Co-crystal forms of selinexor

Patent metadata

Field	Value
Publication number	US-12559478-B2
Application number	US-202117446664-A
Country	US
Kind code	B2
Filing date	Sep 1, 2021
Priority date	Mar 20, 2019
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

The present invention is directed to selinexor co-crystal forms; more particularly to two co-crystal forms with succinic acid as the coformer and a co-crystal form with vanillin as the coformer. The present disclosure is also related to processes for the preparation of selinexor co-crystal forms. Further, the present invention also relates to pharmaceutical compositions comprising a selinexor co-crystal form and method for treating disease using a selinexor co-crystal form.

First claim

What is claimed is:

1 . A selinexor co-crystal comprising selinexor and succinic acid as a coformer.

2 . The selinexor co-crystal of claim 1 , wherein the selinexor co-crystal is crystalline Form I characterized by X-ray powder diffraction peaks at 2θ angles of about 5.2°, 16.7°, 17.0°, 17.6°, and 19.7°.

3 . The selinexor co-crystal of claim 2 , having one to three thermal events with onsets selected from about 121° C., 146° C. and 161° C., as measured by differential scanning calorimetry.

4 . The selinexor co-crystal of claim 1 , characterized by having one or more X-ray powder diffraction peaks selected from 2θ angles of about 5.2°, 16.7°, 17.0°, 17.6° and 19.7°.

5 . The selinexor co-crystal of claim 1 , characterized by having two or more X-ray powder diffraction peaks selected from 2θ angles of about 5.2°, 16.7°, 17.0°, 17.6° and 19.7°.

6 . The selinexor co-crystal of claim 1 , wherein the selinexor co-crystal is crystalline Form II characterized by X-ray powder diffraction peaks at 2θ angles of about 10.4°, 16.6°, 18.9°, and 20.7°.

7 . The selinexor co-crystal of claim 6 , having a thermal event with an onset at about 155° C., as measured by differential scanning calorimetry.

8 . The selinexor co-crystal of claim 1 , characterized by having one or more X-ray powder diffraction peaks selected from 20 angles of about 10.4°, 16.6°, 18.9°, and 20.7°.

9 . The selinexor co-crystal of claim 1 , characterized by having one or more X-ray powder diffraction peaks selected from 2θ angles of about 10.4°, 16.6°, 18.9°, and 20.7°.

10 . A selinexor co-crystal comprising selinexor with vanillin as a coformer.

11 . The selinexor co-crystal of claim 10 , wherein the selinexor co-crystal is crystalline Form I characterized by having X-ray powder diffraction peaks at 2θ angles of about 12.6°, 15.8°, and 19.0°.

12 . The selinexor co-crystal of claim 11 , characterized by having X-ray powder diffraction peaks at 2θ angles of about 12.6°, 14.8°, 15.8°, 19.0°, 20.2°, 25.4°, and 27.9°.

13 . A process for the preparation of selinexor co-crystal of claim 2 , comprising
a) mixing a solution of saturated selinexor and solution of saturated succinic acid in ethyl formate in about 1 (selinexor in ethyl formate): 1 (succinic acid in ethyl formate) mL ratio to form a mixed solution of selinexor and succinic acid in ethyl formate; b) adding to the mixed solution of selinexor and succinic acid in ethyl formate solid selinexor and solid succinic acid in a ratio of about 1 mL (mixed solution of selinexor and succinic acid in ethyl formate): 0.25 mmol (solid selinexor): 0.375 mmol (solid succinic acid) solid succinic acid; c) slurrying the mixed solution with the added selinexor and succinic acid; and d) cooling the solution to yield the selinexor co-crystal.

14 . A process for the preparation of selinexor co-crystal of claim 6 , comprising
a) mixing a solution of selinexor and solution of succinic acid, wherein the solvent of the solution of selinexor or succinic acid is selected from the group consisting of ethyl formate, methanol, 1-propanol, ethyl acetate, isopropanol and acetone, or mixture thereof; to form a mixed solution of selinexor and succinic acid, wherein the ratio of mmol of selinexor:mmol of succinic acid:mL of solvent for selinexor:mL of solvent for succinic acid is about 1 mmol (selinexor): 1-1.5 mmol (succinic acid): 3-4 mL (solvent for selinexor): 3-4 mL (solvent for succinic acid) solvent for succinic acid, b) adding to the mixed solution of selinexor and succinic acid an anti-solvent, wherein the ratio of mL of mixed solution for selinexor and succinic acid:mL of anti-solvent is about 1 mL (mixed solution for selinexor and succinic acid): 2-4 mL (anti-solvent) anti-solvent; and c) cooling the mixture of step b) to yield the selinexor co-crystal.

15 . A process for preparing selinexor co-crystal of claim 10 , comprising
a) mixing a solution of dissolved selinexor and solution of dissolved vanillin in tetrahydrofuran in about 1 (selinexor in tetrahydrofuran): 1 (vanillin in tetrahydrofuran) mL ratio to form a mixed solution of selinexor and vanillin in tetrahydrofuran; b) adding to the mixed solution of selinexor and vanillin in tetrahydrofuran solid selinexor and solid vanillin in a ratio of about 1 mL (mixed solution of selinexor and vanillin in tetrahydrofuran) mixed solution of selinexor and vanillin in tetrahydrofuran: 0.25 mmol (solid selinexor) solid selinexor: 0.26 mmol (solid vanillin) solid vanillin; c) slurrying the mixed solution with the added selinexor and vanillin; and d) cooling the solution to yield the selinexor co-crystal.

16 . The selinexor co-crystal of claim 2 , characterized by having X-ray powder diffraction peaks at 2θ angles of about 5.2°, 10.4°, 16.7°, 17.0°, 17.6°, 19.5°, 19.7°, 20.4°, 21.8°, and 22.9°.

17 . The selinexor co-crystal of claim 2 , characterized by having X-ray powder diffraction peaks at 2θ angles of about 5.2°, 7.1°, 10.4°, 11.3°, 12.1°, 16.7°, 17.0°, 17.6°, 19.5°, 19.7°, 20.4°, 21.8°, and 22.9°.

18 . The selinexor co-crystal of claim 6 , characterized by having X-ray powder diffraction peaks at 2θ angles of about 5.7°, 10.4°, 14.2°, 16.6°, 18.9°, 20.7°, 21.4°, 22.2°, 23.0°, 24.5°, 25.9°, 26.6°, and 27.6°.

19 . The selinexor co-crystal of claim 6 , characterized by having X-ray powder diffraction peaks at 2θ angles of about 5.7°, 10.4°, 16.6°, 18.9°, 20.7°, 21.4°, 24.5°, 26.6°, and 27.6°.

Assignees

• Karyopharm Therapeutics Inc

Inventors

• Hamilton Clifton

Classifications

• C07C55/10

  Succinic acid · CPC title

• C07C47/58

  Vanillin · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/497

  containing further heterocyclic rings · CPC title