prepared in toluene using the conditions of WO 2000/24707 is crystalline.
Summary
[0005] The present inventors have found that SCO-101 forms a number of stable salts with non-toxic counterions, which are pharmacologically relevant. The properties of the salts developed vary, for example in terms of their stability, solubility, hygroscopicity and processibility rendering the salts suitable for different pharmacological purposes. Some of the salts are highly crystalline showing high thermal stability at varying relative humidity, rendering the crystalline salts important candidates for pharmaceutical development. In addition, sodium and ethylenediamine salts of SCO-101 including crystals thereof were found to exhibit significant differences in physical-chemical properties of high importance to the preparation of different medical formulations of SCO-101. The present disclosure thus provides SCO-10 salts and crystals thereof with different properties, such as some with increased
solubility in water and in conditions simulating fasting/non-fasting in humans or some with increased thermal stability relative to other salts. In some cases, the present disclosure provides a salt of SCO- 101 having increased water solubility. In some embodiments, the present disclosure provides a salt of SCO-101 having increased thermal stability.
[0006] Accordingly, in a first aspect the disclosure describes a salt comprising a compound of formula
(SCO-101), or a solvate thereof, and a counterion.
[0007] In a further aspect, the present disclosure provides a process for preparing a salt comprising a compound of formula (SCO-101),
(SCO-101), or a solvate thereof, and a counterion; wherein the process comprises the steps of: a. providing a solution or suspension of the compound, b. mixing the solution or suspension of the compound with a base to obtain the salt, c. isolating the salt.
[0008] In a further aspect, the present disclosure provides a pharmaceutical composition comprising a salt of SCO-101 as defined herein; and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents
[0009] In a further aspect, the present disclosure provides a salt of SCO-101 as defined herein for use
in the treatment of cancer.
Description of drawings and figures
[0010] The figures included herein are illustrative and simplified for clarity, and they merely show details which are essential to the understanding of the invention, while other details may have been left out. Throughout the specification, claims and drawings the same reference numerals are used for identical or corresponding parts. In the figures and drawing included herein:
Figure 1 shows an XRPD Diffractogram of SCO-101 Potassium, Pattern 1.
Figure 2 shows an XRPD Diffractogram of SCO-101 Sodium, Pattern 1.
Figure 3 shows an XRPD Diffractogram of SCO-101 Zinc Methoxide, Pattern 2.
Figure 4 shows an XRPD Diffractogram of SCO-101 L-Arginine, Pattern 1.
Figure 5 shows an XRPD Diffractogram of SCO-101 Choline Hydroxide, Pattern 1.
Figure 6 shows an XRPD Diffractogram of SCO-101 Diethylamine, Pattern 1.
Figure 7 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 2.
Figure 8 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 4.
Figure 9 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 6.
Figure 10 shows an XRPD Diffractogram of SCO-101 L-Lysine, Pattern 7.
Figure 11 shows an XRPD Diffractogram of SCO-101 Ethylenediamine, Pattern 1.
Figure 12 shows an XRPD Diffractogram of SCO-101 Benzathine, Pattern 1.
Figure 13 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 1.
Figure 14 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 2.
Figure 15 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 3.
Figure 16 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 4.
Figure 17 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 5.
Figure 18 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 6.
Figure 19 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 7.
Figure 20 shows an XRPD Diffractogram of SCO-101 Piperazine, Pattern 8.
Figure 21 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 1.
Figure 22 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 2.
Figure 23 shows an XRPD Diffractogram of SCO-101 2-(Diethylamino)-Ethanol, Pattern 3.
Figure 24 shows an XRPD Diffractogram of SCO-101 2-(Dimethylamino)-Ethanol, Pattern 1.
Figure 25 shows an XRPD Diffractogram of SCO-101 Olamine, Pattern 1.
Figure 26 shows an XRPD Diffractogram of SCO-101 Epolamine, Pattern 1.
Figure 27 shows an XRPD Diffractogram of SCO-101 Diolamine, Pattern 1.
Figure 28 shows an XRPD Diffractogram of SCO-101 Ammonium Hydroxide, Pattern 1.
Figure 29 shows an XRPD Diffractogram of SCO-101 Tromethamine, Pattern 4.
Figure 30 shows an XRPD Diffractogram of SCO-101 Tromethamine, Pattern 5.
Figure 31 shows an XRPD Diffractogram of SCO-101 Meglumine, Pattern 2.
Figure 32 shows an XRPD Diffractogram of SCO-101 Sodium, Pattern 2.
Figure 33 shows a summary of the primary salt screen - first page.
Figure 34 shows a summary of the primary salt screen - second page.
Figure 35 shows a summary of the primary salt screen - third page.
Figure 36 shows a summary of the primary salt screen - fourth page.
Incorporation by reference
[0011] All publications, patents, and patent applications referred to herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event of a conflict between a term herein and a term in an incorporated reference, the term herein prevails and controls.
Detailed Description
[0012] The features and advantages of the present invention is readily apparent to a person skilled in the art by the below detailed description of embodiments and examples of the invention with reference to the figures and drawings included herein.
Definitions
[0013] The term "polymorph" or "polymorphic form" used herein refers to a polymorphic form of a salt of SCO-101. Solids exist in either amorphous or crystalline forms also referred to as crystal forms herein. In the case of crystal forms, the crystal's molecules are positioned in 3-dimensional lattice sites. When a compound recrystallizes from a solution or slurry, it may crystallize with different spatial lattice arrangements, a property referred to as "polymorphism," with the different crystal forms individually being referred to as a "polymorph". Different polymorphic forms of a given substance may differ from each other with respect to one or more physical properties, such as solubility and dissociation, true density, crystal shape, compaction behavior, flow properties, and/or solid-state stability.
[0014] Unless otherwise specified, the unit of 2 Theta angles is degrees (°). When the 2 Theta angles
are used to characterize a polymorph's distinctive XRPD peak maxima, each 2 Theta angle includes ±0.2° to account for error margins. Thus, a XRPD peak maximum defined by 2 Theta angle 10.0 will include 9.8 and 10.2, and any number in between, represented by 10.0±0.2.
[0015] The term "amorphous form" as used herein, refers to a non-crystalline form of a substance as determined by X-ray powder diffraction (XRPD). The term "amorphous" form cover solids of disordered arrangements of molecules and do not possess a distinguishable crystal lattice.
[0016] The term "anti-cancer agent" as used herein includes, but is not limited to, a chemotherapeutic agent, that has activity against a susceptible tumour.
[0017] The term "relative humidity" or "RH" refers to the ratio in percentage of the partial pressure of water vapor to the equilibrium vapor pressure of water at a given temperature.
[0018] The term "hygroscopic" is used herein to describe a compound or polymorphic form that sorbs water, either by absorption, adsorption, or a combination of the two processes.
[0019] The term "Pattern" used herein refer to a characteristic XRPD spectrum unique for a particular crystal form. A series of polymorphs for a given salt will thus referred to throughout the present disclosure by using Pattern and an integer. The specific XRPD patterns are illustrated in the figures.
General classes of salts
(SCO-101), or a solvate thereof, and a counterion.
[0021] In some embodiments, the salt comprises one or more of the compound of formula (SCO- 101), and one or more counterions. The ratio between one or more of SCO-101 and one or more counterions depend for example on the valency of the counterion, such as that a monovalent cation
will likely form a salt with one compound of formula (SCO-101), whereas a divalent cation will form a salt with two compounds of formula (SCO-101), or one compound of formula (SCO-101) and one further anion such that the net charge is zero.
[0022] In some embodiments, the counterion is monovalent, divalent, trivalent, or tetravalent, such as monovalent or divalent. In some embodiments, the counterion is organic or inorganic.
[0023] In some embodiments, the counterion comprises one or more alkali metals, one or more alkaline earth metals, and/or one or more transition metals. In one embodiment, the the countion is an alkali metal.
[0024] In some embodiments, wherein the counterion is selected from the group consisting of: lithium, potassium, sodium, cesium, zinc, aluminum, chloroprocaine, procaine, triethylamine, histidine, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'- dibenzylethylenediamine, piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
[0025] In some embodiments, the counterion is obtained from a base as described in Example 1 herein. In some embodiments, the counterion is selected from the group consisting of: potassium, sodium, zinc, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'- dibenzylethylenediamine, piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
[0026] In some embodiments, the counterion is selected from the group consisting of: sodium and ethylenediamine.
Solvates
[0027] In some embodiments, the compound of SCO-101 is provided as a solvate with one or more solvent molecules, in particular as a salt comprising a counterion and one or more solvent molecules.
[0028] In some embodiments, the solvate is of a solvent selected from the group consisting of: water, 2-propanol, acetone, acetonitrile, ethanol, methanol, ethyl acetate, and tetrahydrafurane (THF).
[0029] In some embodiments, the salt is hydrated or anhydrous. In one embodiment, the salt is hydrated, such as a monohydrate, a dihydrate, a trihydrate, a tetrahydrate or a pentahydrate. In one embodiment, the salt is an anhydrate.
Crystals and amorphs
[0030] The salt according to the present disclosure is provided in some embodiments as a crystalline salt, and in some embodiments as an anormph, i.e. is amorphous.
Potassium salt
[0031] In one embodiment, the salt of the present disclosure is a potassium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, preferably a dihydrate.
[0032] In some embodiments, the potassium salt of SCO-101 is crystalline. In some embodiments, the crystalline potassium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 1.
[0033] In some embodiments, the potassium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of:
10.4 ± 0.2°, 10.8 ± 0.2°, 11.9 ± 0.2°, 12.8 ± 0.2°, 13.1 ± 0.2°, 14.1 ± 0.2°, 15.8 ± 0.2°, 17.4 ± 0.2°, 18.2 ± 0.2°, 19.8 ± 0.2°, 20.4 ± 0.2°, 20.9 ± 0.2°, 22.2 ± 0.2°, 22.9 ± 0.2°, 24 ± 0.2°, 24.6 ± 0.2°, 25.7 ± 0.2°, 26.3 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.6 ± 0.2°, 30.1 ± 0.2°, 31.1 ± 0.2°, 31.8 ± 0.2°, 32.6 ± 0.2°, 33.1 ± 0.2°,
34.5 ± 0.2°, 35.5 ± 0.2°, 36.4 ± 0.2°, 37.2 ± 0.2°, 38.4 ± 0.2°, 39.8 ± 0.2°, 42.6 ± 0.2°, 43.4 ± 0.2°, 44.4 ± 0.2°, and 45.2 ± 0.2°.
Sodium salt
[0034] In one embodiment, the salt of the present disclosure is a sodium salt of SCO-101, which is optionally an anhydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, or pentahydrate, such as a monohydrate or a pentahydrate. As demonstrated in Example 2, the sodium salt of SCO-101 was shown to be significantly more soluble in FaSSIF, i.e. an assay mimicking a fasting state, compared to both the free form and the ethylenediamine form. Further as shown in Example 2, the SCO-101 sodium salt and crystals thereof can be useful in formulations where high solubility is desired. In addition, the sodium salt of SCO-101 was shown to display a relatively narrow polymorphic window, i.e. low variance in number of detected polymorphic forms relative to the other salts of SCO-101. In some
cases, this is an important property for selecting a crystalline salt form for further clinical development.
[0035] In some embodiments, the sodium salt of SCO-101 is crystalline. In other embodiments, the sodium salt of SCO-101 is amorphous.
[0036] In some embodiments, the crystalline sodium salt of SCO-101 is characterized by XRPD 2- Theta peak maxima essentially as depicted in Figure 2 or 32.
[0037] In some embodiments, the sodium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 8.9 ± 0.2°, 10.1 ± 0.2°, 11.2 ± 0.2°, 11.6 ± 0.2°, 13.1 ± 0.2°, 14 ± 0.2°, 14.9 ± 0.2°, 15.8 ± 0.2°, 16.7 ± 0.2°, 17.3 ± 0.2°, 18 ± 0.2°, 18.6 ± 0.2°, 18.7 ± 0.2°, 19.7 ± 0.2°, 20.2 ± 0.2°, 20.8 ± 0.2°, 21.6 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.7 ± 0.2°, 24.7 ± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°, 26.8 ± 0.2°, 27.1 ± 0.2°, 27.6 ± 0.2°, 28.2 ± 0.2°, 28.9 ± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.3 ± 0.2°, 32 ± 0.2°, 32.7 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 35 ± 0.2°, 35.8 ± 0.2°, 36.8 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.9 ± 0.2°, 41.4 ± 0.2°, 42 ± 0.2°, 42.8 ± 0.2°, 44.5 ± 0.2°, and 46.9 ± 0.2°.
[0038] In some embodiments, the sodium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 8.9 ± 0.2°, 10.1 ± 0.2°, 11.2 ± 0.2°, 11.6 ± 0.2°, 13.1 ± 0.2°, 14 ± 0.2°, 14.9 ± 0.2°, 15.8 ± 0.2°, 16.7 ± 0.2°, 17.3 ± 0.2°, 18 ± 0.2°, 18.6 ± 0.2°, 18.7 ± 0.2°, 19.7 ± 0.2°, 20.2 ± 0.2°, 20.8 ± 0.2°, 21.6 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.7 ± 0.2°, 24.7 ± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°, 26.8 ± 0.2°, 27.1 ± 0.2°, 27.6 ± 0.2°, 28.2 ± 0.2°, 28.9 ± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.3 ± 0.2°, 32 ± 0.2°, 32.7 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 35 ± 0.2°, 35.8 ± 0.2°, 36.8 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.9 ± 0.2°, 41.4 ± 0.2°, 42 ± 0.2°, 42.8 ± 0.2°, 44.5 ± 0.2°, 46.9 ± 0.2°.
[0039] In some embodiments, the sodium salt of SCO-101 is a hydrate, such as a pentahydrate. In some embodiments, the pentahydrate is crystalline. In some embodiments, the crystalline pentahydrate has XRPD 2-Theta peak maxima according to pattern 2 of [0038] of the present disclosure. In some embodiments, the sodium salt of SCO-101 is a pentahydrate, such as a crystalline pentahydrate, and provides for increased solubility.
Zinc salt
[0040] In some embodiments, the salt of the present disclosure is a zinc salt of SCO-101, which is optionally an anhydrate. In some embodiments, the zinc salt of SCO-101 is crystalline.
[0041] In some embodiments, the zinc salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 3.
[0042] In some embodiments, the zinc salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 4.3 ± 0.2°, 7.3 ± 0.2°, 8.6 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 12.4 ± 0.2°, 13 ± 0.2°, 13.9 ± 0.2°, 15.1 ± 0.2°, 16.2 ± 0.2°, 17.2 ± 0.2°, 18.3 ± 0.2°, 18.9 ± 0.2°, 19.9 ± 0.2°, 20.4 ± 0.2°, 21.2 ± 0.2°, 22.7 ± 0.2°, 23.4 ± 0.2°, 23.9 ± 0.2°, 24.7 ± 0.2°, 26.5 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 30.7 ± 0.2°, 31.6 ± 0.2°, 33.4 ± 0.2°, 34.3 ± 0.2°, 36 ± 0.2°, 39.6 ± 0.2°, and 43.4 ± 0.2°.
Arginine salt
[0043] In some embodiments, the salt of the present disclosure is an arginine salt of SCO-101, which is optionally a diarginine salt. In some embodiments, the arginine salt of SCO-101 is crystalline.
[0044] In some embodiments, the arginine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 4.
[0045] In some embodiments, the arginine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.5 ± 0.2°, 6.6 ± 0.2°, 7.7 ± 0.2°, 8.5 ± 0.2°, 9.2 ± 0.2°, 9.6 ± 0.2°, 10.4 ± 0.2°, 15 ± 0.2°, 16.7 ± 0.2°, 17.4 ± 0.2°, 17.8 ± 0.2°, 18.7 ± 0.2°, 19.2 ± 0.2°, 19.6 ± 0.2°, 20.3 ± 0.2°, 21.3 ± 0.2°, 21.8 ± 0.2°, 22.2 ± 0.2°, 22.9 ± 0.2°, 23.8 ± 0.2°, 24.9 ± 0.2°, 25.4 ± 0.2°, 26 ± 0.2°, 26.8 ± 0.2°, 28.9 ± 0.2°, 33.9 ± 0.2°, 34.9 ± 0.2°, 36.9 ± 0.2°, 38.4 ± 0.2°, and 41.3 ± 0.2°.
[0046] In some embodiments, the arginine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 4.1 ± 0.2°, 6.2 ± 0.2°, 8.2 ± 0.2°, 10.7 ± 0.2°, 11.3 ± 0.2°, 12.8 ± 0.2°, 13.2 ± 0.2°, 14.3 ± 0.2°, 14.8 ± 0.2°, 16.4 ± 0.2°, 17.7 ± 0.2°, 18.2 ± 0.2°, 18.6 ± 0.2°, 19.2 ± 0.2°, 19.5 ± 0.2°, 19.9 ± 0.2°, 20.5 ± 0.2°, 21.5 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 23.9 ± 0.2°, 24.5 ± 0.2°, 25.3 ± 0.2°, 25.7 ± 0.2°, 26.1 ± 0.2°, 26.4 ± 0.2°, 27.3 ± 0.2°, 28 ± 0.2°, 28.9 ± 0.2°, 29.8 ± 0.2°, 31 ± 0.2°, 31.5 ± 0.2°, 32.7 ± 0.2°, 33.2
± 0.2°, 34.5 ± 0.2°, 35.9 ± 0.2°, 39.2 ± 0.2°, 40.6 ± 0.2°, 41.6 ± 0.2°, 43.3 ± 0.2°, and 45.2 ± 0.2°.
Calcium salt
[0047] In some embodiments, the salt of the present disclosure is a calcium salt of SCO-101. In some embodiments, the calcium salt of SCO-101 is crystalline.
Choline salt
[0048] In some embodiments, the salt of the present disclosure is a choline salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate. In some embodiments, the choline salt of SCO-101 is crystalline.
[0049] In some embodiments, the choline salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 5.
[0050] In some embodiments, the choline salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.2 ± 0.2°, 9.8 ± 0.2°, 10.4 ± 0.2°, 11.7 ± 0.2°, 12.7 ± 0.2°, 13.7 ± 0.2°, 15.7 ± 0.2°, 16.1 ± 0.2°, 16.7 ± 0.2°,
17.6 ± 0.2°, 17.8 ± 0.2°, 18.2 ± 0.2°, 18.9 ± 0.2°, 19.6 ± 0.2°, 20.8 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 22.2 ±
0.2°, 22.6 ± 0.2°, 22.9 ± 0.2°, 23.1 ± 0.2°, 23.5 ± 0.2°, 23.9 ± 0.2°, 24.5 ± 0.2°, 24.8 ± 0.2°, 25.2 ± 0.2°,
25.6 ± 0.2°, 26 ± 0.2°, 26.6 ± 0.2°, 27.1 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31.3 ±
0.2°, 31.7 ± 0.2°, 32.6 ± 0.2°, 33.5 ± 0.2°, 34.2 ± 0.2°, 34.7 ± 0.2°, 35.5 ± 0.2°, 36.9 ± 0.2°, 39.6 ± 0.2°,
40.6 ± 0.2°, 41.7 ± 0.2°, 42.6 ± 0.2°, 43.7 ± 0.2°, 45.3 ± 0.2°, and 48.2 ± 0.2°.
