US-20260125390-A1 - SOLID FORMS OF MACROCYCLIC COMPOUNDS, SALTS AND FORMULATIONS THEREOF, AND METHODS OF PREPARING AND USING THE SAME

Abstract

The present disclosure relates to solid forms of Compound 1, or a pharmaceutically acceptable form thereof, a pharmaceutically acceptable salt of Compound 1, or pharmaceutically acceptable solvate thereof, pharmaceutical compositions comprising the same, methods of preparing the same, and methods of treating cancer dependent on a farnesylated protein, using the same.

Inventors

• Roger Paul BAKALE
• Ana Rita Neves
• Kenneth K. Liu
• Yun Shan
• Xiufeng Sun
• Patricia Andres
• Song Chen
• Yue Lu
• Licheng Song
• Catalina FERRER

Assignees

• KURA ONCOLOGY, INC.

Dates

Publication Date

20260507

Application Date

20251003

Priority Date

20230531

Claims (20)

1. 1 . A solid form comprising Compound 1, or a pharmaceutically acceptable salt and/or solvate thereof:
2. 2 - 127 . (canceled)
3. 128 . A compound, wherein the compound is: i) a pharmaceutically acceptable salt of Compound 1: or an isotopologue thereof, or a pharmaceutically acceptable solvate of the pharmaceutically acceptable salt of the Compound 1 or isotopologue thereof; or ii) a (R)-chlocyphos, (S)-chlocyphos, (+)-tartaric acid, (−)-tartaric acid, (+)-camphorsulfonic acid, (−)-camphorsulfonic acid, L-(−)-di-p-anisoyltartaric acid, D-(+)-di-p-anisoyltartaric acid, L-(−)-di-toluoyltartaric acid, D-(+)-di-toluoyltartaric acid, (R)-BINAP phosphate, (S)-BINAP phosphate, di-benzoyl-l-tartaric acid, or di-benzoyl-D-tartaric acid salt of Compound 1 or Compound 2:
4. 129 . The compound of claim 297 , wherein the pharmaceutically acceptable salt is a benzoate salt, a besylate salt, a chloride salt, a citrate salt, a fumarate salt, a gentisate salt, a glutarate salt, a glycolate salt, a hippurate salt, a 1-hydroxy-2-naphthoate salt, a malate salt, a maleate salt, a mesylate salt, an oxalate salt, a phosphate salt, a sulfate salt, a tartrate salt, or a tosylate salt.
5. 130 - 151 . (canceled)
6. 152 . The compound of claim 297 , wherein the pharmaceutically acceptable salt of the Compound 1 or isotopologue thereof is a non-solvate of the pharmaceutically acceptable salt of the Compound 1 or isotopologue thereof.
7. 153 . (canceled)
8. 154 . The compound of claim 297 , wherein the pharmaceutically acceptable salt of the Compound 1 or isotopologue thereof is a pharmaceutically acceptable solvate of the pharmaceutically acceptable salt of the Compound 1 or isotopologue thereof.
9. 155 . The compound of claim 154 , wherein the pharmaceutically acceptable solvate is a hydrate, an iso-butyl acetate, an iso-propyl acetate, a tetrahydrofuran solvate, an acetone solvate, an acetonitrile solvate, or combinations thereof.
10. 156 - 158 . (canceled)
11. 159 . A pharmaceutical composition comprising: i) the solid form of claim 1 in an amount from about 0.1 mg to about 200 mg; and ii) one or more pharmaceutically acceptable excipients.
12. 160 . The pharmaceutical composition of claim 159 , wherein the solid form is crystalline.
13. 161 - 166 . (canceled)
14. 167 . The pharmaceutical composition of claim 160 , wherein the solid form is Compound 1 (Form 1).
15. 168 . The pharmaceutical composition of claim 159 , wherein the pharmaceutical composition is formulated as an immediate release oral dosage form.
16. 169 . The pharmaceutical composition of claim 159 , wherein the pharmaceutical composition is a tablet.
17. 170 . The pharmaceutical composition of claim 169 , wherein the tablet is a coated tablet.
18. 171 - 204 . (canceled)
19. 205 . A method of preparing the pharmaceutical composition of claim 159 , the method comprising: i) optionally, de-lumping the solid form; ii) mixing the solid form with a disintegrant, a glidant, and a first portion of a filler to form a first blend; iii) de-lumping the first blend to form a de-lumped first blend; iv) de-lumping a second portion of the filler; v) blending the de-lumped first blend and the de-lumped second portion of the filler to form a second blend; vi) blending the second blend with a lubricant to form a lubricated blend; and vii) compressing the lubricated blend, optionally with a rotary press, into a tablet; or the method comprising: i) optionally, de-lumping the solid form; ii) mixing the solid form with a filler, a glidant, and a first portion of a disintegrant to form a first blend; iii) de-lumping and then blending the first blend to form a second blend; iv) blending the second blend with a first portion of a lubricant to form a lubricated intragranular blend; v) forming granules from the intragranular blend; vi) blending the granules with a second portion of the disintegrant and a second portion of the lubricant to form a lubricated final blend; and vii) compressing the lubricated final blend, optionally with a rotary press, into a tablet; or the method comprising: i) optionally, de-lumping the solid form; ii) granulating the solid form with a filler, a glidant, and a disintegrant with a binder and water to form wet granules; iii) drying the wet granules to form dry granules; iv) blending the granules with a lubricant to form a lubricated final blend; and v) compressing the lubricated final blend, optionally with a rotary press, into a tablet.
20. 206 - 219 . (canceled)

