Ion channel modulators
Inventors
Griffin, Andrew Mark • Marron, Brian Edward • MARTINEZ BOTELLA, Gabriel • Reddy, Kiran • Wittmann, Marion
Assignees
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Publication Number
US-11866439-B2
Publication Date
2024-01-09
Expiration Date
Abstract
The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.
Core Innovation
The disclosure relates to a crystalline form of a compound characterized by an X-ray powder diffraction pattern comprising peaks at diffraction angles (° 2θ) of 12.6±0.2, 15.8±0.2, and 18.6±0.2. Related embodiments include additional XRPD peak constraints at 10.7±0.2, 12.3±0.2, and 22.6±0.2, and the XRPD pattern optionally substantially matches the one shown in FIG. 5A.
The crystalline form is further characterized by differential scanning calorimetry, including a melting-point onset of about 107°C, and by obtaining the XRPD pattern using Cu Kα radiation. The disclosure includes crystalline embodiments of substituted pharmaceutical compounds, including Formula I, I-a, I-b, I-c, I-d, II, III, V, VII, VIII, and IX, as well as fused heteroaryl ion-channel modulator compounds and related fluorinated heteroaromatic derivatives.
The compounds target voltage-gated sodium channels by modulating abnormal late/persistent sodium current (INaL). The disclosure also includes pharmaceutical compositions and methods of treatment involving administering the disclosed compounds or their crystalline forms, including embodiments as pharmaceutically acceptable salts, optionally with a pharmaceutically acceptable carrier.
Claims Coverage
The independent claims cover crystalline forms defined by specific XRPD peak patterns, with six inventive features appearing across the provided claim summaries. Dependent coverage further refines the XRPD peak set, ties the pattern to FIG. 5A, adds a DSC melting-onset constraint, specifies Cu Kα measurement conditions, and extends to pharmaceutical compositions with a pharmaceutically acceptable carrier.
Crystalline form characterized by specified XRPD peaks
A crystalline form of compound characterized by an X-ray powder diffraction pattern comprising X-ray powder diffraction peaks at diffraction angles (° 2θ) of 12.6±0.2, 15.8±0.2, and 18.6±0.2.
Crystalline form characterized by expanded XRPD peak set
A crystalline form characterized by an X-ray powder diffraction pattern comprising X-ray powder diffraction peaks at diffraction angles (° 2θ) of 10.7±0.2, 12.3±0.2, 12.6±0.2, 15.8±0.2, 18.6±0.2, and 22.6±0.2.
Crystalline form matching FIG. 5A
The crystalline form characterized by an X-ray powder diffraction pattern substantially matching the one shown in FIG. 5A.
Crystalline form with DSC melting-point onset constraint
A crystalline form characterized by a melting-point onset of about 107°C as determined by differential scanning calorimetry (DSC).
Crystalline form characterized by Cu Kα XRPD measurement
The crystalline form characterized by obtaining an X-ray powder diffraction pattern using Cu Kα radiation.
Pharmaceutical composition including the crystalline form with carrier
A pharmaceutical composition including the crystalline form together with a pharmaceutically acceptable carrier.
Overall, the claim coverage centers on crystalline forms defined by specified XRPD peak angles, with dependent refinements that expand the XRPD peak set, match FIG. 5A, add a DSC melting-onset constraint, specify Cu Kα measurement, and extend the crystalline form into pharmaceutical compositions with a pharmaceutically acceptable carrier.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating neurological, psychiatric, pain, and related disorders.
Treating epilepsy syndromes including Dravet syndrome, Lennox-Gastaut syndrome, and infantile spasms.
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