Diethylamine salt
[0051] In some embodiments, the salt of the present disclosure is a diethylamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate. In some embodiments, the diethylamine salt of SCO-101 is crystalline.
[0052] In some embodiments, the diethylamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 6.
[0053] In some embodiments, the diethylamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.8 ± 0.2°, 9.8 ± 0.2°, 10 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 12.3 ± 0.2°, 12.6 ± 0.2°, 13 ± 0.2°, 13.4 ± 0.2°, 15.5 ± 0.2°, 16.3 ± 0.2°, 16.7 ± 0.2°, 17.4 ± 0.2°, 17.6 ± 0.2°, 18 ± 0.2°, 19.6 ± 0.2°, 19.8 ±
0.2°, 20 ± 0.2°, 20.3 ± 0.2°, 21.4 ± 0.2°, 21.6 ± 0.2°, 21.9 ± 0.2°, 22.2 ± 0.2°, 22.6 ± 0.2°, 23 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 24.8 ± 0.2°, 25.4 ± 0.2°, 26 ± 0.2°, 26.3 ± 0.2°, 26.8 ± 0.2°, 27.2 ± 0.2°,
27.4 ± 0.2°, 27.8 ± 0.2°, 28.3 ± 0.2°, 28.7 ± 0.2°, 29.6 ± 0.2°, 30.5 ± 0.2°, 31 ± 0.2°, 32.1 ± 0.2°, 32.6 ±
0.2°, 33 ± 0.2°, 34 ± 0.2°, 34.7 ± 0.2°, 35.6 ± 0.2°, 36 ± 0.2°, 36.5 ± 0.2°, 37.4 ± 0.2°, 38.4 ± 0.2°, 39.1 ±
0.2°, 40.2 ± 0.2°, 40.8 ± 0.2°, 41.8 ± 0.2°, 42.8 ± 0.2°, 43.4 ± 0.2°, 44.1 ± 0.2°, 45.4 ± 0.2°, 46.5 ± 0.2°,
47.6 ± 0.2°, and 48.3 ± 0.2°.
Lysine salt
[0054] In some embodiments, the salt of the present disclosure is a L-lysine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate. In some embodiments, the L-lysine salt of SCO-101 is crystalline.
[0055] In some embodiments, the L-lysine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 7, 8, 9, or 10.
[0056] In some embodiments, the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 4.4 ± 0.2°, 8.9 ± 0.2°, 9.7 ± 0.2°, 10.7 ± 0.2°, 12.4 ± 0.2°, 13.1 ± 0.2°, 13.4 ± 0.2°, 13.9 ± 0.2°, 14 ± 0.2°, 14.8 ± 0.2°, 15.4 ± 0.2°, 15.6 ± 0.2°, 16.1 ± 0.2°, 17.2 ± 0.2°, 17.8 ± 0.2°, 19.4 ± 0.2°, 20.1 ± 0.2°, 20.5 ± 0.2°, 20.9 ± 0.2°, 21.3 ± 0.2°, 21.9 ± 0.2°, 22.3 ± 0.2°, 22.7 ± 0.2°, 22.9 ± 0.2°, 23.3 ± 0.2°,
23.7 ± 0.2°, 24.2 ± 0.2°, 24.7 ± 0.2°, 25.2 ± 0.2°, 26.1 ± 0.2°, 26.4 ± 0.2°, 27.1 ± 0.2°, 27.9 ± 0.2°, 28.3 ±
0.2°, 29.7 ± 0.2°, 30.8 ± 0.2°, 31.2 ± 0.2°, 32.2 ± 0.2°, 33.3 ± 0.2°, 34.3 ± 0.2°, 34.9 ± 0.2°, 35.6 ± 0.2°,
36.1 ± 0.2°, 37.1 ± 0.2°, 37.5 ± 0.2°, 38.8 ± 0.2°, 39.7 ± 0.2°, 40.3 ± 0.2°, 43.4 ± 0.2°, 45.5 ± 0.2°, 46.6 ±
0.2°, 47.2 ± 0.2°.
[0057] In some embodiments, the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 4.5 ± 0.2°, 9.7 ± 0.2°, 10.3 ± 0.2°, 11.6 ± 0.2°, 13.8 ± 0.2°, 14.5 ± 0.2°, 14.7 ± 0.2°, 15.2 ± 0.2°, 15.9 ± 0.2°, 17.1 ± 0.2°, 17.7 ± 0.2°, 18.1 ± 0.2°, 18.6 ± 0.2°, 18.9 ± 0.2°, 19.4 ± 0.2°, 19.6 ± 0.2°,
20.9 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 22 ± 0.2°, 22.5 ± 0.2°, 23 ± 0.2°, 23.4 ± 0.2°, 24.3 ± 0.2°, 24.9 ± 0.2°, 26 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 27.8 ± 0.2°, 28.6 ± 0.2°, 29 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31.4 ± 0.2°,
32.9 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 34.5 ± 0.2°, 36.2 ± 0.2°, 37.1 ± 0.2°, 38.6 ± 0.2°, 39.3 ± 0.2°, 41.7 ± 0.2°, 43.4 ± 0.2°, 44.6 ± 0.2°, 46 ± 0.2°, 47.1 ± 0.2°, and 49 ± 0.2°.
[0058] In some embodiments, the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 3.5 ± 0.2°, 10.1 ± 0.2°, 10.3 ± 0.2°, 11 ± 0.2°, 12.2 ± 0.2°, 13.5 ± 0.2°, 14.1 ± 0.2°, 14.3 ± 0.2°, 15.4 ± 0.2°, 15.9 ± 0.2°, 16.5 ± 0.2°, 19 ± 0.2°, 19.6 ± 0.2°, 19.8 ± 0.2°, 20.4 ± 0.2°, 20.9 ± 0.2°, 21.2 ± 0.2°, 22.1 ± 0.2°, 22.7 ± 0.2°, 23.3 ± 0.2°, 23.7 ± 0.2°, 24.4 ± 0.2°, 24.9 ± 0.2°, 25.5 ± 0.2°, 27 ± 0.2°, 27.8 ± 0.2°, 28.3 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31 ± 0.2°, 31.6 ± 0.2°, 32.3 ± 0.2°, 33.2 ± 0.2°, 34.5 ± 0.2°, 36.4 ± 0.2°, 38 ± 0.2°, 38.6 ± 0.2°, 39.1 ± 0.2°, 45.6 ± 0.2°, 46.6 ± 0.2°, and 47.9 ± 0.2°.
[0059] In some embodiments, the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4 ± 0.2°, 4.7 ± 0.2°, 8.1 ± 0.2°, 11.4 ± 0.2°, 12.1 ± 0.2°, 12.6 ± 0.2°, 13 ± 0.2°, 13.4 ± 0.2°,
14.3 ± 0.2°, 14.9 ± 0.2°, 15.7 ± 0.2°, 16.2 ± 0.2°, 17.6 ± 0.2°, 17.9 ± 0.2°, 19 ± 0.2°, 19.8 ± 0.2°, 20.3 ±
0.2°, 20.7 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 21.7 ± 0.2°, 22.1 ± 0.2°, 22.4 ± 0.2°, 22.6 ± 0.2°, 23.2 ± 0.2°,
23.3 ± 0.2°, 23.7 ± 0.2°, 24.2 ± 0.2°, 24.4 ± 0.2°, 24.9 ± 0.2°, 25.4 ± 0.2°, 25.7 ± 0.2°, 26.8 ± 0.2°, 27 ±
0.2°, 27.7 ± 0.2°, 29.1 ± 0.2°, 29.5 ± 0.2°, 30 ± 0.2°, 30.8 ± 0.2°, 31.4 ± 0.2°, 32.1 ± 0.2°, 33.5 ± 0.2°, 34.5 ± 0.2°, 35.2 ± 0.2°, 35.8 ± 0.2°, 36.6 ± 0.2°, 37 ± 0.2°, 37.6 ± 0.2°, 38 ± 0.2°, 38.6 ± 0.2°, 40.4 ± 0.2°, 41 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 43.8 ± 0.2°, 44.2 ± 0.2°, 45.4 ± 0.2°, 45.9 ± 0.2°, 46.6 ± 0.2°, 47.7 ± 0.2°, and 48.5 ± 0.2°.
Ethylenediamine salt
[0060] In some embodiments, the salt of the present disclosure is an ethylenediamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the ethylenediamine salt of SCO-101 is crystalline. As shown in Example 2, the ethylenediamine salt of SCO-101 is fully stable at room temperature, 40 °C and even at 80 °C. This supports that the ethylenediamine salt and in particular crystals thereof display increased thermal stability compared to other salt variants of SCO-101. In addition, the ethylenediamine salt of SCO-101 was shown to display a relatively narrow polymorphic window, i.e. low variance in number of detected polymorphic forms relative to the other salts of SCO-101. In some cases, this is an important property for selecting a crystalline salt form for further clinical development.
[0061] In some embodiments, the ethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 11.
[0062] In some embodiments, the ethylenediamine salt of SCO-101 when measured using Cu Ka
radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 7.2 ± 0.2°, 9.7 ± 0.2°, 10.6 ± 0.2°, 10.8 ± 0.2°, 11.3 ± 0.2°, 13.3 ± 0.2°, 14.3 ± 0.2°, 14.5 ± 0.2°, 15.7 ± 0.2°, 16.2 ± 0.2°, 17.2 ± 0.2°, 18.2 ± 0.2°, 18.7 ± 0.2°, 19.1 ± 0.2°, 19.8 ± 0.2°, 20.1 ± 0.2°,
21.4 ± 0.2°, 21.9 ± 0.2°, 22.2 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 24.2 ± 0.2°, 24.6 ±
0.2°, 25.6 ± 0.2°, 26.1 ± 0.2°, 26.7 ± 0.2°, 26.7 ± 0.2°, 27.1 ± 0.2°, 27.4 ± 0.2°, 27.9 ± 0.2°, 28.9 ± 0.2°,
29.4 ± 0.2°, 29.8 ± 0.2°, 30 ± 0.2°, 30.4 ± 0.2°, 30.6 ± 0.2°, 30.8 ± 0.2°, 32 ± 0.2°, 32.9 ± 0.2°, 33.9 ± 0.2°,
34.2 ± 0.2°, 34.9 ± 0.2°, 35.6 ± 0.2°, 36.8 ± 0.2°, 37.6 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.6 ± 0.2°, 40.3 ±
0.2°, 41.2 ± 0.2°, 41.5 ± 0.2°, 42.6 ± 0.2°, 43.1 ± 0.2°, 43.6 ± 0.2°, 44.9 ± 0.2°, 46.1 ± 0.2°, 46.8 ± 0.2°, and 48.7 ± 0.2°.
Dibenzylethylenediamine salt
[0063] In some embodiments, the salt of the present disclosure is a N,N'-dibenzylethylenediamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the N,N'-dibenzylethylenediamine salt of SCO-101 is crystalline.
[0064] In some embodiments, the N,N'-dibenzylethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 12.
[0065] In some embodiments, the N,N'-dibenzylethylenediamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.7 ± 0.2°, 7.1 ± 0.2°, 9.2 ± 0.2°, 10.9 ± 0.2°, 11.2 ± 0.2°, 11.5 ± 0.2°, 12 ± 0.2°, 12.6 ± 0.2°, 13.6 ± 0.2°, 14.3 ± 0.2°, 14.6 ± 0.2°, 15.4 ± 0.2°, 15.7 ± 0.2°, 16.8 ± 0.2°, 17 ± 0.2°, 17.2 ± 0.2°,
17.7 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.5 ± 0.2°, 20.3 ± 0.2°, 20.5 ± 0.2°, 21 ± 0.2°, 21.4 ± 0.2°, 21.8 ±
0.2°, 22.4 ± 0.2°, 22.7 ± 0.2°, 22.9 ± 0.2°, 23.5 ± 0.2°, 24.3 ± 0.2°, 24.6 ± 0.2°, 24.9 ± 0.2°, 25.5 ± 0.2°,
26 ± 0.2°, 26.5 ± 0.2°, 27 ± 0.2°, 27.3 ± 0.2°, 27.8 ± 0.2°, 28.7 ± 0.2°, 29.5 ± 0.2°, 30.3 ± 0.2°, 30.5 ± 0.2°,
30.9 ± 0.2°, 31.1 ± 0.2°, 31.6 ± 0.2°, 32.2 ± 0.2°, 32.6 ± 0.2°, 32.9 ± 0.2°, 33.7 ± 0.2°, 34.4 ± 0.2°, 35.8 ± 0.2°, 36.4 ± 0.2°, 37.3 ± 0.2°, 38.2 ± 0.2°, 38.9 ± 0.2°, 39.6 ± 0.2°, 40.1 ± 0.2°, 40.8 ± 0.2°, 41.3 ± 0.2°,
41.7 ± 0.2°, 42.6 ± 0.2°, 43.3 ± 0.2°, 43.9 ± 0.2°, 44.8 ± 0.2°, and 48.3 ± 0.2°.
Piperazine salt
[0066] In some embodiments, the salt of the present disclosure is a piperazine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the piperazine salt of SCO-101 is crystalline.
[0067] In some embodiments, the piperazine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 13, 14, 15, 16, 17, 18, 19, or 20.
[0068] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.4 ± 0.2°, 9.2 ± 0.2°, 9.4 ± 0.2°, 10.2 ± 0.2°, 10.9 ± 0.2°, 11.3 ± 0.2°, 12.4 ± 0.2°, 12.7 ±
0.2°, 13.6 ± 0.2°, 14.1 ± 0.2°, 16.3 ± 0.2°, 16.6 ± 0.2°, 17.3 ± 0.2°, 17.7 ± 0.2°, 18.6 ± 0.2°, 19.3 ± 0.2°,
19.9 ± 0.2°, 20.4 ± 0.2°, 21 ± 0.2°, 21.3 ± 0.2°, 21.6 ± 0.2°, 21.8 ± 0.2°, 22.3 ± 0.2°, 22.7 ± 0.2°, 23.5 ±
0.2°, 24 ± 0.2°, 24.4 ± 0.2°, 24.6 ± 0.2°, 25.5 ± 0.2°, 25.8 ± 0.2°, 26.1 ± 0.2°, 26.7 ± 0.2°, 27.9 ± 0.2°, 28.1 ± 0.2°, 28.8 ± 0.2°, 29.4 ± 0.2°, 29.7 ± 0.2°, 30.2 ± 0.2°, 30.7 ± 0.2°, 31.5 ± 0.2°, 32.1 ± 0.2°, 33.4 ± 0.2°,
33.8 ± 0.2°, 34.5 ± 0.2°, 35 ± 0.2°, 35.8 ± 0.2°, 36.4 ± 0.2°, 37.9 ± 0.2°, 38.4 ± 0.2°, 39.1 ± 0.2°, 39.4 ± 0.2°, 40.1 ± 0.2°, 41.1 ± 0.2°, 41.7 ± 0.2°, 42.7 ± 0.2°, 43.5 ± 0.2°, 44.6 ± 0.2°, 46.6 ± 0.2°, 47.5 ± 0.2°, and 49 ± 0.2°.
[0069] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 6.3 ± 0.2°, 9.3 ± 0.2°, 9.6 ± 0.2°, 10 ± 0.2°, 10.6 ± 0.2°, 11.2 ± 0.2°, 11.8 ± 0.2°, 12 ± 0.2°,
12.2 ± 0.2°, 12.4 ± 0.2°, 13.3 ± 0.2°, 13.7 ± 0.2°, 14.6 ± 0.2°, 15.2 ± 0.2°, 16.2 ± 0.2°, 17 ± 0.2°, 17.7 ±
0.2°, 18.1 ± 0.2°, 18.4 ± 0.2°, 18.6 ± 0.2°, 19.3 ± 0.2°, 19.5 ± 0.2°, 20.1 ± 0.2°, 20.6 ± 0.2°, 20.9 ± 0.2°,
21.3 ± 0.2°, 21.7 ± 0.2°, 22 ± 0.2°, 22.2 ± 0.2°, 22.6 ± 0.2°, 22.9 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.3 ±
0.2°, 25.2 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°, 27.1 ± 0.2°, 27.5 ± 0.2°, 28.1 ± 0.2°, 29 ± 0.2°, 29.6 ± 0.2°, 30.1
± 0.2°, 31.1 ± 0.2°, 32 ± 0.2°, 33.2 ± 0.2°, 35.9 ± 0.2°, 36.6 ± 0.2°, 37.1 ± 0.2°, 37.9 ± 0.2°, 39.1 ± 0.2°,
40.1 ± 0.2°, 40.9 ± 0.2°, 42.1 ± 0.2°, 43.4 ± 0.2°, and 47.6 ± 0.2°.
[0070] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 3.3 ± 0.2°, 5.9 ± 0.2°, 9.5 ± 0.2°, 9.9 ± 0.2°, 10.7 ± 0.2°, 11.1 ± 0.2°, 12.3 ± 0.2°, 14.2 ±
0.2°, 14.6 ± 0.2°, 15.3 ± 0.2°, 16.1 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°, 17.9 ± 0.2°, 18.9 ± 0.2°, 19.7 ± 0.2°,
20.1 ± 0.2°, 20.4 ± 0.2°, 21.2 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°, 22.3 ± 0.2°, 22.6 ± 0.2°, 23.6 ± 0.2°, 23.9 ±
0.2°, 24.2 ± 0.2°, 24.7 ± 0.2°, 24.9 ± 0.2°, 25.2 ± 0.2°, 25.9 ± 0.2°, 27.3 ± 0.2°, 27.9 ± 0.2°, 28.6 ± 0.2°,
28.9 ± 0.2°, 29.8 ± 0.2°, 30.2 ± 0.2°, 30.6 ± 0.2°, 31 ± 0.2°, 31.4 ± 0.2°, 31.9 ± 0.2°, 32.6 ± 0.2°, 33.3 ±
0.2°, 33.8 ± 0.2°, 34.8 ± 0.2°, 35.5 ± 0.2°, 36 ± 0.2°, 36.4 ± 0.2°, 37.2 ± 0.2°, 38.1 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 40.8 ± 0.2°, 41.7 ± 0.2°, 42.6 ± 0.2°, 43.2 ± 0.2°, 43.8 ± 0.2°, 44.5 ± 0.2°, 45.8 ± 0.2°, and 48 ± 0.2°.
