(4-((3R,4R)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4-yl)methanone citrate
Inventors
Ostermeier, Markus • Werthmann, Ulrike
Assignees
Boehringer Ingelheim International GmbH • Centrexion Therapeutics Corp
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Publication Number
US-12076321-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The invention provides a salt of a tetrahydropyranylmethylaminopyrimidine amide, such as the citrate salt of (4-((3R,4R)-3-methoxytetrahydropyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4-yl)methanone, pharmaceutical compositions containing the same, processes for preparing the same, and methods of medical treatment using the same.
Core Innovation
The invention relates to a tetrahydropyranylmethylaminopyrimidine amide CCR2 antagonist provided as a citrate salt, identified as compound I citrate (citrate salt 1). The document distinguishes the crystalline citrate salt 1 from an amorphous free base and from other salts, emphasizing solid-form behavior and solid-state properties.
The document states that citrate salt 1 is crystalline and has one polymorph only, in contrast to hydrobromide and hydrochloride polymorphs. It further describes hygroscopicity and water uptake using dynamic vapour sorption, stating low water uptake at 80% RH and 90% RH, and non-deliquescent behavior relative to other salts that exhibit deliquescence.
Citrate salt 1 is characterized by defined solid-state measurements, including XRPD peak positions, Raman shifts, and a melting point of 212±5°C. The document also includes a treatment scope and formulation/medical-use context for CCR2-related conditions, including pain due to osteoarthritis and other CCR2-related inflammatory conditions.
Claims Coverage
The provided claims include one independent method claim and multiple dependent claims that refine the method by focusing on the use of a crystalline solid form of a compound of Formula 1 and specifying XRPD-based characterization constraints, including measurement conditions and quantitative intensity thresholds.
Oral treatment of osteoarthritis pain using a compound of Formula 1
A method of treating pain due to osteoarthritis comprising orally administering to a patient in need thereof a therapeutically effective amount of a compound of Formula 1 to treat the pain due to osteoarthritis.
Crystalline solid form of compound of Formula 1
The method uses the compound of Formula 1 in crystalline form.
Crystalline form characterized by XRPD peak pattern with CuKα and defined conditions
A crystalline form characterized by a specified X-ray powder diffraction peak pattern at defined 2-theta values measured with monochromatic CuKα radiation under specified conditions.
Crystalline form characterized by an XRPD table of 2θ, d-spacing, and relative intensities
The crystalline form is characterized by an X-ray powder diffraction pattern specified as diffraction angles (2θ), inter-planar distances (d), and relative intensities (percent of the most intense peak).
Minimum relative intensity for a specified XRPD peak
The relative intensity of the X-ray diffraction peak at specified diffraction angles is at least 10%.
Treatment in a human patient
The method is applied to a human patient.
Overall, the claims cover an oral treatment method for osteoarthritis pain using a compound of Formula 1, with key refinements requiring crystalline solid form characterized by XRPD peak patterns under specified measurement conditions, including quantitative relative intensity constraints.
Stated Advantages
One polymorph only for the crystalline citrate salt 1, contrasted with multiple polymorphs reported for hydrobromide and hydrochloride.
Low and reversible water uptake at 80% RH and 90% RH.
Non-deliquescent behavior of citrate salt 1 relative to salts that deliquesce.
Defined solid-state characterization of citrate salt 1 using XRPD and Raman, including specific reported peak positions and melting point (212±5°C).
Documented Applications
Treatment of pain due to osteoarthritis via oral administration of a therapeutically effective amount of a compound of Formula 1.
Treatment of CCR2-related inflammatory conditions is described as part of the medical-use scope, including osteoarthritis pain (knee, hip, and hand).
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