Crystalline forms of gepotidacin

Patent metadata

Field	Value
Publication number	US-12528809-B2
Application number	US-202117997293-A
Country	US
Kind code	B2
Filing date	Apr 27, 2021
Priority date	Apr 29, 2020
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

Disclosed are novel crystalline forms of gepotidacin and pharmaceutical compositions containing the same. Also disclosed are processes for the preparation thereof and methods for use thereof.

First claim

The invention claimed is:

1 . A crystalline form of gepotidacin, which is selected from the group consisting of gepotidacin mesylate anhydrate, gepotidacin mesylate monohydrate, gepotidacin mesylate dihydrate and gepotidacin anhydrate.

2 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate dihydrate.

3 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate dihydrate characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu K α radiation, selected from the group consisting of about 9.0, 11.5, 13.4, 14.3, 14.9, 15.5, 17.6, 18.6, and 20.7 degrees 2θ.

4 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate dihydrate characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 1 .

5 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate dihydrate characterized by the following unit cell parameters:
a=6.9255(5)Å; b=15.4500(12)Å; c=25.7918(19)Å; α=β=γ=90°; V=2759.7(4)Å 3 ; Z′=1; Space group P2 1 2 1 2 1 ; Molecules/unit cell 4; Density (calculated) 1.398 g/cm 3 ; wherein Z′ is the number of molecules per asymmetric unit.

6 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate anhydrate.

7 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate anhydrate characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu K α radiation, selected from the group consisting of about 7.1, 9.7, 12.1, 14.2, 15.2, 17.3, and 20.2 degrees 2θ.

8 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate anhydrate characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 5 .

9 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate anhydrate characterized by the following unit cell parameters:
a=12.3921(7)Å; b=7.0262(4)Å; c=14.6536(9)Å; α=γ=90°; β=95.0077(13)°; V=1271.01(13)Å3; Z′=1 Space group P2 1 ; Molecules/unit cell 2; Density (calculated) 1.423 g/cm 3 ; wherein Z′ is the number of molecules per asymmetric unit.

10 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate monohydrate.

11 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate monohydrate characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu Ka radiation, selected from the group consisting of about 5.6, 7.1, 8.8, 11.2, 13.0, 13.7, 20.1, 21.6, and 23.3 degrees 2θ.

12 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin mesylate monohydrate characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 9 .

13 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin anhydrate characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu K α radiation, selected from the group consisting of about 8.8, 10.8, 11.7, 12.8, 13.2, 14.4, 16.3, 19.9, 20.8, and 25.0 degrees 2θ.

14 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin anhydrate.

15 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin anhydrate characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 13 .

16 . The crystalline form according to claim 1 , wherein the crystalline form is gepotidacin anhydrate characterized by the following unit cell parameters:
a=8.44022(16)Å; b=6.42442(12)Å; c=20.2774(5)Å; α=γ=90°; β=96.778(2)°; V=1091.83(4)Å 3 ; Z′=1 Space group P2 1 ; Molecules/unit cell 2; Density (calculated) 1.364 g/cm 3 ; wherein Z′ is the number of molecules per asymmetric unit.

17 . A pharmaceutical composition comprising the crystalline form according to claim 1 and a pharmaceutically acceptable carrier.

18 . The pharmaceutical composition according to claim 17 , wherein the pharmaceutical composition is for oral administration.

19 . The pharmaceutical composition according to claim 18 , wherein the pharmaceutical composition is a tablet or capsule.

20 . A method of preparing a pharmaceutical composition comprising gepotidacin, which method comprises mixing the crystalline form according to claim 1 and a pharmaceutically acceptable carrier.

21 . A method of treating a bacterial infection in a human in need thereof comprising administering to said human an effective amount of the crystalline form according to claim 1 .

22 . The method according to claim 21 , wherein the bacterial infection is uncomplicated urinary tract infection or infection by Neisseria gonorrhoeae.

23 . A method for preparing gepotidacin mesylate dihydrate comprising crystallizing gepotidacin mesylate in a solvent mixture of water and an organic solvent.

24 . The method according to claim 23 , wherein the organic solvent is 2-propanol.

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Couch Ricky Wayne
• Dai Wenning
• Davison Senthil
• Pendrak Israil
• Williams Glenn Robert

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D471/16 Primary

  Peri-condensed systems · CPC title