[0071] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 9.2 ± 0.2°, 10 ± 0.2°, 11.6 ± 0.2°, 12 ± 0.2°, 14 ± 0.2°, 15.9 ± 0.2°, 16.2 ± 0.2°, 16.7 ± 0.2°,
17.4 ± 0.2°, 18.5 ± 0.2°, 18.9 ± 0.2°, 19.9 ± 0.2°, 20.1 ± 0.2°, 20.5 ± 0.2°, 21.2 ± 0.2°, 21.7 ± 0.2°, 23.2 ± 0.2°, 23.6 ± 0.2°, 24.5 ± 0.2°, 25.5 ± 0.2°, 26.2 ± 0.2°, 27.1 ± 0.2°, 28.2 ± 0.2°, 28.6 ± 0.2°, 29.7 ± 0.2°,
30.5 ± 0.2°, 32.2 ± 0.2°, 32.7 ± 0.2°, 33.9 ± 0.2°, 35.1 ± 0.2°, 35.9 ± 0.2°, 37.3 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 43.3 ± 0.2°, 46.5 ± 0.2°, and 47.6 ± 0.2°.
[0072] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 6.2 ± 0.2°, 9.3 ± 0.2°, 10 ± 0.2°, 10.6 ± 0.2°, 11.8 ± 0.2°, 12.2 ± 0.2°, 12.4 ± 0.2°, 14.4 ± 0.2°, 15.1 ± 0.2°, 17 ± 0.2°, 18.7 ± 0.2°, 19 ± 0.2°, 19.3 ± 0.2°, 20.1 ± 0.2°, 20.6 ± 0.2°, 20.9 ± 0.2°, 21.3
± 0.2°, 21.7 ± 0.2°, 22.2 ± 0.2°, 22.7 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 24.4 ± 0.2°, 25.2 ± 0.2°, 26 ± 0.2°, l.l. ± 0.2°, 27.6 ± 0.2°, 28.1 ± 0.2°, 29.6 ± 0.2°, 30.5 ± 0.2°, 31.1 ± 0.2°, 31.5 ± 0.2°, 32.1 ± 0.2°, 33 ±
0.2°, 33.3 ± 0.2°, 34 ± 0.2°, 35.5 ± 0.2°, 37.9 ± 0.2°, 39.1 ± 0.2°, 40.2 ± 0.2°, 41 ± 0.2°, 42.2 ± 0.2°, 43.4
± 0.2°, 44.4 ± 0.2°, 46.4 ± 0.2°, and 48 ± 0.2°.
[0073] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 5.5 ± 0.2°, 7.9 ± 0.2°, 8.1 ± 0.2°, 9.3 ± 0.2°, 10.3 ± 0.2°, 11.3 ± 0.2°, 12.6 ± 0.2°, 13.1 ± 0.2°, 13.6 ± 0.2°, 15 ± 0.2°, 16 ± 0.2°, 16.8 ± 0.2°, 17.6 ± 0.2°, 18.1 ± 0.2°, 18.6 ± 0.2°, 19 ± 0.2°, 20.2 ± 0.2°, 20.7 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°, 22.5 ± 0.2°, 22.7 ± 0.2°, 23.1 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 24.8 ± 0.2°, 25.2 ± 0.2°, 25.5 ± 0.2°, 25.7 ± 0.2°, 26.6 ± 0.2°, 27.3 ± 0.2°, 27.9 ± 0.2°, 28.7 ± 0.2°, 29.6 ± 0.2°, 30.6 ± 0.2°, 31 ± 0.2°, 32.1 ± 0.2°, 33.9 ± 0.2°, 34.7 ± 0.2°, 35.8 ± 0.2°, 36.3 ± 0.2°, 37.7 ± 0.2°, 38.6 ± 0.2°, 40 ± 0.2°, 40.7 ± 0.2°, 42.2 ± 0.2°, 43.4 ± 0.2°, 44.7 ± 0.2°, and 47.4 ± 0.2°.
[0074] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4.2 ± 0.2°, 6.1 ± 0.2°, 7.3 ± 0.2°, 8.4 ± 0.2°, 9.9 ± 0.2°, 11.2 ± 0.2°, 11.6 ± 0.2°, 12.6 ± 0.2°, 13.3 ± 0.2°, 14.6 ± 0.2°, 15.2 ± 0.2°, 15.7 ± 0.2°, 16.3 ± 0.2°, 17.5 ± 0.2°, 18.4 ± 0.2°, 19 ± 0.2°, 19.4 ± 0.2°, 20 ± 0.2°, 20.4 ± 0.2°, 20.7 ± 0.2°, 20.9 ± 0.2°, 21.9 ± 0.2°, 22.5 ± 0.2°, 22.7 ± 0.2°, 23.4 ± 0.2°, 23.8 ± 0.2°, 24.9 ± 0.2°, 25.4 ± 0.2°, 25.8 ± 0.2°, 26.6 ± 0.2°, 27 ± 0.2°, 28.5 ± 0.2°, 29.3 ± 0.2°, 30.4 ± 0.2°,
30.8 ± 0.2°, 32.2 ± 0.2°, 34.4 ± 0.2°, 35.2 ± 0.2°, 36.2 ± 0.2°, 37.1 ± 0.2°, 39.3 ± 0.2°, 40.3 ± 0.2°, 42.5 ± 0.2°, 43.6 ± 0.2°, and 45.4 ± 0.2°.
[0075] In some embodiments, the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 8 selected from the group consisting of: 5.5 ± 0.2°, 7.1 ± 0.2°, 8.2 ± 0.2°, 10.8 ± 0.2°, 11.4 ± 0.2°, 12 ± 0.2°, 12.8 ± 0.2°, 13.3 ± 0.2°,
16.2 ± 0.2°, 16.5 ± 0.2°, 17.2 ± 0.2°, 17.6 ± 0.2°, 17.9 ± 0.2°, 18.4 ± 0.2°, 19.1 ± 0.2°, 19.6 ± 0.2°, 20.9 ± 0.2°, 21.2 ± 0.2°, 21.8 ± 0.2°, 22 ± 0.2°, 22.4 ± 0.2°, 22.6 ± 0.2°, 23.5 ± 0.2°, 24.3 ± 0.2°, 26.2 ± 0.2°, 27 ± 0.2°, Tl.l ± 0.2°, 29.2 ± 0.2°, 30.2 ± 0.2°, 31.1 ± 0.2°, 33.1 ± 0.2°, 33.9 ± 0.2°, 34.8 ± 0.2°, 35.7 ± 0.2°,
38.8 ± 0.2°, 40 ± 0.2°, 42.3 ± 0.2°, and 43.5 ± 0.2°.
2-(Diethylamino)-ethanol salt
[0076] In some embodiments, the salt of the present disclosure is a 2-(diethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate. In some embodiments, the 2-(diethylamino)-ethanol salt of SCO-101 is crystalline.
[0077] In some embodiments, the 2-(diethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 21, 22, or 23.
[0078] In some embodiments, the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5 ± 0.2°, 5.1 ± 0.2°, 9.3 ± 0.2°, 10.6 ± 0.2°, 10.7 ± 0.2°, 12.3 ± 0.2°, 14.3 ± 0.2°,
15.3 ± 0.2°, 15.5 ± 0.2°, 17.9 ± 0.2°, 18.1 ± 0.2°, 18.7 ± 0.2°, 19 ± 0.2°, 19.4 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 24 ± 0.2°, 24.5 ± 0.2°, 24.7 ± 0.2°, 25.2 ± 0.2°, 25.7 ± 0.2°, 26.2 ± 0.2°, 26.5 ± 0.2°, 27.2 ± 0.2°, 28.2 ± 0.2°, 28.9 ± 0.2°, 29.2 ± 0.2°, 29.5 ± 0.2°, 30 ± 0.2°,
30.4 ± 0.2°, 31.1 ± 0.2°, 32.8 ± 0.2°, 33.3 ± 0.2°, 34 ± 0.2°, 35.3 ± 0.2°, 35.8 ± 0.2°, 36.6 ± 0.2°, 37.3 ± 0.2°, 37.7 ± 0.2°, 38.3 ± 0.2°, 39.4 ± 0.2°, 40.3 ± 0.2°, 41.2 ± 0.2°, 42.1 ± 0.2°, 43.5 ± 0.2°, 44.2 ± 0.2°, 46.6 ± 0.2°, 47.9 ± 0.2°, and 49 ± 0.2°.
[0079] In some embodiments, the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 3.3 ± 0.2°, 5.7 ± 0.2°, 5.9 ± 0.2°, 6 ± 0.2°, 6.1 ± 0.2°, 6.9 ± 0.2°, 7.1 ± 0.2°, 7.3 ± 0.2°, 12.1 ± 0.2°, 13.9 ± 0.2°, 14.1 ± 0.2°, 15.3 ± 0.2°, 16.1 ± 0.2°, 16.2 ± 0.2°, 16.6 ± 0.2°, 18.7 ± 0.2°, 19.3 ± 0.2°, 19.7 ± 0.2°, 20.4 ± 0.2°, 20.5 ± 0.2°, 21.5 ± 0.2°, 22.3 ± 0.2°, 22.9 ± 0.2°, 23.5 ± 0.2°, 23.8 ±
0.2°, 23.9 ± 0.2°, 24.1 ± 0.2°, 24.5 ± 0.2°, 24.7 ± 0.2°, 24.9 ± 0.2°, 25.2 ± 0.2°, 26 ± 0.2°, 26.3 ± 0.2°, 27.6 ± 0.2°, 27.8 ± 0.2°, 28 ± 0.2°, 28.5 ± 0.2°, 28.6 ± 0.2°, 29.4 ± 0.2°, 30.2 ± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°,
31.1 ± 0.2°, 32.2 ± 0.2°, 32.7 ± 0.2°, 33.5 ± 0.2°, 35.2 ± 0.2°, 36.4 ± 0.2°, 38 ± 0.2°, 39.4 ± 0.2°, 42.3 ± 0.2°, 43.6 ± 0.2°, 44.9 ± 0.2°, 45.5 ± 0.2°, and 49.5 ± 0.2°.
[0080] In some embodiments, the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 6.5 ± 0.2°, 7.9 ± 0.2°, 8.1 ± 0.2°, 8.3 ± 0.2°, 11.1 ± 0.2°, 12.1 ± 0.2°, 12.6 ± 0.2°,
14.1 ± 0.2°, 14.3 ± 0.2°, 14.5 ± 0.2°, 15.2 ± 0.2°, 16.7 ± 0.2°, 17.7 ± 0.2°, 18 ± 0.2°, 18.3 ± 0.2°, 19.4 ± 0.2°, 19.7 ± 0.2°, 20.1 ± 0.2°, 20.6 ± 0.2°, 21.4 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 23.9 ± 0.2°, 24.2 ± 0.2°, 24.4 ± 0.2°, 24.6 ± 0.2°, 25.2 ± 0.2°, 25.2 ± 0.2°, 25.6 ± 0.2°, 26.1 ± 0.2°, 26.3 ± 0.2°, 27.1 ± 0.2°, 27.3 ± 0.2°, 27.7 ± 0.2°, 28.3 ± 0.2°, 28.8 ± 0.2°, 29.2 ± 0.2°, 30.2 ± 0.2°, 31.1 ± 0.2°, 31.4 ± 0.2°, 32.2 ± 0.2°, 32.5 ± 0.2°, 33.2 ± 0.2°, 33.9 ± 0.2°, 34.2 ± 0.2°, 34.5 ± 0.2°, 35.4 ± 0.2°, 36.5 ± 0.2°, 37.2 ± 0.2°, 37.9 ± 0.2°, 38.3 ± 0.2°, 38.6 ± 0.2°, 39.2 ± 0.2°, 40.1 ± 0.2°, 41 ± 0.2°, 41.8 ± 0.2°, 42.3 ± 0.2°, 43.5 ± 0.2°, 44.1 ± 0.2°, 44.7 ± 0.2°, 46 ± 0.2°, 47 ± 0.2°, 47.6 ± 0.2°, 48.2 ± 0.2°, and 48.6 ± 0.2°.
2-(Dimethylamino)-ethanol salt
[0081] In some embodiments, the salt of the present disclosure is a 2-(dimethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate. In some embodiments, the 2-(dimethylamino)-ethanol salt of SCO-101 is crystalline.
[0082] In some embodiments, the 2-(dimethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 24.
[0083] In some embodiments, the 2-(dimethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ± 0.2°, 11 ± 0.2°, 11.6 ± 0.2°, 14.1 ± 0.2°, 15.1 ± 0.2°, 15.5 ± 0.2°, 17.7 ± 0.2°, 18 ± 0.2°, 18.3 ± 0.2°, 18.8 ± 0.2°, 19.5 ± 0.2°, 19.7 ± 0.2°, 20 ± 0.2°, 20.3 ± 0.2°, 20.4 ± 0.2°, 20.7 ± 0.2°, 21.2 ± 0.2°, 22.2 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.1 ± 0.2°, 23.7 ± 0.2°, 25.4 ± 0.2°, 25.6 ± 0.2°, 26.2 ± 0.2°,
26.7 ± 0.2°, l.l. ± 0.2°, 28.1 ± 0.2°, 28.4 ± 0.2°, 28.8 ± 0.2°, 29.4 ± 0.2°, 29.7 ± 0.2°, 30.4 ± 0.2°, 31.2 ±
0.2°, 31.5 ± 0.2°, 31.8 ± 0.2°, 32.8 ± 0.2°, 33 ± 0.2°, 33.5 ± 0.2°, 34.4 ± 0.2°, 34.7 ± 0.2°, 35.4 ± 0.2°, 35.9 ± 0.2°, 36.5 ± 0.2°, 37.2 ± 0.2°, 37.7 ± 0.2°, 38.2 ± 0.2°, 38.7 ± 0.2°, 39.3 ± 0.2°, 39.9 ± 0.2°, 40.6 ± 0.2°,
41.3 ± 0.2°, 42.2 ± 0.2°, 43.3 ± 0.2°, 45 ± 0.2°, 45.7 ± 0.2°, 46.1 ± 0.2°, 47 ± 0.2°, 48 ± 0.2°, and 48.5 ±
0.2°.
Ethanolamine salt
[0084] In some embodiments, the salt of the present disclosure is an ethanolamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the ethanolamine salt of SCO-101 is crystalline.
[0085] In some embodiments, the ethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 25.
[0086] In some embodiments, the ethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ± 0.2°, 10.6 ± 0.2°, 10.9 ± 0.2°, 11.3 ± 0.2°, 13.3 ± 0.2°, 14.3 ± 0.2°, 14.8 ± 0.2°, 16 ± 0.2°, 17.4 ± 0.2°, 19 ± 0.2°, 19.2 ± 0.2°, 19.7 ± 0.2°, 20.4 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 22 ± 0.2°, 22.2 ± 0.2°, 22.4 ± 0.2°, 23.5 ± 0.2°, 24.1 ± 0.2°, 24.3 ± 0.2°, 24.7 ± 0.2°, 25.7 ± 0.2°, 25.8 ± 0.2°, 26.6 ± 0.2°, 26.8 ± 0.2°, l.l. ± 0.2°, 28.1 ± 0.2°, 28.9 ± 0.2°, 29.2 ± 0.2°, 29.6 ± 0.2°, 30.2 ± 0.2°, 30.9 ± 0.2°, 31.8 ± 0.2°, 32.6 ± 0.2°, 33.1 ± 0.2°, 33.7 ± 0.2°, 34.6 ± 0.2°, 35.6 ± 0.2°, 37.6 ± 0.2°, 38.2 ± 0.2°, 38.8 ± 0.2°,
39.7 ± 0.2°, 40.3 ± 0.2°, 40.7 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 43.8 ± 0.2°, 45.1 ± 0.2°, 47.3 ± 0.2°, and
48.8 ± 0.2°.
2-(Hydroxyethyl)-pyrrolidine salt
[0087] In some embodiments, the salt of the present disclosure is a 2-(hydroxyethyl)-pyrrolidine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is crystalline.
[0088] In some embodiments, the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 26.
[0089] In some embodiments, the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.4 ± 0.2°, 6.5 ± 0.2°, 8.3 ± 0.2°, 8.6 ± 0.2°, 11.2 ± 0.2°, 12.8 ± 0.2°, 14.2 ± 0.2°, 14.4 ± 0.2°, 14.9 ± 0.2°, 15.6 ± 0.2°, 16.6 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.4 ± 0.2°, 19.8 ± 0.2°, 20.1 ± 0.2°, 20.5 ± 0.2°, 20.9 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 22.3 ± 0.2°, 22.6 ± 0.2°, 23.2 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 24.2 ± 0.2°, 24.6 ± 0.2°, 25 ± 0.2°, 25.5 ± 0.2°, 25.8 ± 0.2°, 26.2 ± 0.2°, 27.2 ± 0.2°, 27.6 ± 0.2°, 28.1 ± 0.2°, 28.7 ± 0.2°, 29 ± 0.2°, 29.9 ± 0.2°, 30.4 ± 0.2°, 30.9 ± 0.2°, 31.7 ± 0.2°, 32.2 ± 0.2°,
32.8 ± 0.2°, 33.9 ± 0.2°, 34.4 ± 0.2°, 34.9 ± 0.2°, 35.5 ± 0.2°, 36.3 ± 0.2°, 37.3 ± 0.2°, 38.3 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 40.5 ± 0.2°, 41.5 ± 0.2°, 42.6 ± 0.2°, 43 ± 0.2°, 43.6 ± 0.2°, 44.2 ± 0.2°, 46.1 ± 0.2°, 48 ± 0.2°, 48.8 ± 0.2°, and 49.1 ± 0.2°.
Diethanolamine salt
[0090] In some embodiments, the salt of the present disclosure is a diethanolamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. In some embodiments, the diethanolamine salt of SCO-101 is crystalline.
[0091] In some embodiments, the diethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 27.
[0092] In some embodiments, the diethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 8 ± 0.2°, 10.6 ± 0.2°, 11.2 ± 0.2°, 12 ± 0.2°, 12.6 ± 0.2°, 12.9 ± 0.2°, 13.5 ± 0.2°, 14.9 ± 0.2°, 15.7 ± 0.2°, 16.8 ± 0.2°, 17.8 ± 0.2°, 18.1 ± 0.2°, 18.3 ± 0.2°, 19 ± 0.2°, 19.6 ± 0.2°, 19.9 ± 0.2°, 20.6 ± 0.2°, 21.3 ± 0.2°, 21.9 ± 0.2°, 22.1 ± 0.2°, 22.5 ± 0.2°, 23.2 ± 0.2°, 23.5 ± 0.2°, 24 ± 0.2°, 24.2 ± 0.2°, 24.6 ± 0.2°, 24.9 ± 0.2°, 25.3 ± 0.2°, 25.6 ± 0.2°, 25.9 ± 0.2°, 26.4 ± 0.2°, 27.3 ± 0.2°, 27.5 ± 0.2°, 28.2 ± 0.2°, 28.6 ± 0.2°, 28.8 ± 0.2°, 29.5 ± 0.2°, 29.8 ± 0.2°, 30.8 ± 0.2°, 31.2 ± 0.2°, 32 ± 0.2°, 32.2 ± 0.2°, 32.8 ± 0.2°, 34.1 ± 0.2°, 34.6 ± 0.2°, 35.6 ± 0.2°, 36.3 ± 0.2°, 36.9 ± 0.2°, 37.7 ± 0.2°, 38.5 ± 0.2°, 39 ± 0.2°,
39.9 ± 0.2°, 40.3 ± 0.2°, 41.3 ± 0.2°, 41.8 ± 0.2°, 42.5 ± 0.2°, 43 ± 0.2°, 43.3 ± 0.2°, 44 ± 0.2°, 45.3 ± 0.2°, 46.8 ± 0.2°, 47.2 ± 0.2°, 48.8 ± 0.2°, and 49.4 ± 0.2°.
