RXR agonist salt form, polymorphs thereof, and uses thereof
AssigneeIo Therapeutics, Inc.
InventorsVidyasagar Vuligonda, Martin E. Sanders, Shanming Kuang, Harsh Shailesh Shah
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Abstract
Provided herein are salt and solid forms of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, including a Tris salt form of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, and polymorphs thereof, methods of preparing the compounds, and their uses.
Claims9
A solid form of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, which is a a lysine salt or a glycine salt of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid.
A method for preparing a solid form which is Form A of the salt (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid mono-(tris (hydroxymethyl)aminomethane) having an X-ray powder diffraction pattern comprising a signal, in terms of 2θ, at 11.3±0.2°, the method comprising:
- heating a solid Form C of tris(hydroxymethyl)aminomethane salt of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, optionally having an X-ray powder diffraction pattern comprising one or more signals, in terms of degrees 2θ, selected from 2.9±0.2°, 5.5±0.2°, 5.9±0.2°, or 28.9±0.2°, and optionally having a differential scanning calorimetry thermogram comprising endothermic transitions at 94±3° C. and 152±3° C. to obtain the solid Form A of the salt (25,4E)-3-methyl-5-((15,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic mono-acid (tris(hydroxymethyl)aminomethane).
A method for preparing a solid form which is Form A of the salt (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid mono-tris(hydroxymethyl)aminomethane) having an X-ray powder diffraction pattern comprising a signal, in terms of 2θ, at 11.3±0.2°, the method comprising:
- heating a solid Form D of the tris(hydroxymethyl)aminomethane salt of (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid, optionally having an X-ray powder diffraction pattern comprising one or more signals, in terms of degrees 2θ, selected from 3.9±0.2°, 11.8±0.2°, 17.6±0.2°, or 32.7±0.2°, and optionally having a differential scanning calorimetry thermogram comprising endothermic transitions at 61±3° C., and 154±3° C. to obtain the solid Form A of the salt (2E,4E)-3-methyl-5-((1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl)penta-2,4-dienoic acid mono-(tris(hydroxymethyl)aminomethane).
Dependencies are inferred from the claim text.