Salts, co-crystals, and polymorphs of an anxiolytic compound
Inventors
Flynn, Bernard Luke • Paul, Dharam • Harvey, Andrew John • SETHURAMAN, Vasu V. • Forslund, Raymond E. • Xue, Song • LIVINGSTON, Rob • Hashash, Ahmad
Assignees
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Publication Number
US-9745296-B2
Publication Date
2017-08-29
Expiration Date
Abstract
The present invention provides amorphous arid crystalline forms of 1-ethyl-6-(indan-2-ylamino)-3-(morpholine-4-carbonyl)-1,8-naphthyridin-4-one (compound 1), and salts, co-crystals, and pharmaceutical compositions thereof. The invention also provides methods of treating and/or preventing a disease, such as a central nervous system disease (e.g., an anxiety disorder), using the amorphous and crystalline forms, and salts, co-crystals, and pharmaceutical compositions thereof.
Core Innovation
The disclosure characterizes compound 1 and its solid-state forms as amorphous and crystalline forms, including polymorphs and solvate and hydrate forms, as well as acid addition salts, co-crystal and salt-derived forms, and succinate-derived forms SUC-P3, SUC-P4, and SUC-P5. The solid-state forms are defined and distinguished by instrumental characterization datasets including XRPD, Raman, DSC, DVS, TG-FTIR, and IR, together with physical attributes such as impurity thresholds, anhydrous or solvated status, and melting point ranges.
Crystalline Form SUC-P5 is specifically described as a crystalline form with identity based on analytical characterization constraints. These include XRPD diffraction pattern features with selected 2-Theta angles and a DSC thermogram endotherm peak temperature of about 207°C, together with distinctions among anhydrous and solvate materials and stability or humidity behavior.
The disclosure also describes pharmaceutical compositions containing the identified salt and solid forms of compound 1, with pharmaceutical use focused on central nervous system disease. Therapeutic use categories explicitly include anxiety disorders, mood and anxiety disorders, and neurodegenerative diseases, and the document enumerates anxiety disorder categories using diagnostic framework language together with depression criteria.
Claims Coverage
The claims coverage centers on one independent claim that defines a specific solid-state salt form, namely a hemi-succinate salt of crystalline Form SUC-P5 of compound 1. The main scope is refined by dependent claims that add purity and analytical characterization requirements, and further by claims directed to pharmaceutical compositions and therapeutic treatment of specified indications.
Hemi-succinate salt of crystalline Form SUC-P5 of compound 1
A hemi-succinate salt of the crystalline Form SUC-P5 of compound 1.
Substantially free of impurities and amorphous compound 1
The crystalline Form SUC-P5 is substantially free of impurities and of amorphous compound 1.
Xrpd-defined crystalline Form SUC-P5
The crystalline Form SUC-P5 is characterized by having two or more peaks in its x-ray powder diffraction pattern at selected 2-Theta angles of 7.4, 15.6, 16.5, 18.5, and 22.2.
Dsc-defined crystalline Form SUC-P5
The crystalline Form SUC-P5 is characterized by a DSC thermogram whose endotherm peak temperature is about 207°C.
Pharmaceutical composition comprising crystalline Form SUC-P5
A pharmaceutical composition includes the crystalline form SUC-P5 and optionally a pharmaceutically acceptable excipient.
Treatment of selected anxiety disorders
A method for treating anxiety disorders selected from panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), substance-induced anxiety disorder, acute stress disorder (ASD), irritable bowel syndrome, or fibromyalgia.
Overall, the claim set protects the specific hemi-succinate salt of crystalline Form SUC-P5 of compound 1, with defining constraints based on XRPD peak positions and a DSC endotherm Tmax value, along with purity limitations. Additional claim scope is directed to formulation in a pharmaceutical composition and to therapeutic methods for CNS indications, including selected anxiety disorders as enumerated.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Pharmaceutical composition use for central nervous system disease, including anxiety disorders, mood and anxiety disorders, and neurodegenerative diseases.
Treating and/or preventing central nervous system disease, including anxiety disorders, using the disclosed solid forms and pharmaceutical compositions.
Treatment of anxiety disorders specifically selected from panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), substance-induced anxiety disorder, acute stress disorder (ASD), irritable bowel syndrome, or fibromyalgia.
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