Ammonium salt
[0093] In some embodiments, the salt of the present disclosure is an ammonium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate. In some embodiments, the ammonium salt of SCO-101 is crystalline.
[0094] In some embodiments, the ammonium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 28.
[0095] In some embodiments, the ammonium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.5 ± 0.2°, 9.3 ± 0.2°, 9.8 ± 0.2°, 10.8 ± 0.2°, 12.3 ± 0.2°, 13.4 ± 0.2°, 14.3 ± 0.2°, 14.6 ± 0.2°, 15.6 ± 0.2°,
16.4 ± 0.2°, 17.1 ± 0.2°, 18.2 ± 0.2°, 18.7 ± 0.2°, 19.1 ± 0.2°, 19.4 ± 0.2°, 19.8 ± 0.2°, 20.5 ± 0.2°, 21.2 ± 0.2°, 22 ± 0.2°, 23 ± 0.2°, 23.5 ± 0.2°, 23.9 ± 0.2°, 24.1 ± 0.2°, 24.8 ± 0.2°, 25.1 ± 0.2°, 25.5 ± 0.2°, 25.9 ± 0.2°, 26.2 ± 0.2°, 1 ± 0.2°, 27.2 ± 0.2°, 27.5 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.2 ± 0.2°, 29.5 ± 0.2°,
30.2 ± 0.2°, 30.5 ± 0.2°, 30.7 ± 0.2°, 31.7 ± 0.2°, 32.2 ± 0.2°, 32.6 ± 0.2°, 33.4 ± 0.2°, 34 ± 0.2°, 35.2 ± 0.2°, 36.1 ± 0.2°, 36.7 ± 0.2°, 37 ± 0.2°, 37.6 ± 0.2°, 38.5 ± 0.2°, 39 ± 0.2°, 39.5 ± 0.2°, 40.3 ± 0.2°, 41 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 42.8 ± 0.2°, 43.3 ± 0.2°, 43.9 ± 0.2°, 44.5 ± 0.2°, 45.3 ± 0.2°, 45.7 ± 0.2°,
46.5 ± 0.2°, 47.1 ± 0.2°, 48.2 ± 0.2°, 48.8 ± 0.2°, and 49.5 ± 0.2°.
Tromethamine salt
[0096] In some embodiments, the salt of the present disclosure is a tromethamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate. In some embodiments, the tromethamine salt of SCO-101 is crystalline.
[0097] In some embodiments, the tromethamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 29 or 30.
[0098] In some embodiments, the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 6.6 ± 0.2°, 7.5 ± 0.2°, 10.8 ± 0.2°, 12 ± 0.2°, 13.6 ± 0.2°, 13.9 ± 0.2°, 14.5 ± 0.2°, 15 ± 0.2°, 15.7 ± 0.2°, 17.2 ± 0.2°, 18 ± 0.2°, 19 ± 0.2°, 19.5 ± 0.2°, 20 ± 0.2°, 20.5 ± 0.2°, 21.2 ± 0.2°, 21.6 ± 0.2°, 22.9 ± 0.2°, 23.2 ± 0.2°, 23.5 ± 0.2°, 24.4 ± 0.2°, 25 ± 0.2°, 26.3 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°,
28.6 ± 0.2°, 29.8 ± 0.2°, 30.8 ± 0.2°, 32 ± 0.2°, 33.4 ± 0.2°, 35.4 ± 0.2°, 39.6 ± 0.2°, 43.4 ± 0.2°, 44.9 ± 0.2°, and 46.2 ± 0.2°.
[0099] In some embodiments, the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 4.4 ± 0.2°, 5.7 ± 0.2°, 6.7 ± 0.2°, 6.9 ± 0.2°, 7.4 ± 0.2°, 8.9 ± 0.2°, 9.2 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 13.4 ± 0.2°, 14.1 ± 0.2°, 14.3 ± 0.2°, 14.7 ± 0.2°, 14.9 ± 0.2°, 15.5 ± 0.2°, 15.9 ± 0.2°,
16.2 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°, 17.9 ± 0.2°, 18.3 ± 0.2°, 19.1 ± 0.2°, 19.6 ± 0.2°, 19.9 ± 0.2°, 20.4 ± 0.2°, 20.6 ± 0.2°, 20.7 ± 0.2°, 21.1 ± 0.2°, 21.6 ± 0.2°, 22.5 ± 0.2°, 23 ± 0.2°, 23.2 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 25.3 ± 0.2°, 26.5 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 27.8 ± 0.2°, 28.2 ± 0.2°, 28.4 ± 0.2°, 29 ± 0.2°, 29.8 ± 0.2°, 30.7 ± 0.2°, 31.3 ± 0.2°, 31.8 ± 0.2°, 32.9 ± 0.2°, 33.7 ± 0.2°, 34.5 ± 0.2°, 35.2 ± 0.2°, 35.5 ± 0.2°, 39.4 ± 0.2°, 40.6 ± 0.2°, 43.2 ± 0.2°, 45.2 ± 0.2°, and 46.6 ± 0.2°.
N-Methyl glucamine salt
[0100] In some embodiments, the salt of the present disclosure is an N-methyl glucamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate. In some embodiments, the N- methyl glucamine salt of SCO-101 is crystalline.
[0101] In some embodiments, the N-methyl glucamine salt of SCO-101 is characterized by XRPD 2- Theta peak maxima essentially as depicted in Figure 31.
[0102] In some embodiments, the N-methyl glucamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.9 ± 0.2°, 6.9 ± 0.2°, 7.6 ± 0.2°, 8.9 ± 0.2°, 9.3 ± 0.2°, 11 ± 0.2°, 11.4 ± 0.2°, 12.2 ± 0.2°, 13.4 ± 0.2°, 14 ± 0.2°, 14.8 ± 0.2°, 15.1 ± 0.2°, 15.7 ± 0.2°, 16.3 ± 0.2°, 16.8 ± 0.2°, 17.7 ± 0.2°, 17.9 ±
0.2°, 18.2 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.5 ± 0.2°, 19.9 ± 0.2°, 20.6 ± 0.2°, 21.4 ± 0.2°, 21.6 ± 0.2°,
22 ± 0.2°, 22.3 ± 0.2°, 22.6 ± 0.2°, 23.1 ± 0.2°, 23.6 ± 0.2°, 24.1 ± 0.2°, 24.4 ± 0.2°, 25.1 ± 0.2°, 25.9 ±
0.2°, 26.6 ± 0.2°, 27.8 ± 0.2°, 28.6 ± 0.2°, 29.6 ± 0.2°, 30.7 ± 0.2°, 31.8 ± 0.2°, 32.4 ± 0.2°, 33.5 ± 0.2°,
34.2 ± 0.2°, 35.2 ± 0.2°, 36.3 ± 0.2°, 37.6 ± 0.2°, 38.9 ± 0.2°, 39.8 ± 0.2°, 42.3 ± 0.2°, 43.4 ± 0.2°, 44.8 ± 0.2°, and 48 ± 0.2°.
Process for preparing salts
[0103] The salts of SCO-101 as described herein can be prepared for example as described in Example 1. In some embodiments, a process is provided for preparing a salt comprising a compound of formula (SCO-101),
(SCO-101), or a solvate thereof, and a counterion; wherein the process comprises the steps of: a. Providing a solution or suspension of the compound, b. Mixing the solution or suspension of the compound with a base to obtain the salt, c. Isolating the salt.
[0104] In some embodiments, the solution or suspension is in one or more of: 2-propanol, acetone,
ethanol, ethyl acetate, tetrahydrofurane, and/or acetonitrile.
[0105] In some embodiments, the base is selected from the group consisting of: potassium hydroxide, sodium hydroxide, zinc methoxide, zinc ethoxide, arginine, calcium hydroxide, magnesium hydroxide, choline hydroxide, diethylamine, lysine, ethylenediamine, N,N'-dibenzylethylenediamine (benzathine), piperazine, 2-(diethylamino)-ethanol, 2-(dimethylamino)-ethanol (deanol), ethanolamine (olamine), 2-(hydroxyethyl)-pyrrolidine (epolamine), diethanolamine (diolamine), ammonium hydroxide, tromethamine, and N-methyl glucamine (meglumine).
[0106] In some embodiments, the salt is dried prior to or after isolation, optionally wherein the salt is dried under vacuum.
[0107] In some embodiments, the salt is dried at from 25 °C to 80 °C, such as at 40°C prior to or after isolation, optionally wherein the salt is dried under vacuum.
Pharmaceutical composition
[0108] In some embodiments, a pharmaceutical composition is provided comprising a salt of SCO- 101 as defined herein; and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents.
Salts for treatment of cancer
[0109] In some embodiments, a salt of SCO-101 as defined herein is provided for use in the treatment of cancer. In particular, a method is provided for treatment of cancer comprising administering a salt of SCO-101 as defined herein to a patient having a cancer.
[0110] In some embodiments, the treatment further comprises administering one or more anticancer agents to a patient having cancer.
[0111] In some embodiments, the salt of SCO-101 is administered to the patient daily.
Anti-cancer agents
[0112] In some embodiments, the one or more anti-cancer agents are selected from the group consisting of topoisomerase inhibitors, anti-hormone agents, alkylating agents, mitotic inhibitors, antimetabolites, anti-tumor antibiotics, corticosteroids, targeted anti-cancer therapy, differentiating
agents and immunotherapy.
[0113] In some embodiments, the anti-cancer agent is administered in combination with one or more further anti-cancer agents.
Topoisomerase inhibitors
[0114] In one embodiment, the anti-cancer agent is a topoisomerase I inhibitor or topoisomerase II inhibitor.
[0115] In one embodiment, the anti-cancer agent is a topoisomerase I inhibitor selected from the group consisting of: irinotecan, its active metabolite SN-38, and topotecan.
Anti-hormone agents
[0116] In one embodiment, anti-cancer agent is an anti-hormone agent which is: a. an anti-estrogen selected from the group consisting of: fulvestrant, tamoxifen, toremifene, and clomifene, or b. an anti-progestogen selected from the group consisting of: mifepristone, ulipristal acetate, aglepristone, lilopristone and onapristone.
[0117] In one embodiment, the anti-estrogen is fulvestrant or tamoxifen. In one embodiment, the anti-progestogen is onapristone.
Alkylating agents
[0118] In one embodiment, the anti-cancer agent is an alkylating agent which is: a. a nitrogen mustard selected from the group consisting of: mechlorethamine, chlorambucil, cyclophosphamide, ifosfamide, and melphalan, b. a nitrosourea selected from the group consisting of: streptozocin, carmustine, and lomustine, c. an alkyl sulfonate which is busulfan, d. a triazine selected from the group consisting of: dacarbazine (DTIC) and temozolomide, or e. an ethylenimine selected from the group consisting of: thiotepa and altretamine
(hexamethylmelamine).
[0119] In one embodiment, the alkylating agent is temozolomide.
Antimetabolites
[0120] In one embodiment, the anti-cancer agent is an antimetabolite selected from the group consisting of: 5-fluorouracil, 6-mercaptopurine, Capecitabine, Cytarabine, Floxuridine, Fludarabine, Gemcitabine, Hydroxyurea, Methotrexate, and Pemetrexed.
[0121] In one embodiment, the antimetabolite is 5-fluorouracil or gemcitabine.
Mitotic inhibitors
[0122] In one embodiment, the anti-cancer agent is a mitotic inhibitor which is: a. a taxane selected from the group consisting of: paclitaxel and docetaxel; b. ixabepilone; c. a vinca alkaloid selected from the group consisting of: vinblastine, vincristine, and vinorelbine; or d. estramustine.
[0123] In one embodiment, the mitotic inhibitor is paclitaxel or docetaxel.
Further anti-cancer agents
[0124] In one embodiment, the anti-cancer agent is administered in combination with one or more further anti-cancer agents.
[0125] In one embodiment, the anti-cancer agent is administered in combination with a further anticancer agent which is 5-fluorouracil. In one embodiment, the anti-cancer agent is administered in combination with 5-fluorouracil and folinic acid. In one embodiment, the anti-cancer agent is irinotecan and administered in combination with 5-fluorouracil and folinic acid.
Immunotherapy
[0126] In one embodiment the anti-cancer agent is an immunotherapy agent. Immunotherapy drugs are given to people with cancer to help their immune systems recognize and attack cancer cells.
[0127] There are different types of immunotherapy. Active immunotherapies stimulate the body's own immune system to fight the disease. Passive immunotherapies do not rely on the body to attack the disease; they're immune system components (such as antibodies) created outside the body and given to fight the cancer.
[0128] Examples of active immunotherapies include:
• Monoclonal antibody therapy, such as rituximab (Rituxan®) and alemtuzumab
(Campath®)
• Non-specific immunotherapies and adjuvants (other substances or cells that boost the immune response), such as BCG, interleukin-2 (IL-2), and interferon-alfa
• Immunomodulating drugs, such as thalidomide and lenalidomide (Revlimid®)
[0129] In one embodiment the anti-cancer agent is a PD-1 or PD-L1 inhibitor, such as an antibody capable of inhibiting PD-1 or PD-L1.
[0130] Cancer vaccines are a type of active specific immunotherapy. In one embodiment, the anticancer agent is a cancer vaccine.
Cancers
[0131] In one embodiment, the cancer is a solid tumour or a leukemia. In some embodiments, the cancer is a solid tumour, such as a solid tumour selected from sarcoma, carcinoma and lymphoma.
[0132] In some embodiments, the cancer is selected from the group consisting of colorectal cancer, breast cancer, lung cancer (non small cell lung cancer and small cell lung cancer), one or more glioblastomas, one or more Head and neck cancers, one or more malignant melanomas, basal cell skin cancer, squamous cell skin cancer, liver cancer, pancreatic cancer, prostate cancer, anal cancer, cervix uteri cancer, bladder cancer, corpus uteri cancer, ovarian cancer, gall bladder cancer, one or more sarcomas, one or more leukemias (myeloid and lymphatic), one or more lymphomas, myelomatosis, cholangiocarcinoma, gastric cancer, testicular cancer, uveal cancer, mesothelioma, merkel cell carcinoma, and one or more myelodysplastic syndromes (MDS).
[0133] In some embodiments, the cancer is metastatic cancer.
[0134] In some embodiments, the cancer is colorectal cancer, such as metastatic colorectal cancer.
[0135] In one embodiment, the leukemia is acute myeloid leukemia (AML).
[0136] In some embodiments, the cancer is pancreatic cancer, such as metastatic pancreatic cancer.
[0137] In some embodiments, the cancer is breast cancer, such as metastatic breast cancer.
[0138] In some embodiments, the cancer is a resistant cancer which is resistant to the anti-cancer agent when administered alone.
[0139] In some embodiments, the resistance is de novo resistance. In some embodiments, the resistance is acquired resistance.
Examples
Materials and methods
[0140] Chemicals used in the examples herein, e.g. for buffers and substrates, are commercial products of at least reagent grade.
X-ray Powder Diffraction (XRPD)
[0141] XRPD analysis was carried out on a PANalytical X'pert pro with PIXcel detector (128 channels), scanning the samples between 3 and 50° 20. The material was gently ground to release any agglomerates and loaded onto a multi-well plate with Mylar polymer film to support the sample. The multi-well plate was then placed into the diffractometer and analysed using Cu K radiation (di X = 1.54060 A; ot2 = 1.54443 A; P = 1.39225 A; oti : ot2 ratio = 0.5) running in transmission mode (step size 0.0130° 20, step time 18.87s) using 40 kV / 40 mA generator settings. Data were visualized and images generated using the HighScore Plus 4.7 desktop application (PANalytical, 2017).
Polarised Light Microscopy (PLM)
[0142] The presence of crystallinity (birefringence) was determined using an Olympus BX53 microscope, equipped with cross-polarising lenses and a Motic camera. Images were captured using Motic Images Plus 3.0. All images were recorded using the 20 x objective, unless otherwise stated.
[0143] Thermal events were monitored visually using a calibrated Linkam THM600 hotstage with connected controller unit coupled to an Olympus BX50 polarising microscope equipped with a Motic camera and image capture software (Motic Images Plus 3.0). Approximately 0.5 mg of material was placed onto a microscope coverslip and heated at a rate of 10 °C / min with images taken at routine intervals to document any thermal transitions. All images were recorded using the 10 x objective,
unless otherwise stated.
Thermogravimetric Analysis/ Differential Scanning Calorimetry (TGA/DSC)
[0144] Approximately 5-10 mg of material was added into a pre-tared open aluminium pan and loaded into a TA Instruments Discovery SDT 650 Auto - Simultaneous DSC and held at room temperature. The sample was then heated at a rate of 10 °C/min from 30 °C to 400 °C during which time the change in sample weight was recorded along with the heat flow response (DSC). Nitrogen was used as the sample purge gas, at a flow rate of 200 cm3/min.
Differential Scanning Calorimetry (DSC)
[0145] Approximately 1-5 mg of material was weighed into an aluminium DSC pan and sealed non- hermetically with an aluminium lid. The sample pan was then loaded into a TA Instruments Discovery DSC 2500 differential scanning calorimeter equipped with a RC90 cooler. The sample and reference were heated to 200 °C at a scan rate of 10 °C/min and the resulting heat flow response monitored. The sample was re-cooled to -80 °C and then reheated again to 200 °C all at 10 °C/min. Nitrogen was used as the purge gas, at a flow rate of 50 cm3/min.
Infrared Spectroscopy (IR)
[0146] 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
Nuclear Magnetic Resonance (NMR)
[0147] NMR experiments were performed on a Bruker AVIIIHD spectrometer equipped with a PRODIGY cryoprobe operating at 500.23 MHz for protons or on a Bruker AVIIIHD spectrometer equipped with a DCH cryoprobe operating at 500.12 MHz for protons. Experiments were performed in deuterated dimethyl sulfoxide and each sample was prepared to ca. 10 mM concentration.
Dynamic Vapour Sorption (DVS)
[0148] Approximately 10-20 mg of sample was placed into a mesh vapour sorption balance pan and loaded into a DVS Intrinsic or Advantage dynamic vapour sorption balance by Surface Measurement Systems. The sample was subjected to a ramping profile from 40 - 90% relative humidity (RH) at 10% increments, maintaining the sample at each step until a stable weight had been achieved (dm/dt 0.004%, minimum step length 30 minutes, maximum step length 120 minutes) at 25 °C. After completion of the sorption cycle, the sample was dried using the same procedure to 0% RH and then a second sorption cycle back to 40% RH. Two cycles were performed. The weight change during the sorption/desorption cycles were plotted, allowing for the hygroscopic nature of the sample to be determined. XRPD analysis was then carried out on any solid retained.
