Solid forms of a modulator of hemoglobin
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.
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 .