Crystalline solid forms of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol
Inventors
Mackenzie, Lloyd F. • Raymond, Jeffery R. • Harwig, Curtis • Fernandez Casares, Ana
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9944590-B2
Publication Date
2018-04-17
Expiration Date
Abstract
The present invention is generally directed to novel crystalline forms of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol and processes for their preparation.
Core Innovation
The described invention relates to crystalline forms of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol, designated as Compound 1 Form A and Compound 1 Form B. The crystalline forms are distinguished from an amorphous form, and each crystalline form is characterized by solid-state analytical techniques.
Compound 1 Form A is characterized by an X-ray powder diffraction (XRPD) pattern with defined peaks at specified 2θ values, and by differential scanning calorimetry (DSC) endothermic events. The document further assigns spectroscopic fingerprinting using FT-IR and Raman, and describes a single-crystal structure and crystal packing/hydrogen-bond features for Form A.
The invention also addresses hydration-related behavior, including stability/resistance to hydrate formation for Form A. In addition, the document includes pharmaceutical compositions and methods of modulating SHIP1 activity by administering Compound 1 Form A or Compound 1 Form B for treating SHIP1-associated diseases/conditions.
Claims Coverage
The partial content identifies one independent claim focused on Compound 1 Form A characterized by a defined XRPD peak set. Dependent claims further cover additional XRPD, DSC, FT-IR, and analytical profiles, and include a preparation method using the amorphous form mixed with selected solvent mixtures.
Compound 1 Form A XRPD peak pattern
A crystalline form of the acetate salt of (1S,3S,4R)-4-((3aS,4R,5S,7aS)-4-(aminomethyl)-7a-methyl-1-methyleneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexanol, designated as Compound 1 Form A, characterized by an X-ray powder diffraction pattern containing peaks at 6.0, 8.9, 10.7, 13.3 and 15.8 degrees 2θ±0.3 degrees 2θ.
Refined Compound 1 Form A XRPD additional peak set
A crystalline form described in claim 1 is further characterized by an X-ray powder diffraction pattern that includes one or more specified diffraction peaks at given 2θ angles within ±0.3 degrees 2θ.
Compound 1 Form A DSC endothermic events
A crystalline form described in claim 1 is further characterized by a DSC thermogram showing specific onset and endothermic peak temperatures for two endothermic events.
Compound 1 Form A FT-IR fingerprint peaks
A crystalline form is further characterized by having one or more FT-IR peaks selected from a specified list of wavenumbers.
Compound 1 Form A multi-method analytical profiles
A specified crystalline form is characterized by one or more specific analytical profiles including XRPD, DSC, TGA, FT-IR, and Raman results as shown in particular tables and figures.
Preparing Compound 1 Form A by solvent mixing with amorphous acetate salt
A method for preparing the crystalline form of claim 1 by mixing the amorphous form of an acetate salt of the specified stereochemical cyclohexanol derivative with selected solvent mixtures consisting of the listed solvents.
Overall, the claim set centers on Compound 1 Form A as a crystalline acetate salt form defined by an XRPD peak pattern, optionally further specified by additional XRPD peaks, DSC endothermic onset/peak temperatures, selected FT-IR peaks, and a multi-method analytical profile set including TGA and Raman, with a preparation method based on mixing the amorphous acetate salt with specified solvent mixtures.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?