Variable Humidity X-ray Powder Diffraction (VH-XRPD)
[0149] VH-XRPD analysis was carried out on a Philips X'Pert Pro Multipurpose diffractometer equipped with a temperature chamber. The samples were scanned between 4 and 34.99 °20 using Cu K radiation (di X = 1.54060 A; ot2 = 1.54443 A; = 1.39225 A; di : a2 ratio = 0.5) running in Bragg- Brentano geometry (step size 0.008 °20) using 40 kV / 40 mA generator settings. Measurements were performed at selected temperatures.
Karl Fischer Titration (KF)
[0150] Approximately 15 mg of solid was weighed into a 10 mL glass vial and tightly sealed with a screw cap. Samples were analysed in duplicate using an InMotion KFOven Autosampler at 150 °C and an average moisture content reported.
High Performance Liquid Chromatography-Ultraviolet Detection (HPLC-UV)
[0151] Column: Waters Cortec UPLC T3, 150 x 3.0 mm, 1.6 pm
Column Temperature: 25 °C
Autosampler Temperature: 2-8 °C
UV wavelength: 254 nm
Injection Volume: l pL
Flow Rate: 0.6 mL/min
Mobile Phase A: 0.075 % TFA in H2O
Mobile Phase B: 0.075 % TFA in acetonitrile
[0152] An automated titrator system with an incorporated UV-Vis spectrometer (SiriusT3TM, Pion Inc.) was used to acquire the spectrometric and/or potentiometric data. All experiments were carried out at a controlled temperature 25.0 ± 0.2 °C. The optical system consisted of a photodiode array detector with a deuterium lamp and a fibre optic dip probe. The titrator module consisted of a temperature controller (by Peltier device with in-situ thermocouple), pH electrode, an overhead stirrer, and motorised dispensers for the automatic delivery of assay titrants and reagents via capillaries. The instrumentation was operated using SiriusT3Control software (V2.0). Data processing and generation of the reported pKa values was carried out using SiriusT3Refine software (V2.0).
High Performance Liquid Chromatography-Charged Aerosol Detection (HPLC-CAD)
[0153] Instrumentation: Dionex Ultimate 3000 with Dionex Corona Ultra CAD
Column: In order: Phenomenex Aeris Peptide XB-C18 100 A, 150 x 4.6 mm, 3.6 pm (as guard column) and Dionex Acclaim Trinity P2, 50 x 2.1 mm, 3 pm
Mobile Phase A: Water
Mobile Phase B: 100 mM ammonium formate pH 3.65
Flow Rate: 0.45 mL/min
Runtime: 23 min
Column Temperature: 30 °C
Injection Volume: 4 pL
Detection CAD
Nebuliser Temperature: 30°C
Filter: Corona
Example 1 - Formation of salts
Method
[0154] First, the thermodynamic form of SCO-101, i.e. SCO-101 form I was prepared as follows: SCO- 101 (50 g, 1.0 eq., 101 mmol) was dissolved in 2-propanol (257 g) in a 1 L reactor. The reaction mixture was heated at 50 °C until a clear solution was obtained. To the solution, water (326 g) was added portion wise over a period of 30 min. After cooling the resulting slurry to 20 °C over a period of 1 h SCO-101 crude was isolated by filtration. The filter cake was washed with a mixture of 2- propanol/water (50/50% w/w, 39 g) before SCO-101 crude was re-dissolved in acetone (154 g) at 10 ± 5 °C. To the solution was then added water (195 g) over a period of 70 to 90 min. The crystallized SCO-101 was isolated and washed with a mixture of acetone/water (45:55% w/w, 180 g). The product, SCO-101 form I was dried in an oven under reduced pressure at 45 °C.
[0155] Salt formation experiments were then carried out on 20 selected bases (Table 1) in six solvents
(Table 2) as follows:
• Stock solutions of SCO-101 Form I were prepared in 2-propanol, acetone, ethanol, ethyl acetate and THF as per Table 2. Slurries were prepared with 30 mg of SCO-101 Form I and 500 pL of acetonitrile. • Slurries of 1.1 mol eq. of the solid bases were prepared in 200 pL of the six selected solvents.
• An aliquot of SCO-101 stock solution or the acetonitrile slurry was added to the corresponding base slurry.
• 1.1 mol eq. of liquid bases were added neat to an aliquot of the SCO-101 stock solutions or
SCO-101 slurry with an additional 200 pL of the corresponding solvent.
Table 2: Selected solvents for salt formation experiments
• A magnetic stirrer bar was added to all experiments and the vials were capped and sealed with parafilm. The experiments were temperature cycled as follows:
• Hold at 40 °C for 1 hour
• Ramp to 5 °C at 0.1 °C/min
• Hold at 5 °C for 1 hour
• Ramp to 40 °C at 0.1 °C/min
• After temperature cycling between 5 °C and 40 °C for ca. 72 hours, observations were noted.
• Any slurries were filtered centrifugally, and the solids analysed by XRPD. The filtered solutions of the first set of experiments were returned to the sample vials and these were evaporated alongside the other clear solutions.
• After evaporating for ca. 48 hours, 7 days, or 2 weeks, observations were noted, and any solids and gums were analysed by XRPD.
• The solids were dried under vacuum at 40 °C for ca. 24 hours and re-analysed by XRPD.
• The solids were then stored at 40 °C/75 % RH for ca. 24 hours to determine if the potential salt hits would deliquesce/crystallize.
Results
[0156] In total, 36 distinguishable patterns were obtained from 118 salt formation experiments. 21 potential salt hits were stable after drying the solids under vacuum and storage at 40 °C/75 %RH, these were characterised by TG/DSC, 1H NMR, FT-IR and PLM analysis as described under "Materials and methods". The following salt hits were observed:
• Potassium salt Pattern 1 (hydrated)
• Sodium salt Pattern 1 (hydrated)
• Zinc salt Pattern 2
• L-Arginine salt Pattern 3 (hydrated, 2 equivalents in NMR)
• Diethylamine salt pattern 1
• L-Lysine salt Pattern 6 (hydrated)
• L-Lysine salt Pattern 7 (hydrated)
• Ethylenediamine salt Pattern 1
• Benzathine salt Pattern 1
• Piperazine salt Patterns 2, 4, 5, 6 and 7 (Pattern 7 was hydrated)
• 2-(Diethylamino)-ethanol salt Pattern 1 and 3 (Pattern 3 was hydrated)
• 2-(Dimethylamino)-ethanol salt Pattern 1
• Ethanolamine salt Pattern 1
• 2-(Hydroxyethyl)-Pyrrolidine salt Pattern 1
• Diethanolamine salt Pattern 1
• Choline salt Pattern 1 (hydrated)
[0157] The summaries of the salt formation experiments can be found in Figures 33-36.
Conclusions
[0158] The present example demonstrates the successful preparation of a range of salts of SCO-101, including crystals and amorphs thereof. The crystals have distinguishable XRPD patterns, and the salts including the crystals, and amorphs thereof are potential candidates for pharmaceutical development.
Example 2 - Physical-chemical evaluation of salts
2.1 - 7-Day Stability Assessment
Method
[0159] A 7-day stability assessment was carried out on SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1. The procedure was as follows:
• 15 mg of the SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1 were stored under the following conditions for 7 days: o 25 °C/60 %RH (open vial, covered with tissue) o 40 °C/75 %RH (open vial, covered with tissue) o 80 °C (closed vial)
• After 7 days, a visual observation of the solids was made, and the solids were analysed by XRPD and HPLC purity.
Results
[0160] The following results were obtained from the 7-day stability assessment:
• No visual changes were observed for either salt at any of the stability conditions after 7 days.
• SCO-101 sodium salt Pattern 2 was stable by XRPD after storage at 25 °C/60 %RH and 40 °C/75 %RH for 7 days, but conversion to Pattern 1 was noted after storage at 80 °C.
• SCO-101 ethylenediamine salt Pattern 1 was stable by XRPD after 7 days at each stability condition.
• No impurities were observed by HPLC before or after the stability testing.
[0161] The 7-day stability assessment found no changes in appearance after 7 days at 25 °C/60 %RH, 40 °C/75 %RH, or 80 °C for either the SCO-101 sodium salt Pattern 2 or SCO-101 ethylenediamine salt Pattern 1 material. HPLC analysis found no impurities and a purity by relative area > 99.99 % was reported. By XRPD, SCO-101 sodium salt Pattern 2 was stable at 25 °C/60 %RH and 40 °C/75 %RH, but converted to Pattern 1 at 80 °C. The solid form of SCO-101 ethylenediamine salt Pattern 1 was stable after 7 days at each stability condition, as confirmed by XRPD.
Conclusions
[0162] The present example demonstrates that the sodium and ethylenediamine salts of SCO-101 are stable at room temperature and 40 °C. Further, the ethylenediamine salt of SCO-101 was shown to be fully stable even at 80 °C. This supports that the ethylenediamine salt and in particular crystals thereof display increased thermal stability.
2.2 Thermodynamic Solubility Determination
Method
[0163] A thermodynamic solubility determination was carried out on SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1 in buffers at pH 1.2, 4.5, and 7.4 as well as in FaSSIF and FeSSIF. The procedure was as follows:
[0164] Slurries were prepared of 10 mg SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1 in 1 mL of the following buffer systems: o 0.1 HCI/KCI buffer at pH 1.2 o 0.1 M acetate buffer at pH 4.5 o 0.1 M phosphate buffer at pH 7.4 o FaSSIF o FeSSIF
[0165] White slurries were observed in all cases where the experiments were prepared at concentration of 10 mg/mL. The initial pH was measured, and adjustments made where necessary. The slurries were then agitated at 37 °C. After 20 hours, the pH was measured, and adjustments made where necessary. The slurries were filtered centrifugally. The solutions were analysed by HPLC for concentration, and the solids by XRPD.
[0166] For comparison, the free acid of SCO-101 crystal form I was also subjected to thermodynamic solubility determination: 100 pL aliquots of both FaSSIF and FeSSIF buffers were added to 10 mg of SCO-101 Form 1 in 2 mL vials until a total of 1 mL was added. The pH of the slurries was measured. The experiments were agitated at 37°C for 24 hrs in an incubator/shaker. After 24 hrs, observations
were made on the FaSSIF and FeSSIF slurries and pH was measured. The slurries were then centrifuged, and the solids were analyzed by XRPD and compared against the received SCO-101. The saturated solutions were then analyzed by HPLC to assess the concentration of SCO-101.
Results
[0167] The following results were obtained from the thermodynamic solubility determination of the experiments on the sodium and ethylenediamine salts of SCO-101:
• HPLC analysis determined the solubility at 37 °C was below 0.002 mg/mL for both salts at pH 1.2 and 4.5 and below 0.001 mg/mL at pH 7.4. The solubility of the sodium salt was determined to be 0.45 mg/mL in FaSSIF and 1.1 mg/mL in FeSSIF (a difference of 0.65 mg/mL).
• The solubility of the ethylenediamine salt was determined to be 0.04 mg/mL in FaSSIF and 1.6 mg/mL in FeSSIF (a difference of 1.56 mg/mL).
[0168] The following results were obtained from the thermodynamic solubility determination of the experiments on the free acid of SCO-101 form I:
• The solubility of SCO-101 Form I in FaSSIF media was 0.1278 mg/mL and in FeSSIF media was higher at 0.7022 mg/mL after 24 hrs at 37 °C (a difference of 0.57 mg/mL). There was no change in Form I.
Conclusions
[0169] The present example demonstrates that the free acid, the sodium salt, and the ethylenediamine salt of SCO-101 display significantly different solubilities. The sodium salt of SCO-101 in particular was shown to be significantly more soluble in FaSSIF, i.e. an assay mimicking a fasting state, compared to both the free form and the ethylenediamine form.
2.3 Salt Disproportionation Study
Method
[0170] A salt disproportionation study was carried out on SCO-101 sodium salt Pattern 2 and ethylenediamine salt Pattern 1 in unbuffered water to determine if the salts were stable under aqueous conditions. The procedure was as follows:
• Slurries were prepared of 10 mg of SCO-101 sodium salt Pattern 2 (batch 1) and ethylenediamine salt Pattern 1 in 0.5 mL of unbuffered water.
• The slurries were stirred at 25 °C for ca. 24 hours.
• Dissolution was noted for the sodium salt Pattern 2 experiment so 50 mg of sodium salt
Pattern 2 (batch 2) was added to obtain a slurry and this was stirred for a further 24 hours.
• The ethylenediamine salt Pattern 1 experiment was a slurry after 24 hours so this was filtered centrifugally (0.22 pm Nylon filter, 2 min, 10000 RPM) and the solid analysed by XRPD.
• After an additional 24 hours of stirring at 25 °C, the sodium salt Pattern 1 experiment was filtered centrifugally and the solid analysed by XRPD.
Results
[0171] The experimental details, observations, and results of the salt disproportionation study were summarised in Table 3.
Notes: +) predominantly amorphous; 1) SCO-101 ethylenediamine Pattern 1
Conclusions
[0172] The salt disproportionation study found that SCO-101 sodium salt Pattern 2 was more soluble in unbuffered water than any previous forms as a clear solution was noted at 20 mg/mL after 24 hours at 25 °C. This demonstrates that the SCO-101 sodium salt and crystals thereof can be useful in formulations where high solubility is desired.
Claims
Claims
(SCO-101), or a solvate thereof, and a counterion.
2. The salt according to any one of the preceding claims, wherein the salt comprises one or more of the compound of formula (SCO-101), and one or more counterions.
3. The salt according to any one of the preceding claims, wherein the counterion is monovalent, divalent, trivalent, or tetravalent, such as monovalent or divalent.
4. The salt according to any one of the preceding claims, wherein the counterion is organic or inorganic.
5. The salt according to any one of the preceding claims, wherein the counterion comprises one or more alkali metals, one or more alkaline earth metals, and/or one or more transition metals.
6. The salt according to any one of the preceding claims, wherein the counterion is selected from the group consisting of: lithium, potassium, sodium, cesium, zinc, aluminum, chloroprocaine, procaine, triethylamine, histidine, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'-dibenzylethylenediamine, piperazine, 2-(diethylamino)- ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
7. The salt according to any one of the preceding claims, wherein the counterion is selected from the group consisting of: potassium, sodium, zinc, arginine, calcium, magnesium, choline, diethylamine, lysine, ethylenediamine, N,N'-dibenzylethylenediamine, piperazine, 2- (diethylamino)-ethanol, 2-(dimethylamino)-ethanol, ethanolamine, 2-(hydroxyethyl)-
pyrrolidine, diethanolamine, ammonia, tromethamine, and N-methyl glucamine.
8. The salt according to any one of the preceding claims, wherein the counterion is selected from the group consisting of: sodium and ethylenediamine.
9. The salt according to any one of the preceding claims, wherein the solvate is of a solvent selected from the group consisting of: water, 2-propanol, acetone, acetonitrile, ethanol, methanol, ethyl acetate, and tetrahydrafurane (THF).
10. The salt according to any one of the preceding claims, wherein the salt is amorphous or crystalline.
11. The salt according to any one of the preceding claims, wherein the salt is anhydrous.
12. The salt according to any one of the preceding claims, wherein the salt is a potassium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, preferably a dihydrate.
13. The salt according to claim 12, wherein the potassium salt of SCO-101 is crystalline.
14. The salt according to claim 13, wherein the potassium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 1.
15. The salt according to claim 13, wherein the potassium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 10.4 ± 0.2°, 10.8 ± 0.2°, 11.9 ± 0.2°, 12.8 ± 0.2°, 13.1 ± 0.2°, 14.1 ± 0.2°, 15.8 ± 0.2°, 17.4 ± 0.2°, 18.2 ± 0.2°, 19.8 ± 0.2°, 20.4 ± 0.2°, 20.9 ± 0.2°, 22.2 ± 0.2°, 22.9 ± 0.2°, 24 ± 0.2°, 24.6 ± 0.2°, 25.7 ± 0.2°, 26.3 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.6 ± 0.2°, 30.1 ± 0.2°, 31.1 ± 0.2°, 31.8 ± 0.2°, 32.6 ± 0.2°, 33.1 ± 0.2°, 34.5 ± 0.2°, 35.5 ± 0.2°, 36.4 ± 0.2°, 37.2 ± 0.2°, 38.4 ± 0.2°, 39.8 ± 0.2°, 42.6 ± 0.2°, 43.4 ± 0.2°, 44.4 ± 0.2°, and 45.2 ± 0.2°.
16. The salt according to any one of claims 1-11, wherein the salt is a sodium salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate.
17. The salt according to claim 16, wherein the sodium salt of SCO-101 is crystalline.
18. The salt according to claim 16, wherein the sodium salt of SCO-101 is amorphous.
19. The salt according to claim 17, wherein the sodium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 2 or 32.
20. The salt according to claim 17, wherein the sodium salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 8.9 ± 0.2°, 10.1 ± 0.2°, 11.2 ± 0.2°, 11.6 ± 0.2°, 13.1 ± 0.2°, 14 ± 0.2°, 14.9 ± 0.2°, 15.8 ± 0.2°, 16.7 ± 0.2°, 17.3 ± 0.2°, 18 ± 0.2°, 18.6 ± 0.2°, 18.7 ± 0.2°, 19.7 ±
0.2°, 20.2 ± 0.2°, 20.8 ± 0.2°, 21.6 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.7 ± 0.2°, 24.7
± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°, 26.8 ± 0.2°, 27.1 ± 0.2°, 27.6 ± 0.2°, 28.2 ± 0.2°, 28.9
± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.3 ± 0.2°, 32 ± 0.2°, 32.7 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 35 ±
0.2°, 35.8 ± 0.2°, 36.8 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.9 ± 0.2°, 41.4 ± 0.2°, 42 ± 0.2°, 42.8 ± 0.2°, 44.5 ± 0.2°, and 46.9 ± 0.2°.
21. The salt according to claim 17, wherein the sodium salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 8.9 ± 0.2°, 10.1 ± 0.2°, 11.2 ± 0.2°, 11.6 ± 0.2°, 13.1 ± 0.2°, 14 ± 0.2°, 14.9 ± 0.2°, 15.8 ± 0.2°, 16.7 ± 0.2°, 17.3 ± 0.2°, 18 ± 0.2°, 18.6 ± 0.2°, 18.7 ± 0.2°, 19.7 ±
0.2°, 20.2 ± 0.2°, 20.8 ± 0.2°, 21.6 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.7 ± 0.2°, 24.7
± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°, 26.8 ± 0.2°, 27.1 ± 0.2°, 27.6 ± 0.2°, 28.2 ± 0.2°, 28.9
± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.3 ± 0.2°, 32 ± 0.2°, 32.7 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 35 ±
0.2°, 35.8 ± 0.2°, 36.8 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.9 ± 0.2°, 41.4 ± 0.2°, 42 ± 0.2°, 42.8 ± 0.2°, 44.5 ± 0.2°, 46.9 ± 0.2°.
22. The salt according to any one of claims 1-11, wherein the salt is a zinc salt of SCO-101, which is optionally an anhydrate.