Description

1. CROSS-REFERENCE This application claims the benefit of priority from International Patent Application No. PCT/CN2023/097389, filed May 31, 2023, which is herein incorporated by reference in its entirety. 2. FIELD Provided herein are solid forms of Compound 1, or a pharmaceutically acceptable form thereof, a pharmaceutically acceptable salt of Compound 1, or pharmaceutically acceptable solvate thereof, pharmaceutical compositions comprising the same, methods of preparing the same, and methods of treating cancer dependent on a farnesylated protein, using the same. 3. SUMMARY In one aspect is solid form comprising Compound 1, or a pharmaceutically acceptable salt and/or solvate thereof: In another aspect is a pharmaceutically acceptable salt of Compound 1, or an isotopologue thereof, or a pharmaceutically acceptable solvate of the pharmaceutically acceptable salt. In another aspect is a pharmaceutical composition comprising: i) a solid form comprising Compound 1, or a pharmaceutically acceptable salt and/or solvate thereof, in an amount from about 0.1 mg to about 200 mg, and ii) one or more pharmaceutically acceptable excipients. In another aspect is a method of preparing a pharmaceutical composition, as provided herein, comprising: i) optionally, de-lumping the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof; ii) mixing the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof, with a disintegrant, a glidant, and a first portion of a filler to form a first blend; iii) de-lumping the first blend to form a de-lumped first blend; iv) de-lumping a second portion of the filler; v) blending the de-lumped first blend and the de-lumped second portion of the filler to form a second blend; vi) blending the second blend with a lubricant to form a lubricated blend; and vii) compressing the lubricated blend, optionally with a rotary press, into a tablet. In another aspect is a method of preparing a pharmaceutical composition, as provided herein, comprising: i) optionally, de-lumping the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof; ii) mixing the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof, with a filler, a glidant, and a first portion of a disintegrant to form a first blend; iii) de-lumping and then blending the first blend to form a second blend; iv) blending the second blend with a first portion of a lubricant to form a lubricated intragranular blend; v) forming granules from the intragranular blend, for example, with a roller compactor and screen; vi) blending the granules with a second portion of the disintegrant and a second portion of the lubricant to form a lubricated final blend; and vii) compressing the lubricated final blend, optionally with a rotary press, into a tablet. In another aspect is a method of preparing the pharmaceutical composition, as provided herein, comprising: i) optionally, de-lumping the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof; ii) granulating the solid form of the Compound 1, or pharmaceutically acceptable salt and/or solvate thereof, a filler, a glidant, and a disintegrant with a binder and water to form wet granules; iii) drying the wet granules to form dry granules; iv) blending the granules with a lubricant to form a lubricated final blend; and v) compressing the lubricated final blend, optionally with a rotary press, into a tablet. In another aspect is a process for preparing Compound 1: or a pharmaceutically acceptable form thereof, comprising: (a) reacting racemic Compound 19: with a chiral acid in a solvent to form a diastereomeric salt of Compound 1 and a diastereomeric salt of Compound 2: wherein one of the two diastereomeric salts precipitates selectively from the solvent and the other of the two diastereomeric salts is selectively soluble in the solvent;(b) separating the precipitate from the solvent;(c) reacting the diastereomeric salt of Compound 1 with a base to provide Compound 1, and(d) optionally, recrystallizing Compound 1, optionally from ACN/water in a ratio of about 2:1 to about 1:5, optionally about 1:1 to about 1:3. In another aspect is a process for preparing Compound 1: or a pharmaceutically acceptable form thereof, comprising reacting Compound 18A: with a cyanide equivalent and a palladium catalyst, optionally in the presence of zinc source and/or a phosphine ligand, to provide Compound 19: and purifying racemic Compound 19 by chiral separation to provide Compound 1. In another aspect is a process for preparing Compound 9 comprising reacting Compound 7: with a demethylating agent to form Compound 8: and reacting Compound 8 with TBSCl and a base to form Compound 9. In another aspect is a process for preparing Compound 11: comprising reacting Compound 23: with TBSCl in the presence of a base to form Compound 11. In another aspect is a process for prepari