Solid forms of a modulator of hemoglobin

Patent metadata

Field	Value
Publication number	US-12473277-B2
Application number	US-202318499491-A
Country	US
Kind code	B2
Filing date	Nov 1, 2023
Priority date	May 14, 2021
Publication date	Nov 18, 2025
Grant date	Nov 18, 2025

Abstract

Forms of (S)-2-hydroxy-6-((4-(2-(2-hydroxyethyl)nicotinoyl)morpholin-3-yl)methoxy)benzaldehyde (Compound I), or salts or solvates thereof, were prepared and characterized in the solid state. Also provided are processes of manufacture and methods of using the forms of Compound I.

First claim

What is claimed is:

1 . A crystalline Compound I Besylate Form A having the formula:

wherein X is benzenesulfonic acid, and wherein the crystalline Compound I Besylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 4.93±0.2, 15.7±0.2, 17.0±0.2, 18.5±0.2, 19.2±0.2, and 22.4±0.2, as determined on a diffractometer using Cu-Kα radiation.

2 . A crystalline Compound I Edisylate Form A having the formula:

wherein X is 1,2-ethanedisulfonic acid, and wherein the crystalline Compound I Edisylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 4.99±0.2, 11.5±0.2, 18.6±0.2, 21.1±0.2, and 23.9±0.2, as determined on a diffractometer using Cu-Kα radiation.

3 . A crystalline Compound I Esylate Form A having the formula:

wherein X is 1,2-ethanedisulfonic acid, and wherein the crystalline Compound I Esylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 11.2±0.2, 18.5±0.2, 19.2±0.2, 21.4±0.2, and 22.5±0.2, as determined on a diffractometer using Cu-Kα radiation.

4 . A crystalline Compound I Napadisylate Form A having the formula:

wherein X is naphthalene-1,5-disulfonic acid, and wherein the crystalline Compound I Napadisylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 5.26±0.2, 10.6±0.2, 12.1±0.2, 17.8±0.2, 19.5±0.2, and 20.7±0.2, as determined on a diffractometer using Cu-Kα radiation.

5 . A crystalline Compound I Napsylate Form A having the formula:

wherein X is naphthalene-2-sulfonic acid, and wherein the crystalline Compound I Napsylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 15.0±0.2, 15.1±0.2, 17.4±0.2, 20.0±0.2, and 24.0±0.2, as determined on a diffractometer using Cu-Kα radiation.

6 . A crystalline Compound I Sulfate Form A having the formula:

wherein X is sulfuric acid, and wherein the crystalline Compound I Sulfate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 10.7±0.2, 11.6±0.2, 18.2±0.2, 19.3±0.2, 20.8±0.2, and 23.5±0.2 as determined on a diffractometer using Cu-Kα radiation.

7 . A crystalline Compound I Tosylate Form A having the formula:

wherein X is p-toluenesulfonic acid, and wherein the crystalline Compound I Tosylate Form A is characterized by an X-ray powder diffractogram comprising diffraction peaks 4.68±0.2, 17.7±0.2, 18.6±0.2, 19.1±0.2, and 23.4±0.2 as determined on a diffractometer using Cu-Kα radiation.

8 . A pharmaceutical composition comprising the crystalline Compound I Besylate Form A of claim 1 , and a pharmaceutically acceptable excipient.

9 . A pharmaceutical composition comprising the crystalline Compound I Edisylate Form A of claim 2 and a pharmaceutically acceptable excipient.

10 . A pharmaceutical composition comprising the crystalline Compound I Esylate Form A of claim 3 and a pharmaceutically acceptable excipient.

11 . A pharmaceutical composition comprising the crystalline Compound I Napadisylate Form A of claim 4 and a pharmaceutically acceptable excipient.

12 . A pharmaceutical composition comprising the crystalline Compound I Napsylate Form A of claim 5 and a pharmaceutically acceptable excipient.

13 . A pharmaceutical composition comprising the crystalline Compound I Sulfate Form A of claim 6 and a pharmaceutically acceptable excipient.

14 . A pharmaceutical composition comprising the crystalline Compound I Tosylate Form A of claim 7 and a pharmaceutically acceptable excipient.

15 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Besylate Form A of claim 1 .

16 . A method of treating sickle cell disease in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of claim 8 .

17 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Edisylate Form A of claim 2 .

18 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Esylate Form A of claim 3 .

19 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Napadisylate Form A of claim 4 .

20 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Napsylate Form A of claim 5 .

21 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Sulfate Form A of claim 6 .

22 . A method for treating sickle cell disease in a subject in need thereof, comprising administering to the subject the crystalline Compound I Tosylate Form A of claim 7 .

Assignees

• Global Blood Therapeutics Inc

Inventors

• Parent Stephan D
• Houston Travis Lee
• Johnson Courtney S
• Wang Fang

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D413/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title