23. The salt according to claim 22, wherein the zinc salt of SCO-101 is crystalline.
24. The salt according to claim 23, wherein the zinc salt of SCO-101 is characterized by XRPD 2- Theta peak maxima essentially as depicted in Figure 3.
The salt according to claim 23, wherein the zinc salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 4.3 ± 0.2°, 7.3 ± 0.2°, 8.6 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 12.4 ± 0.2°, 13 ± 0.2°,
13.9 ± 0.2°, 15.1 ± 0.2°, 16.2 ± 0.2°, 17.2 ± 0.2°, 18.3 ± 0.2°, 18.9 ± 0.2°, 19.9 ± 0.2°, 20.4 ± 0.2°,
21.2 ± 0.2°, 22.7 ± 0.2°, 23.4 ± 0.2°, 23.9 ± 0.2°, 24.7 ± 0.2°, 26.5 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°,
30.7 ± 0.2°, 31.6 ± 0.2°, 33.4 ± 0.2°, 34.3 ± 0.2°, 36 ± 0.2°, 39.6 ± 0.2°, and 43.4 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is an arginine salt of SCO-101, which is optionally a diarginine salt. The salt according to claim 26, wherein the arginine salt of SCO-101 is crystalline. The salt according to claim 27, wherein the arginine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 4. The salt according to claim 27, wherein the arginine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.5 ± 0.2°, 6.6 ± 0.2°, 7.7 ± 0.2°, 8.5 ± 0.2°, 9.2 ± 0.2°, 9.6 ± 0.2°, 10.4 ± 0.2°, 15 ± 0.2°, 16.7 ± 0.2°, 17.4 ± 0.2°, 17.8 ± 0.2°, 18.7 ± 0.2°, 19.2 ± 0.2°, 19.6 ± 0.2°,
20.3 ± 0.2°, 21.3 ± 0.2°, 21.8 ± 0.2°, 22.2 ± 0.2°, 22.9 ± 0.2°, 23.8 ± 0.2°, 24.9 ± 0.2°, 25.4 ± 0.2°, 26 ± 0.2°, 26.8 ± 0.2°, 28.9 ± 0.2°, 33.9 ± 0.2°, 34.9 ± 0.2°, 36.9 ± 0.2°, 38.4 ± 0.2°, and 41.3 ± 0.2°. The salt according to claim 27, wherein the arginine salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 4.1 ± 0.2°, 6.2 ± 0.2°, 8.2 ± 0.2°, 10.7 ± 0.2°, 11.3 ± 0.2°, 12.8 ± 0.2°, 13.2 ± 0.2°, 14.3 ± 0.2°, 14.8 ± 0.2°, 16.4 ± 0.2°, 17.7 ± 0.2°, 18.2 ± 0.2°, 18.6 ± 0.2°, 19.2
± 0.2°, 19.5 ± 0.2°, 19.9 ± 0.2°, 20.5 ± 0.2°, 21.5 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 23.9 ± 0.2°, 24.5
± 0.2°, 25.3 ± 0.2°, 25.7 ± 0.2°, 26.1 ± 0.2°, 26.4 ± 0.2°, 27.3 ± 0.2°, 28 ± 0.2°, 28.9 ± 0.2°, 29.8
± 0.2°, 31 ± 0.2°, 31.5 ± 0.2°, 32.7 ± 0.2°, 33.2 ± 0.2°, 34.5 ± 0.2°, 35.9 ± 0.2°, 39.2 ± 0.2°, 40.6
± 0.2°, 41.6 ± 0.2°, 43.3 ± 0.2°, and 45.2 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a calcium salt of SCO-101.
The salt according to claim 31, wherein the calcium salt of SCO-101 is crystalline. The salt according to any one of claims 1-11, wherein the salt is a choline salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate. The salt according to claim 33, wherein the choline salt of SCO-101 is crystalline. The salt according to claim 34, wherein the choline salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 5. The salt according to claim 34, wherein the choline salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.2 ± 0.2°, 9.8 ± 0.2°, 10.4 ± 0.2°, 11.7 ± 0.2°, 12.7 ± 0.2°, 13.7 ± 0.2°, 15.7 ± 0.2°, 16.1 ± 0.2°, 16.7 ± 0.2°, 17.6 ± 0.2°, 17.8 ± 0.2°, 18.2 ± 0.2°, 18.9 ± 0.2°, 19.6 ± 0.2°, 20.8
± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 22.2 ± 0.2°, 22.6 ± 0.2°, 22.9 ± 0.2°, 23.1 ± 0.2°, 23.5 ± 0.2°, 23.9
± 0.2°, 24.5 ± 0.2°, 24.8 ± 0.2°, 25.2 ± 0.2°, 25.6 ± 0.2°, 26 ± 0.2°, 26.6 ± 0.2°, 27.1 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31.3 ± 0.2°, 31.7 ± 0.2°, 32.6 ± 0.2°, 33.5 ± 0.2°, 34.2
± 0.2°, 34.7 ± 0.2°, 35.5 ± 0.2°, 36.9 ± 0.2°, 39.6 ± 0.2°, 40.6 ± 0.2°, 41.7 ± 0.2°, 42.6 ± 0.2°, 43.7
± 0.2°, 45.3 ± 0.2°, and 48.2 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a diethylamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate. The salt according to claim 37, wherein the diethylamine salt of SCO-101 is crystalline. The salt according to claim 38, wherein the diethylamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 6. The salt according to claim 38, wherein the diethylamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.8 ± 0.2°, 9.8 ± 0.2°, 10 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 12.3 ± 0.2°, 12.6 ± 0.2°, 13 ± 0.2°, 13.4 ± 0.2°, 15.5 ± 0.2°, 16.3 ± 0.2°, 16.7 ± 0.2°, 17.4 ± 0.2°, 17.6 ± 0.2°, 18 ± 0.2°, 19.6 ± 0.2°, 19.8 ± 0.2°, 20 ± 0.2°, 20.3 ± 0.2°, 21.4 ± 0.2°, 21.6 ± 0.2°, 21.9 ± 0.2°, 22.2 ± 0.2°, 22.6 ± 0.2°, 23 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 24.8 ± 0.2°, 25.4 ± 0.2°, 26 ±
0.2°, 26.3 ± 0.2°, 26.8 ± 0.2°, 27.2 ± 0.2°, 27.4 ± 0.2°, 27.8 ± 0.2°, 28.3 ± 0.2°, 28.7 ± 0.2°, 29.6 ± 0.2°, 30.5 ± 0.2°, 31 ± 0.2°, 32.1 ± 0.2°, 32.6 ± 0.2°, 33 ± 0.2°, 34 ± 0.2°, 34.7 ± 0.2°, 35.6 ± 0.2°, 36 ± 0.2°, 36.5 ± 0.2°, 37.4 ± 0.2°, 38.4 ± 0.2°, 39.1 ± 0.2°, 40.2 ± 0.2°, 40.8 ± 0.2°, 41.8 ± 0.2°, 42.8 ± 0.2°, 43.4 ± 0.2°, 44.1 ± 0.2°, 45.4 ± 0.2°, 46.5 ± 0.2°, 47.6 ± 0.2°, and 48.3 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a L-lysine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as a monohydrate. The salt according to claim 41, wherein the L-lysine salt of SCO-101 is crystalline. The salt according to claim 42, wherein the L-lysine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 7, 8, 9, or 10. The salt according to claim 42, wherein the L-lysine salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 4.4 ± 0.2°, 8.9 ± 0.2°, 9.7 ± 0.2°, 10.7 ± 0.2°, 12.4 ± 0.2°, 13.1 ± 0.2°, 13.4 ± 0.2°, 13.9 ± 0.2°, 14 ± 0.2°, 14.8 ± 0.2°, 15.4 ± 0.2°, 15.6 ± 0.2°, 16.1 ± 0.2°, 17.2 ± 0.2°, 17.8 ± 0.2°, 19.4 ± 0.2°, 20.1 ± 0.2°, 20.5 ± 0.2°, 20.9 ± 0.2°, 21.3 ± 0.2°, 21.9 ± 0.2°, 22.3 ± 0.2°, 22.7 ± 0.2°, 22.9 ± 0.2°, 23.3 ± 0.2°, 23.7 ± 0.2°, 24.2 ± 0.2°, 24.7 ± 0.2°, 25.2 ± 0.2°, 26.1
± 0.2°, 26.4 ± 0.2°, 27.1 ± 0.2°, 27.9 ± 0.2°, 28.3 ± 0.2°, 29.7 ± 0.2°, 30.8 ± 0.2°, 31.2 ± 0.2°, 32.2
± 0.2°, 33.3 ± 0.2°, 34.3 ± 0.2°, 34.9 ± 0.2°, 35.6 ± 0.2°, 36.1 ± 0.2°, 37.1 ± 0.2°, 37.5 ± 0.2°, 38.8
± 0.2°, 39.7 ± 0.2°, 40.3 ± 0.2°, 43.4 ± 0.2°, 45.5 ± 0.2°, 46.6 ± 0.2°, 47.2 ± 0.2°. The salt according to claim 42, wherein the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 4.5 ± 0.2°, 9.7 ± 0.2°, 10.3 ± 0.2°, 11.6 ± 0.2°, 13.8 ± 0.2°, 14.5 ± 0.2°, 14.7 ± 0.2°, 15.2 ± 0.2°, 15.9 ± 0.2°, 17.1 ± 0.2°, 17.7 ± 0.2°, 18.1 ± 0.2°, 18.6 ± 0.2°, 18.9 ± 0.2°, 19.4 ± 0.2°, 19.6 ± 0.2°, 20.9 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 22 ± 0.2°, 22.5 ± 0.2°, 23 ± 0.2°, 23.4 ± 0.2°, 24.3 ± 0.2°, 24.9 ± 0.2°, 26 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 27.8 ± 0.2°, 28.6 ± 0.2°, 29 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31.4 ± 0.2°, 32.9 ± 0.2°, 33.4 ± 0.2°, 33.9 ± 0.2°, 34.5 ± 0.2°, 36.2 ± 0.2°, 37.1 ± 0.2°, 38.6 ± 0.2°, 39.3 ± 0.2°, 41.7 ± 0.2°, 43.4 ± 0.2°, 44.6 ± 0.2°, 46 ± 0.2°, 47.1 ± 0.2°, and 49 ± 0.2°. The salt according to claim 42, wherein the L-lysine salt of SCO-101 when measured using Cu
Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 3.5 ± 0.2°, 10.1 ± 0.2°, 10.3 ± 0.2°, 11 ± 0.2°, 12.2 ± 0.2°, 13.5 ± 0.2°, 14.1 ± 0.2°, 14.3 ± 0.2°, 15.4 ± 0.2°, 15.9 ± 0.2°, 16.5 ± 0.2°, 19 ± 0.2°, 19.6 ± 0.2°, 19.8 ±
0.2°, 20.4 ± 0.2°, 20.9 ± 0.2°, 21.2 ± 0.2°, 22.1 ± 0.2°, 22.7 ± 0.2°, 23.3 ± 0.2°, 23.7 ± 0.2°, 24.4
± 0.2°, 24.9 ± 0.2°, 25.5 ± 0.2°, 27 ± 0.2°, 27.8 ± 0.2°, 28.3 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 31 ±
0.2°, 31.6 ± 0.2°, 32.3 ± 0.2°, 33.2 ± 0.2°, 34.5 ± 0.2°, 36.4 ± 0.2°, 38 ± 0.2°, 38.6 ± 0.2°, 39.1 ±
0.2°, 45.6 ± 0.2°, 46.6 ± 0.2°, and 47.9 ± 0.2°.
47. The salt according to claim 42, wherein the L-lysine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4 ± 0.2°, 4.7 ± 0.2°, 8.1 ± 0.2°, 11.4 ± 0.2°, 12.1 ± 0.2°, 12.6 ± 0.2°, 13 ± 0.2°, 13.4 ± 0.2°, 14.3 ± 0.2°, 14.9 ± 0.2°, 15.7 ± 0.2°, 16.2 ± 0.2°, 17.6 ± 0.2°, 17.9 ± 0.2°, 19 ± 0.2°, 19.8 ± 0.2°, 20.3 ± 0.2°, 20.7 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 21.7 ± 0.2°, 22.1 ± 0.2°,
22.4 ± 0.2°, 22.6 ± 0.2°, 23.2 ± 0.2°, 23.3 ± 0.2°, 23.7 ± 0.2°, 24.2 ± 0.2°, 24.4 ± 0.2°, 24.9 ± 0.2°,
25.4 ± 0.2°, 25.7 ± 0.2°, 26.8 ± 0.2°, 27 ± 0.2°, 1 ± 0.2°, 29.1 ± 0.2°, 29.5 ± 0.2°, 30 ± 0.2°, 30.8 ± 0.2°, 31.4 ± 0.2°, 32.1 ± 0.2°, 33.5 ± 0.2°, 34.5 ± 0.2°, 35.2 ± 0.2°, 35.8 ± 0.2°, 36.6 ± 0.2°, 37 ± 0.2°, 37.6 ± 0.2°, 38 ± 0.2°, 38.6 ± 0.2°, 40.4 ± 0.2°, 41 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 43.8 ± 0.2°, 44.2 ± 0.2°, 45.4 ± 0.2°, 45.9 ± 0.2°, 46.6 ± 0.2°, 47.7 ± 0.2°, and 48.5 ± 0.2°.
48. The salt according to any one of claims 1-11, wherein the salt is an ethylenediamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
49. The salt according to claim 48, wherein the ethylenediamine salt of SCO-101 is crystalline.
50. The salt according to claim 49, wherein the ethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 11.
51. The salt according to claim 49, wherein the ethylenediamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 7.2 ± 0.2°, 9.7 ± 0.2°, 10.6 ± 0.2°, 10.8 ± 0.2°, 11.3 ± 0.2°, 13.3 ± 0.2°, 14.3 ± 0.2°, 14.5 ± 0.2°, 15.7 ± 0.2°, 16.2 ± 0.2°, 17.2 ± 0.2°, 18.2 ± 0.2°, 18.7 ± 0.2°, 19.1 ± 0.2°, 19.8 ± 0.2°, 20.1 ± 0.2°, 21.4 ± 0.2°, 21.9 ± 0.2°, 22.2 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 24.2 ± 0.2°, 24.6 ± 0.2°, 25.6 ± 0.2°, 26.1 ± 0.2°, 26.7 ± 0.2°, 26.7 ± 0.2°, 27.1 ± 0.2°, 27.4 ± 0.2°, 27.9 ± 0.2°, 28.9 ± 0.2°, 29.4 ± 0.2°, 29.8 ± 0.2°, 30 ± 0.2°, 30.4 ± 0.2°, 30.6
± 0.2°, 30.8 ± 0.2°, 32 ± 0.2°, 32.9 ± 0.2°, 33.9 ± 0.2°, 34.2 ± 0.2°, 34.9 ± 0.2°, 35.6 ± 0.2°, 36.8 ± 0.2°, 37.6 ± 0.2°, 38 ± 0.2°, 38.9 ± 0.2°, 39.6 ± 0.2°, 40.3 ± 0.2°, 41.2 ± 0.2°, 41.5 ± 0.2°, 42.6
± 0.2°, 43.1 ± 0.2°, 43.6 ± 0.2°, 44.9 ± 0.2°, 46.1 ± 0.2°, 46.8 ± 0.2°, and 48.7 ± 0.2°.
52. The salt according to any one of claims 1-11, wherein the salt is an N,N'- dibenzylethylenediamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
53. The salt according to claim 52, wherein the N,N'-dibenzylethylenediamine salt of SCO-101 is crystalline.
54. The salt according to claim 53, wherein the N,N'-dibenzylethylenediamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 12.
55. The salt according to claim 53, wherein the N,N'-dibenzylethylenediamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.7 ± 0.2°, 7.1 ± 0.2°, 9.2 ± 0.2°, 10.9 ± 0.2°,
11.2 ± 0.2°, 11.5 ± 0.2°, 12 ± 0.2°, 12.6 ± 0.2°, 13.6 ± 0.2°, 14.3 ± 0.2°, 14.6 ± 0.2°, 15.4 ± 0.2°,
15.7 ± 0.2°, 16.8 ± 0.2°, 17 ± 0.2°, 17.2 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.5 ± 0.2°,
20.3 ± 0.2°, 20.5 ± 0.2°, 21 ± 0.2°, 21.4 ± 0.2°, 21.8 ± 0.2°, 22.4 ± 0.2°, 22.7 ± 0.2°, 22.9 ± 0.2°,
23.5 ± 0.2°, 24.3 ± 0.2°, 24.6 ± 0.2°, 24.9 ± 0.2°, 25.5 ± 0.2°, 26 ± 0.2°, 26.5 ± 0.2°, 27 ± 0.2°,
27.3 ± 0.2°, 27.8 ± 0.2°, 28.7 ± 0.2°, 29.5 ± 0.2°, 30.3 ± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.1 ± 0.2°,
31.6 ± 0.2°, 32.2 ± 0.2°, 32.6 ± 0.2°, 32.9 ± 0.2°, 33.7 ± 0.2°, 34.4 ± 0.2°, 35.8 ± 0.2°, 36.4 ± 0.2°,
37.3 ± 0.2°, 38.2 ± 0.2°, 38.9 ± 0.2°, 39.6 ± 0.2°, 40.1 ± 0.2°, 40.8 ± 0.2°, 41.3 ± 0.2°, 41.7 ± 0.2°,
42.6 ± 0.2°, 43.3 ± 0.2°, 43.9 ± 0.2°, 44.8 ± 0.2°, and 48.3 ± 0.2°.
56. The salt according to any one of claims 1-11, wherein the salt is a piperazine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
57. The salt according to claim 56, wherein the piperazine salt of SCO-101 is crystalline.
58. The salt according to claim 57, wherein the piperazine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 13, 14, 15, 16, 17, 18, 19, or 20.
