Crystalline forms of a somatostatin modulator
Inventors
Zhao, Yuxin • REDDY, Jayachandra P. • MacEachern, Lauren • KAHWAJI, Samer • MONYONCHO, Evans • Mueller, Peter
Assignees
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Publication Number
US-11773076-B2
Publication Date
2023-10-03
Expiration Date
Abstract
Described herein are crystalline forms of 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, uses of such crystalline forms in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a somatostatin modulator compound.
Core Innovation
The disclosed invention relates to solid-state forms of a somatostatin (SST) modulator identified as 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide (Compound 1). The disclosure includes crystalline Pattern A, crystalline Pattern B, crystalline Pattern C, crystalline Pattern D, and an amorphous form of Compound 1, with characterization of the solid forms by X-Ray Powder Diffraction (XRPD).
Crystalline Pattern A is characterized by an XRPD pattern with peaks at specified 2-Theta values measured with Cu Kα1 radiation, and the other crystalline patterns are defined by XRPD patterns substantially the same as shown in specific figures as measured with Cu Kα1 radiation. The disclosure further characterizes the solid forms using thermal and moisture-related analyses, including DSC and TGA thermal events and hygroscopicity via Dynamic Vapor Sorption (DVS) with reversible water uptake and humidity/storage stability assessments.
The disclosure also includes unit-cell parameters for a monohydrate form of Compound 1 at 100 K, including a defined space group, and states that crystalline Pattern A can be substantially free of impurities and other solid forms. Pharmaceutical compositions comprising crystalline or amorphous forms are described for oral administration.
The therapeutic rationale centers on modulating somatostatin receptor subtypes, including SSTR5 agonism, for treating conditions such as hyperinsulinism and hyperinsulinemic hypoglycemia.
Claims Coverage
The independent claim set covers four inventive features: crystalline forms of Compound 1 defined by XRPD characteristics for crystalline Patterns A, B, C, and D.
Crystalline pattern defined by XRPD peaks for Pattern A
A crystalline form of Compound 1 characterized as crystalline Pattern A having an XRPD pattern with peaks at 9.4±0.2, 12.9±0.2, 13.3±0.2, 17.1±0.2, 18.8±0.2, 19.3±0.2, and 20.7±0.2 2-Theta as measured with Cu Kα1 radiation.
Crystalline pattern defined by XRPD substantially the same as FIG. 4 for Pattern B
A crystalline form of Compound 1 characterized as crystalline Pattern B having an XRPD pattern substantially the same as shown in FIG. 4 as measured with Cu Kα1 radiation.
Crystalline pattern defined by XRPD substantially the same as FIG. 6 for Pattern C
A crystalline form of Compound 1 characterized as crystalline Pattern C having an XRPD pattern substantially the same as shown in FIG. 6 as measured with Cu Kα1 radiation.
Crystalline pattern defined by XRPD substantially the same as FIG. 7 for Pattern D
A crystalline form of Compound 1 characterized as crystalline Pattern D having an XRPD pattern substantially the same as shown in FIG. 7 as measured with Cu Kα1 radiation.
The independent claim coverage defines crystalline forms of Compound 1 through XRPD characteristics, either by explicit peak positions for crystalline Pattern A or by XRPD patterns substantially the same as shown in specified figures for crystalline Patterns B, C, and D.
Stated Advantages
Substantially free of impurities and other solid forms.
Documented Applications
Treating hyperinsulinism in a mammal by administering the crystalline form.
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