The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5.4 ± 0.2°, 9.2 ± 0.2°, 9.4 ± 0.2°, 10.2 ± 0.2°, 10.9 ± 0.2°, 11.3 ± 0.2°, 12.4 ± 0.2°, 12.7 ± 0.2°, 13.6 ± 0.2°, 14.1 ± 0.2°, 16.3 ± 0.2°, 16.6 ± 0.2°, 17.3 ± 0.2°,
17.7 ± 0.2°, 18.6 ± 0.2°, 19.3 ± 0.2°, 19.9 ± 0.2°, 20.4 ± 0.2°, 21 ± 0.2°, 21.3 ± 0.2°, 21.6 ± 0.2°,
21.8 ± 0.2°, 22.3 ± 0.2°, 22.7 ± 0.2°, 23.5 ± 0.2°, 24 ± 0.2°, 24.4 ± 0.2°, 24.6 ± 0.2°, 25.5 ± 0.2°,
25.8 ± 0.2°, 26.1 ± 0.2°, 26.7 ± 0.2°, 27.9 ± 0.2°, 28.1 ± 0.2°, 28.8 ± 0.2°, 29.4 ± 0.2°, 29.7 ± 0.2°,
30.2 ± 0.2°, 30.7 ± 0.2°, 31.5 ± 0.2°, 32.1 ± 0.2°, 33.4 ± 0.2°, 33.8 ± 0.2°, 34.5 ± 0.2°, 35 ± 0.2°,
35.8 ± 0.2°, 36.4 ± 0.2°, 37.9 ± 0.2°, 38.4 ± 0.2°, 39.1 ± 0.2°, 39.4 ± 0.2°, 40.1 ± 0.2°, 41.1 ± 0.2°, 41.7 ± 0.2°, 42.7 ± 0.2°, 43.5 ± 0.2°, 44.6 ± 0.2°, 46.6 ± 0.2°, 47.5 ± 0.2°, and 49 ± 0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 6.3 ± 0.2°, 9.3 ± 0.2°, 9.6 ± 0.2°, 10 ± 0.2°, 10.6 ± 0.2°,
11.2 ± 0.2°, 11.8 ± 0.2°, 12 ± 0.2°, 12.2 ± 0.2°, 12.4 ± 0.2°, 13.3 ± 0.2°, 13.7 ± 0.2°, 14.6 ± 0.2°,
15.2 ± 0.2°, 16.2 ± 0.2°, 17 ± 0.2°, 17.7 ± 0.2°, 18.1 ± 0.2°, 18.4 ± 0.2°, 18.6 ± 0.2°, 19.3 ± 0.2°,
19.5 ± 0.2°, 20.1 ± 0.2°, 20.6 ± 0.2°, 20.9 ± 0.2°, 21.3 ± 0.2°, 21.7 ± 0.2°, 22 ± 0.2°, 22.2 ± 0.2°,
22.6 ± 0.2°, 22.9 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.3 ± 0.2°, 25.2 ± 0.2°, 25.9 ± 0.2°, 26.5 ± 0.2°,
27.1 ± 0.2°, 27.5 ± 0.2°, 28.1 ± 0.2°, 29 ± 0.2°, 29.6 ± 0.2°, 30.1 ± 0.2°, 31.1 ± 0.2°, 32 ± 0.2°,
33.2 ± 0.2°, 35.9 ± 0.2°, 36.6 ± 0.2°, 37.1 ± 0.2°, 37.9 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 40.9 ± 0.2°,
42.1 ± 0.2°, 43.4 ± 0.2°, and 47.6 ± 0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 3.3 ± 0.2°, 5.9 ± 0.2°, 9.5 ± 0.2°, 9.9 ± 0.2°, 10.7 ± 0.2°,
11.1 ± 0.2°, 12.3 ± 0.2°, 14.2 ± 0.2°, 14.6 ± 0.2°, 15.3 ± 0.2°, 16.1 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°,
17.9 ± 0.2°, 18.9 ± 0.2°, 19.7 ± 0.2°, 20.1 ± 0.2°, 20.4 ± 0.2°, 21.2 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°,
22.3 ± 0.2°, 22.6 ± 0.2°, 23.6 ± 0.2°, 23.9 ± 0.2°, 24.2 ± 0.2°, 24.7 ± 0.2°, 24.9 ± 0.2°, 25.2 ± 0.2°,
25.9 ± 0.2°, 27.3 ± 0.2°, 27.9 ± 0.2°, 28.6 ± 0.2°, 28.9 ± 0.2°, 29.8 ± 0.2°, 30.2 ± 0.2°, 30.6 ± 0.2°, 31 ± 0.2°, 31.4 ± 0.2°, 31.9 ± 0.2°, 32.6 ± 0.2°, 33.3 ± 0.2°, 33.8 ± 0.2°, 34.8 ± 0.2°, 35.5 ± 0.2°, 36 ± 0.2°, 36.4 ± 0.2°, 37.2 ± 0.2°, 38.1 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 40.8 ± 0.2°, 41.7 ± 0.2°,
42.6 ± 0.2°, 43.2 ± 0.2°, 43.8 ± 0.2°, 44.5 ± 0.2°, 45.8 ± 0.2°, and 48 ± 0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using
Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 9.2 ± 0.2°, 10 ± 0.2°, 11.6 ± 0.2°, 12 ± 0.2°, 14 ± 0.2°,
15.9 ± 0.2°, 16.2 ± 0.2°, 16.7 ± 0.2°, 17.4 ± 0.2°, 18.5 ± 0.2°, 18.9 ± 0.2°, 19.9 ± 0.2°, 20.1 ± 0.2°,
20.5 ± 0.2°, 21.2 ± 0.2°, 21.7 ± 0.2°, 23.2 ± 0.2°, 23.6 ± 0.2°, 24.5 ± 0.2°, 25.5 ± 0.2°, 26.2 ± 0.2°,
27.1 ± 0.2°, 28.2 ± 0.2°, 28.6 ± 0.2°, 29.7 ± 0.2°, 30.5 ± 0.2°, 32.2 ± 0.2°, 32.7 ± 0.2°, 33.9 ± 0.2°,
35.1 ± 0.2°, 35.9 ± 0.2°, 37.3 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 43.3 ± 0.2°, 46.5 ± 0.2°, and 47.6 ±
0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 6.2 ± 0.2°, 9.3 ± 0.2°, 10 ± 0.2°, 10.6 ± 0.2°, 11.8 ± 0.2°,
12.2 ± 0.2°, 12.4 ± 0.2°, 14.4 ± 0.2°, 15.1 ± 0.2°, 17 ± 0.2°, 18.7 ± 0.2°, 19 ± 0.2°, 19.3 ± 0.2°,
20.1 ± 0.2°, 20.6 ± 0.2°, 20.9 ± 0.2°, 21.3 ± 0.2°, 21.7 ± 0.2°, 22.2 ± 0.2°, 22.7 ± 0.2°, 23.5 ± 0.2°,
23.8 ± 0.2°, 24.4 ± 0.2°, 25.2 ± 0.2°, 26 ± 0.2°, 27.2 ± 0.2°, 27.6 ± 0.2°, 28.1 ± 0.2°, 29.6 ± 0.2°,
30.5 ± 0.2°, 31.1 ± 0.2°, 31.5 ± 0.2°, 32.1 ± 0.2°, 33 ± 0.2°, 33.3 ± 0.2°, 34 ± 0.2°, 35.5 ± 0.2°,
37.9 ± 0.2°, 39.1 ± 0.2°, 40.2 ± 0.2°, 41 ± 0.2°, 42.2 ± 0.2°, 43.4 ± 0.2°, 44.4 ± 0.2°, 46.4 ± 0.2°, and 48 ± 0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 6 selected from the group consisting of: 5.5 ± 0.2°, 7.9 ± 0.2°, 8.1 ± 0.2°, 9.3 ± 0.2°, 10.3 ± 0.2°,
11.3 ± 0.2°, 12.6 ± 0.2°, 13.1 ± 0.2°, 13.6 ± 0.2°, 15 ± 0.2°, 16 ± 0.2°, 16.8 ± 0.2°, 17.6 ± 0.2°,
18.1 ± 0.2°, 18.6 ± 0.2°, 19 ± 0.2°, 20.2 ± 0.2°, 20.7 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°,
22.5 ± 0.2°, 22.7 ± 0.2°, 23.1 ± 0.2°, 23.7 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 24.8 ± 0.2°, 25.2 ± 0.2°,
25.5 ± 0.2°, 25.7 ± 0.2°, 26.6 ± 0.2°, 27.3 ± 0.2°, 27.9 ± 0.2°, 28.7 ± 0.2°, 29.6 ± 0.2°, 30.6 ± 0.2°, 31 ± 0.2°, 32.1 ± 0.2°, 33.9 ± 0.2°, 34.7 ± 0.2°, 35.8 ± 0.2°, 36.3 ± 0.2°, 37.7 ± 0.2°, 38.6 ± 0.2°, 40 ± 0.2°, 40.7 ± 0.2°, 42.2 ± 0.2°, 43.4 ± 0.2°, 44.7 ± 0.2°, and 47.4 ± 0.2°. The salt according to claim 57, wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 7 selected from the group consisting of: 4.2 ± 0.2°, 6.1 ± 0.2°, 7.3 ± 0.2°, 8.4 ± 0.2°, 9.9 ± 0.2°,
11.2 ± 0.2°, 11.6 ± 0.2°, 12.6 ± 0.2°, 13.3 ± 0.2°, 14.6 ± 0.2°, 15.2 ± 0.2°, 15.7 ± 0.2°, 16.3 ± 0.2°,
17.5 ± 0.2°, 18.4 ± 0.2°, 19 ± 0.2°, 19.4 ± 0.2°, 20 ± 0.2°, 20.4 ± 0.2°, 20.7 ± 0.2°, 20.9 ± 0.2°,
21.9 ± 0.2°, 22.5 ± 0.2°, 22.7 ± 0.2°, 23.4 ± 0.2°, 23.8 ± 0.2°, 24.9 ± 0.2°, 25.4 ± 0.2°, 25.8 ± 0.2°,
26.6 ± 0.2°, 1 ± 0.2°, 28.5 ± 0.2°, 29.3 ± 0.2°, 30.4 ± 0.2°, 30.8 ± 0.2°, 32.2 ± 0.2°, 34.4 ± 0.2°,
35.2 ± 0.2°, 36.2 ± 0.2°, 37.1 ± 0.2°, 39.3 ± 0.2°, 40.3 ± 0.2°, 42.5 ± 0.2°, 43.6 ± 0.2°, and 45.4 ± 0.2°.
66. The salt according to claim 57 , wherein the piperazine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 8 selected from the group consisting of: 5.5 ± 0.2°, 7.1 ± 0.2°, 8.2 ± 0.2°, 10.8 ± 0.2°, 11.4 ± 0.2°, 12 ± 0.2°, 12.8 ± 0.2°, 13.3 ± 0.2°, 16.2 ± 0.2°, 16.5 ± 0.2°, 17.2 ± 0.2°, 17.6 ± 0.2°, 17.9 ± 0.2°,
18.4 ± 0.2°, 19.1 ± 0.2°, 19.6 ± 0.2°, 20.9 ± 0.2°, 21.2 ± 0.2°, 21.8 ± 0.2°, 22 ± 0.2°, 22.4 ± 0.2°,
22.6 ± 0.2°, 23.5 ± 0.2°, 24.3 ± 0.2°, 26.2 ± 0.2°, 27 ± 0.2°, 1 ± 0.2°, 29.2 ± 0.2°, 30.2 ± 0.2°,
31.1 ± 0.2°, 33.1 ± 0.2°, 33.9 ± 0.2°, 34.8 ± 0.2°, 35.7 ± 0.2°, 38.8 ± 0.2°, 40 ± 0.2°, 42.3 ± 0.2°, and 43.5 ± 0.2°.
67. The salt according to any one of claims 1-11, wherein the salt is a 2-(diethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate.
68. The salt according to claim 67, wherein the 2-(diethylamino)-ethanol salt of SCO-101 is crystalline.
69. The salt according to claim 68, wherein the 2-(diethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 21, 22, or 23.
70. The salt according to claim 68, wherein the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 1 selected from the group consisting of: 5 ± 0.2°, 5.1 ± 0.2°, 9.3 ± 0.2°, 10.6 ± 0.2°,
10.7 ± 0.2°, 12.3 ± 0.2°, 14.3 ± 0.2°, 15.3 ± 0.2°, 15.5 ± 0.2°, 17.9 ± 0.2°, 18.1 ± 0.2°, 18.7 ± 0.2°, 19 ± 0.2°, 19.4 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 21.8 ± 0.2°, 22.3 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°,
24 ± 0.2°, 24.5 ± 0.2°, 24.7 ± 0.2°, 25.2 ± 0.2°, 25.7 ± 0.2°, 26.2 ± 0.2°, 26.5 ± 0.2°, 27.2 ± 0.2°,
28.2 ± 0.2°, 28.9 ± 0.2°, 29.2 ± 0.2°, 29.5 ± 0.2°, 30 ± 0.2°, 30.4 ± 0.2°, 31.1 ± 0.2°, 32.8 ± 0.2°,
33.3 ± 0.2°, 34 ± 0.2°, 35.3 ± 0.2°, 35.8 ± 0.2°, 36.6 ± 0.2°, 37.3 ± 0.2°, 37.7 ± 0.2°, 38.3 ± 0.2°,
39.4 ± 0.2°, 40.3 ± 0.2°, 41.2 ± 0.2°, 42.1 ± 0.2°, 43.5 ± 0.2°, 44.2 ± 0.2°, 46.6 ± 0.2°, 47.9 ± 0.2°, and 49 ± 0.2°.
The salt according to claim 68, wherein the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 2 selected from the group consisting of: 3.3 ± 0.2°, 5.7 ± 0.2°, 5.9 ± 0.2°, 6 ± 0.2°, 6.1 ± 0.2°, 6.9 ± 0.2°, 7.1 ± 0.2°, 7.3 ± 0.2°, 12.1 ± 0.2°, 13.9 ± 0.2°, 14.1 ± 0.2°, 15.3 ± 0.2°, 16.1 ± 0.2°, 16.2 ± 0.2°, 16.6 ± 0.2°, 18.7 ± 0.2°, 19.3 ± 0.2°, 19.7 ± 0.2°, 20.4 ± 0.2°, 20.5 ± 0.2°, 21.5
± 0.2°, 22.3 ± 0.2°, 22.9 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 23.9 ± 0.2°, 24.1 ± 0.2°, 24.5 ± 0.2°, 24.7
± 0.2°, 24.9 ± 0.2°, 25.2 ± 0.2°, 26 ± 0.2°, 26.3 ± 0.2°, 27.6 ± 0.2°, 27.8 ± 0.2°, 28 ± 0.2°, 28.5 ±
0.2°, 28.6 ± 0.2°, 29.4 ± 0.2°, 30.2 ± 0.2°, 30.5 ± 0.2°, 30.9 ± 0.2°, 31.1 ± 0.2°, 32.2 ± 0.2°, 32.7
± 0.2°, 33.5 ± 0.2°, 35.2 ± 0.2°, 36.4 ± 0.2°, 38 ± 0.2°, 39.4 ± 0.2°, 42.3 ± 0.2°, 43.6 ± 0.2°, 44.9
± 0.2°, 45.5 ± 0.2°, and 49.5 ± 0.2°. The salt according to claim 68, wherein the 2-(diethylamino)-ethanol salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 3 selected from the group consisting of: 6.5 ± 0.2°, 7.9 ± 0.2°, 8.1 ± 0.2°, 8.3 ± 0.2°,
11.1 ± 0.2°, 12.1 ± 0.2°, 12.6 ± 0.2°, 14.1 ± 0.2°, 14.3 ± 0.2°, 14.5 ± 0.2°, 15.2 ± 0.2°, 16.7 ± 0.2°,
17.7 ± 0.2°, 18 ± 0.2°, 18.3 ± 0.2°, 19.4 ± 0.2°, 19.7 ± 0.2°, 20.1 ± 0.2°, 20.6 ± 0.2°, 21.4 ± 0.2°, 22.4 ± 0.2°, 23.1 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 23.9 ± 0.2°, 24.2 ± 0.2°, 24.4 ± 0.2°, 24.6 ± 0.2°,
25.2 ± 0.2°, 25.2 ± 0.2°, 25.6 ± 0.2°, 26.1 ± 0.2°, 26.3 ± 0.2°, 27.1 ± 0.2°, 27.3 ± 0.2°, 1 ± 0.2°,
28.3 ± 0.2°, 28.8 ± 0.2°, 29.2 ± 0.2°, 30.2 ± 0.2°, 31.1 ± 0.2°, 31.4 ± 0.2°, 32.2 ± 0.2°, 32.5 ± 0.2°,
33.2 ± 0.2°, 33.9 ± 0.2°, 34.2 ± 0.2°, 34.5 ± 0.2°, 35.4 ± 0.2°, 36.5 ± 0.2°, 37.2 ± 0.2°, 37.9 ± 0.2°,
38.3 ± 0.2°, 38.6 ± 0.2°, 39.2 ± 0.2°, 40.1 ± 0.2°, 41 ± 0.2°, 41.8 ± 0.2°, 42.3 ± 0.2°, 43.5 ± 0.2°, 44.1 ± 0.2°, 44.7 ± 0.2°, 46 ± 0.2°, 47 ± 0.2°, 47.6 ± 0.2°, 48.2 ± 0.2°, and 48.6 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a 2-(dimethylamino)-ethanol salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate or monohydrate. The salt according to claim 73, wherein the 2-(dimethylamino)-ethanol salt of SCO-101 is crystalline. The salt according to claim 74, wherein the 2-(dimethylamino)-ethanol salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 24. The salt according to claim 74, wherein the 2-(dimethylamino)-ethanol salt of SCO-101 when
measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ± 0.2°, 11 ± 0.2°, 11.6 ± 0.2°, 14.1 ± 0.2°, 15.1 ± 0.2°, 15.5 ± 0.2°, 17.7 ± 0.2°, 18 ± 0.2°, 18.3 ± 0.2°, 18.8 ± 0.2°, 19.5 ± 0.2°, 19.7 ± 0.2°, 20 ± 0.2°,
20.3 ± 0.2°, 20.4 ± 0.2°, 20.7 ± 0.2°, 21.2 ± 0.2°, 22.2 ± 0.2°, 22.5 ± 0.2°, 22.8 ± 0.2°, 23.1 ± 0.2°,
23.7 ± 0.2°, 25.4 ± 0.2°, 25.6 ± 0.2°, 26.2 ± 0.2°, 26.7 ± 0.2°, 27.2 ± 0.2°, 28.1 ± 0.2°, 28.4 ± 0.2°,
28.8 ± 0.2°, 29.4 ± 0.2°, 29.7 ± 0.2°, 30.4 ± 0.2°, 31.2 ± 0.2°, 31.5 ± 0.2°, 31.8 ± 0.2°, 32.8 ± 0.2°,
33 ± 0.2°, 33.5 ± 0.2°, 34.4 ± 0.2°, 34.7 ± 0.2°, 35.4 ± 0.2°, 35.9 ± 0.2°, 36.5 ± 0.2°, 37.2 ± 0.2°, 37.7 ± 0.2°, 38.2 ± 0.2°, 38.7 ± 0.2°, 39.3 ± 0.2°, 39.9 ± 0.2°, 40.6 ± 0.2°, 41.3 ± 0.2°, 42.2 ± 0.2°,
43.3 ± 0.2°, 45 ± 0.2°, 45.7 ± 0.2°, 46.1 ± 0.2°, 47 ± 0.2°, 48 ± 0.2°, and 48.5 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is an ethanolamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. The salt according to claim 77, wherein the ethanolamine salt of SCO-101 is crystalline. The salt according to claim 78, wherein the ethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 25. The salt according to claim 78, wherein the ethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 9.7 ± 0.2°, 10.6 ± 0.2°, 10.9 ± 0.2°, 11.3 ± 0.2°, 13.3 ± 0.2°, 14.3 ± 0.2°, 14.8 ± 0.2°, 16 ± 0.2°, 17.4 ± 0.2°, 19 ± 0.2°, 19.2 ± 0.2°, 19.7 ± 0.2°, 20.4 ± 0.2°, 21.3 ± 0.2°, 21.5 ± 0.2°, 22 ± 0.2°, 22.2 ± 0.2°, 22.4 ± 0.2°, 23.5 ± 0.2°, 24.1 ± 0.2°, 24.3 ± 0.2°, 24.7 ± 0.2°, 25.7 ± 0.2°, 25.8 ± 0.2°, 26.6 ± 0.2°, 26.8 ± 0.2°, 27.2 ± 0.2°, 28.1 ± 0.2°, 28.9 ± 0.2°, 29.2 ± 0.2°, 29.6 ± 0.2°, 30.2 ± 0.2°, 30.9 ± 0.2°, 31.8 ± 0.2°, 32.6 ± 0.2°, 33.1 ± 0.2°, 33.7 ± 0.2°, 34.6 ± 0.2°, 35.6 ± 0.2°, 37.6 ± 0.2°, 38.2 ± 0.2°, 38.8 ± 0.2°, 39.7 ± 0.2°, 40.3 ± 0.2°, 40.7 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 43.8 ± 0.2°, 45.1 ± 0.2°, 47.3 ± 0.2°, and 48.8 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a 2-(hydroxyethyl)-pyrrolidine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate. The salt according to claim 81, wherein the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is crystalline.
83. The salt according to claim 82, wherein the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 26.
84. The salt according to claim 82, wherein the 2-(hydroxyethyl)-pyrrolidine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 3.4 ± 0.2°, 6.5 ± 0.2°, 8.3 ± 0.2°, 8.6 ± 0.2°, 11.2 ± 0.2°,
12.8 ± 0.2°, 14.2 ± 0.2°, 14.4 ± 0.2°, 14.9 ± 0.2°, 15.6 ± 0.2°, 16.6 ± 0.2°, 17.7 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.4 ± 0.2°, 19.8 ± 0.2°, 20.1 ± 0.2°, 20.5 ± 0.2°, 20.9 ± 0.2°, 21.1 ± 0.2°, 21.5 ± 0.2°, 22.3 ± 0.2°, 22.6 ± 0.2°, 23.2 ± 0.2°, 23.5 ± 0.2°, 23.8 ± 0.2°, 24.2 ± 0.2°, 24.6 ± 0.2°, 25 ± 0.2°,
25.5 ± 0.2°, 25.8 ± 0.2°, 26.2 ± 0.2°, 27.2 ± 0.2°, 27.6 ± 0.2°, 28.1 ± 0.2°, 28.7 ± 0.2°, 29 ± 0.2°,
29.9 ± 0.2°, 30.4 ± 0.2°, 30.9 ± 0.2°, 31.7 ± 0.2°, 32.2 ± 0.2°, 32.8 ± 0.2°, 33.9 ± 0.2°, 34.4 ± 0.2°,
34.9 ± 0.2°, 35.5 ± 0.2°, 36.3 ± 0.2°, 37.3 ± 0.2°, 38.3 ± 0.2°, 39.1 ± 0.2°, 40.1 ± 0.2°, 40.5 ± 0.2°,
41.5 ± 0.2°, 42.6 ± 0.2°, 43 ± 0.2°, 43.6 ± 0.2°, 44.2 ± 0.2°, 46.1 ± 0.2°, 48 ± 0.2°, 48.8 ± 0.2°, and 49.1 ± 0.2°.
85. The salt according to any one of claims 1-11, wherein the salt is a diethanolamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate, such as an anhydrate.
86. The salt according to claim 85, wherein the diethanolamine salt of SCO-101 is crystalline.
87. The salt according to claim 86, wherein the diethanolamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 27.
88. The salt according to claim 86, wherein the diethanolamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 8 ± 0.2°, 10.6 ± 0.2°, 11.2 ± 0.2°, 12 ± 0.2°, 12.6 ± 0.2°, 12.9 ± 0.2°, 13.5 ± 0.2°, 14.9 ± 0.2°, 15.7 ± 0.2°, 16.8 ± 0.2°, 17.8 ± 0.2°, 18.1 ± 0.2°, 18.3 ± 0.2°, 19 ±
0.2°, 19.6 ± 0.2°, 19.9 ± 0.2°, 20.6 ± 0.2°, 21.3 ± 0.2°, 21.9 ± 0.2°, 22.1 ± 0.2°, 22.5 ± 0.2°, 23.2
± 0.2°, 23.5 ± 0.2°, 24 ± 0.2°, 24.2 ± 0.2°, 24.6 ± 0.2°, 24.9 ± 0.2°, 25.3 ± 0.2°, 25.6 ± 0.2°, 25.9
± 0.2°, 26.4 ± 0.2°, 27.3 ± 0.2°, 27.5 ± 0.2°, 28.2 ± 0.2°, 28.6 ± 0.2°, 28.8 ± 0.2°, 29.5 ± 0.2°, 29.8 ± 0.2°, 30.8 ± 0.2°, 31.2 ± 0.2°, 32 ± 0.2°, 32.2 ± 0.2°, 32.8 ± 0.2°, 34.1 ± 0.2°, 34.6 ± 0.2°, 35.6
± 0.2°, 36.3 ± 0.2°, 36.9 ± 0.2°, 37.7 ± 0.2°, 38.5 ± 0.2°, 39 ± 0.2°, 39.9 ± 0.2°, 40.3 ± 0.2°, 41.3
± 0.2°, 41.8 ± 0.2°, 42.5 ± 0.2°, 43 ± 0.2°, 43.3 ± 0.2°, 44 ± 0.2°, 45.3 ± 0.2°, 46.8 ± 0.2°, 47.2 ±
0.2°, 48.8 ± 0.2°, and 49.4 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is an ammonium salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate. The salt according to claim 89, wherein the ammonium salt of SCO-101 is crystalline. The salt according to claim 90, wherein the ammonium salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 28. The salt according to claim 90, wherein the ammonium salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.5 ± 0.2°, 9.3 ± 0.2°, 9.8 ± 0.2°, 10.8 ± 0.2°, 12.3 ± 0.2°, 13.4 ± 0.2°, 14.3 ± 0.2°, 14.6 ± 0.2°, 15.6 ± 0.2°, 16.4 ± 0.2°, 17.1 ± 0.2°, 18.2 ± 0.2°, 18.7 ± 0.2°, 19.1 ± 0.2°, 19.4 ± 0.2°, 19.8 ± 0.2°, 20.5 ± 0.2°, 21.2 ± 0.2°, 22 ± 0.2°, 23 ± 0.2°, 23.5 ± 0.2°, 23.9 ± 0.2°, 24.1 ± 0.2°, 24.8 ± 0.2°, 25.1 ± 0.2°, 25.5 ± 0.2°, 25.9 ± 0.2°, 26.2 ± 0.2°, 27 ± 0.2°, 27.2 ± 0.2°, 27.5 ± 0.2°, 27.9 ± 0.2°, 28.8 ± 0.2°, 29.2 ± 0.2°, 29.5 ± 0.2°, 30.2 ± 0.2°, 30.5 ± 0.2°, 30.7 ± 0.2°, 31.7 ± 0.2°, 32.2 ± 0.2°, 32.6 ± 0.2°, 33.4 ± 0.2°, 34 ± 0.2°, 35.2 ± 0.2°, 36.1 ± 0.2°, 36.7 ± 0.2°, 37 ± 0.2°, 37.6 ± 0.2°, 38.5 ± 0.2°, 39 ± 0.2°, 39.5 ± 0.2°, 40.3 ± 0.2°, 41 ± 0.2°, 41.4 ± 0.2°, 42.3 ± 0.2°, 42.8 ± 0.2°, 43.3 ± 0.2°, 43.9 ± 0.2°, 44.5 ± 0.2°, 45.3 ± 0.2°, 45.7 ± 0.2°, 46.5 ± 0.2°, 47.1 ± 0.2°, 48.2 ± 0.2°, 48.8 ± 0.2°, and 49.5 ± 0.2°. The salt according to any one of claims 1-11, wherein the salt is a tromethamine salt of SCO- 101, which is optionally an anhydrate, monohydrate, or dihydrate. The salt according to claim 93, wherein the tromethamine salt of SCO-101 is crystalline. The salt according to claim 94, wherein the tromethamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 29 or 30. The salt according to claim 94, wherein the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 4 selected from the group consisting of: 6.6 ± 0.2°, 7.5 ± 0.2°, 10.8 ± 0.2°, 12 ± 0.2°, 13.6 ± 0.2°, 13.9 ± 0.2°, 14.5 ± 0.2°, 15 ± 0.2°, 15.7 ± 0.2°, 17.2 ± 0.2°, 18 ± 0.2°, 19 ± 0.2°, 19.5 ± 0.2°, 20 ±
0.2°, 20.5 ± 0.2°, 21.2 ± 0.2°, 21.6 ± 0.2°, 22.9 ± 0.2°, 23.2 ± 0.2°, 23.5 ± 0.2°, 24.4 ± 0.2°, 25 ± 0.2°, 26.3 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 28.6 ± 0.2°, 29.8 ± 0.2°, 30.8 ± 0.2°, 32 ± 0.2°, 33.4 ± 0.2°, 35.4 ± 0.2°, 39.6 ± 0.2°, 43.4 ± 0.2°, 44.9 ± 0.2°, and 46.2 ± 0.2°.
97. The salt according to claim 94, wherein the tromethamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima in pattern 5 selected from the group consisting of: 4.4 ± 0.2°, 5.7 ± 0.2°, 6.7 ± 0.2°, 6.9 ± 0.2°, 7.4 ± 0.2°,
8.9 ± 0.2°, 9.2 ± 0.2°, 11.4 ± 0.2°, 11.9 ± 0.2°, 13.4 ± 0.2°, 14.1 ± 0.2°, 14.3 ± 0.2°, 14.7 ± 0.2°,
14.9 ± 0.2°, 15.5 ± 0.2°, 15.9 ± 0.2°, 16.2 ± 0.2°, 16.7 ± 0.2°, 17.2 ± 0.2°, 17.9 ± 0.2°, 18.3 ± 0.2°,
19.1 ± 0.2°, 19.6 ± 0.2°, 19.9 ± 0.2°, 20.4 ± 0.2°, 20.6 ± 0.2°, 20.7 ± 0.2°, 21.1 ± 0.2°, 21.6 ± 0.2°, 22.5 ± 0.2°, 23 ± 0.2°, 23.2 ± 0.2°, 23.9 ± 0.2°, 24.4 ± 0.2°, 25.3 ± 0.2°, 26.5 ± 0.2°, 26.9 ± 0.2°, 27.4 ± 0.2°, 27.8 ± 0.2°, 28.2 ± 0.2°, 28.4 ± 0.2°, 29 ± 0.2°, 29.8 ± 0.2°, 30.7 ± 0.2°, 31.3 ± 0.2°, 31.8 ± 0.2°, 32.9 ± 0.2°, 33.7 ± 0.2°, 34.5 ± 0.2°, 35.2 ± 0.2°, 35.5 ± 0.2°, 39.4 ± 0.2°, 40.6 ± 0.2°,
43.2 ± 0.2°, 45.2 ± 0.2°, and 46.6 ± 0.2°.
98. The salt according to any one of claims 1-11, wherein the salt is an N-methyl glucamine salt of SCO-101, which is optionally an anhydrate, monohydrate, or dihydrate.
99. The salt according to claim 98, wherein the N-methyl glucamine salt of SCO-101 is crystalline.
100. The salt according to claim 99, wherein the N-methyl glucamine salt of SCO-101 is characterized by XRPD 2-Theta peak maxima essentially as depicted in Figure 31.
101. The salt according to claim 99, wherein the N-methyl glucamine salt of SCO-101 when measured using Cu Ka radiation is characterized by one or more XRPD 2-Theta peak maxima selected from the group consisting of: 5.9 ± 0.2°, 6.9 ± 0.2°, 7.6 ± 0.2°, 8.9 ± 0.2°, 9.3 ± 0.2°, 11 ± 0.2°, 11.4 ± 0.2°, 12.2 ± 0.2°, 13.4 ± 0.2°, 14 ± 0.2°, 14.8 ± 0.2°, 15.1 ± 0.2°, 15.7 ± 0.2°, 16.3 ± 0.2°, 16.8 ± 0.2°, 17.7 ± 0.2°, 17.9 ± 0.2°, 18.2 ± 0.2°, 18.4 ± 0.2°, 18.7 ± 0.2°, 19.5 ± 0.2°, 19.9 ± 0.2°, 20.6 ± 0.2°, 21.4 ± 0.2°, 21.6 ± 0.2°, 22 ± 0.2°, 22.3 ± 0.2°, 22.6 ± 0.2°, 23.1 ± 0.2°, 23.6 ± 0.2°, 24.1 ± 0.2°, 24.4 ± 0.2°, 25.1 ± 0.2°, 25.9 ± 0.2°, 26.6 ± 0.2°, 27.8 ± 0.2°, 28.6 ± 0.2°, 29.6 ± 0.2°, 30.7 ± 0.2°, 31.8 ± 0.2°, 32.4 ± 0.2°, 33.5 ± 0.2°, 34.2 ± 0.2°, 35.2 ± 0.2°, 36.3 ± 0.2°, 37.6 ± 0.2°, 38.9 ± 0.2°, 39.8 ± 0.2°, 42.3 ± 0.2°, 43.4 ± 0.2°, 44.8 ± 0.2°, and 48 ± 0.2°.
(SCO-101), or a solvate thereof, and a counterion; wherein the process comprises the steps of: a. Providing a solution or suspension of the compound, b. Mixing the solution or suspension of the compound with a base to obtain the salt, c. Isolating the salt.
103. The process according to claim 102, wherein the solution or suspension is in one or more of:
2-propanol, acetone, ethanol, ethyl acetate, tetrahydrofurane, and/or acetonitrile.
104. The process according to any one of claims 102-103, wherein the base is selected from the group consisting of: potassium hydroxide, sodium hydroxide, zinc methoxide, zinc ethoxide, arginine, calcium hydroxide, magnesium hydroxide, choline hydroxide, diethylamine, lysine, ethylenediamine, N,N'-dibenzylethylenediamine (benzathine), piperazine, 2-(diethylamino)- ethanol, 2-(dimethylamino)-ethanol (deanol), ethanolamine (olamine), 2-(hydroxyethyl)- pyrrolidine (epolamine), diethanolamine (diolamine), ammonium hydroxide, tromethamine, and N-methyl glucamine (meglumine).
105. The process according to any one of claims 102-104, wherein the salt is dried prior to or after isolation, optionally wherein the salt is dried under vacuum.
106. The process according to any one of claims 102-105, wherein the salt is dried at from 25 °C to 80 °C, such as at 40°C prior to or after isolation, optionally wherein the salt is dried under vacuum.
107. A pharmaceutical composition comprising a salt of SCO-101 as defined in any one of claims 1- 101; and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents.
108. A salt of SCO-101 as defined in any one of claims 1-101 for use in the treatment of cancer.
109. The salt for use according to claim 108, wherein the treatment further comprises administering one or more anti-cancer agents to a patient having cancer.
110. The salt for use according to any one of claims 108-109, wherein the salt of SCO-101 is administered to the patient daily.
111. The salt for use according to any one of claims 108-110, wherein the one or more anticancer agents are selected from the group consisting of topoisomerase inhibitors, antihormone agents, alkylating agents, mitotic inhibitors, antimetabolites, anti-tumor antibiotics, corticosteroids, targeted anti-cancer therapy, differentiating agents and immunotherapy.
112. The salt for use according to any one of claims 108-111, wherein the anti-cancer agent is administered in combination with one or more further anti-cancer agents.
113. The salt for use according to any one of claims 108-112, wherein the cancer is a solid tumour, such as a solid tumour selected from sarcoma, carcinoma and lymphoma.
114. The salt for use according to any one of claims 108-113, wherein the cancer is selected from the group consisting of colorectal cancer, breast cancer, lung cancer (non small cell lung cancer and small cell lung cancer), one or more glioblastomas, one or more Head and neck cancers, one or more malignant melanomas, basal cell skin cancer, squamous cell skin cancer, liver cancer, pancreatic cancer, prostate cancer, anal cancer, cervix uteri cancer, bladder cancer, corpus uteri cancer, ovarian cancer, gall bladder cancer, one or more sarcomas, one or more leukemias (myeloid and lymphatic), one or more lymphomas, myelomatosis, cholangiocarcinoma, gastric cancer, testicular cancer, uveal cancer, mesothelioma, merkel cell carcinoma, and one or more myelodysplastic syndromes (MDS).
115. The salt for use according to any one of claims 108-114, wherein the cancer is metastatic cancer.
116. The salt for use according to any one of claims 108-115, wherein the cancer is colorectal cancer, such as metastatic colorectal cancer.
117. The salt for use according to any one of claims 108-116, wherein the cancer is pancreatic cancer, such as metastatic pancreatic cancer. 118. The salt for use according to any one of claims 108-117, wherein the cancer is breast cancer, such as metastatic breast cancer.
119. The salt for use according to any one of claims 108-118, wherein the cancer is a resistant cancer which is resistant to the anti-cancer agent when administered alone.
120. The salt for use according to claim 119, wherein the resistance is de novo resistance.
121. The salt for use according to claim 119, wherein resistance is acquired resistance.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2000024707A1 (en) | 1998-10-22 | 2000-05-04 | Neurosearch A/S | Substituted phenyl derivatives, their preparation and use |
WO2017198700A1 (en) | 2016-05-17 | 2017-11-23 | Saniona A/S | Combination treatment of cancer |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000024707A1 (en) | 1998-10-22 | 2000-05-04 | Neurosearch A/S | Substituted phenyl derivatives, their preparation and use |
WO2017198700A1 (en) | 2016-05-17 | 2017-11-23 | Saniona A/S | Combination treatment of cancer |
Non-Patent Citations (3)
Title |
---|
BERGE S M ET AL: "Pharmaceutical Salts", JOURNAL OF PHARMACEUTICAL SCIENCES, AMERICAN CHEMICAL SOCIETY AND AMERICAN PHARMACEUTICAL ASSOCIATION, US, vol. 66, no. 1, 1 January 1977 (1977-01-01), pages 1 - 19, XP000562636, ISSN: 0022-3549, DOI: 10.1002/JPS.2600660104 * |
MINO R CAIRA ED - MONTCHAMP JEAN-LUC: "Crystalline Polymorphism of Organic Compounds", TOPICS IN CURRENT CHEMISTRY; [TOPICS IN CURRENT CHEMISTRY], SPRINGER, BERLIN, DE, vol. 198, 1 January 1998 (1998-01-01), pages 163 - 208, XP008166276, ISSN: 0340-1022, [retrieved on 19990226], DOI: 10.1007/3-540-69178-2_5 * |
STEPHEN BYRN ET AL: "Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations", PHARMACEUTICAL RESEARCH, vol. 12, no. 7, 1 July 1995 (1995-07-01), pages 945 - 954, XP055531015, Retrieved from the Internet <URL:https://link.springer.com/article/10.1023/A:1016241927429> DOI: 10.1023/A:1016241927429 * |
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