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-10266529-B2
Publication Date
2019-04-23
Expiration Date
Abstract
The present invention provides crystalline Forms FUM-P3, FUM-P4, MLA-P3 and MLA-P4 of compound formula 1 and related methods of treating and/or preventing a disease, such as a central nervous system disease (e.g., an anxiety disorder), using a crystalline Form FUM-P3, FUM-P4, MLA-P3 and MLA-P4 of compound formula 1 and/or pharmaceutical compositions thereof.
Core Innovation
The invention relates to crystalline forms of compound 1 for use in CNS disorders. The document defines crystalline Forms FUM-P3, FUM-P4, MLA-P3, MLA-P4, SUC-P3, and SUC-P4, each characterized by XRPD peak positions expressed as 2-theta angles.
The solid-state scope includes acid addition salts, co-crystals, and specified solid-state variants involving fumaric acid, L-malic acid, and succinate. For fumaric acid, the document includes fumarate and hemifumarate variants, including a co-crystal of compound 1 with fumaric acid, and related crystalline Forms FUM-P3 and FUM-P4. For L-malic acid, the document includes L-malate and mono-L-malate variants and corresponding crystalline Forms MLA-P3 and MLA-P4.
Crystalline form characterization is supported with thermal and spectroscopic analytical frameworks in addition to XRPD. The document describes that the crystalline forms can be identified or further validated by substantial similarity of DSC thermograms, DVS isotherms, TG-FTIR thermograms, and Raman spectra to depicted figures, and specifies substantially anhydrous, substantially free of impurities, or substantially free of amorphous compound 1.
Claims Coverage
The provided independent claims define crystalline forms of compound 1, including FUM-P3, FUM-P4, MLA-P3, MLA-P4, and in the provided portion FUM-P4 and MLA-P4. Across the families, inventive features are driven by XRPD peak-selection constraints and dependent-claim refinements that add thermal, Raman, and solid-state qualifiers.
Crystalline form FUM-P3 with selected XRPD peaks
A crystalline Form FUM-P3 of compound 1 characterized by having three or more peaks in its XRPD pattern selected from a table of 2-theta angles.
Crystalline form FUM-P4 with selected XRPD peaks
A crystalline Form FUM-P4 of compound 1 characterized by having three or more peaks in its XRPD pattern selected from a table of 2-theta angles.
Crystalline form MLA-P3 with selected XRPD peaks
A crystalline Form MLA-P3 of compound 1 characterized by having four or more peaks in its XRPD pattern selected from a table of 2-theta angles.
Crystalline form MLA-P4 with selected XRPD peaks
A crystalline Form MLA-P4 of compound 1 characterized by having four or more peaks in its XRPD pattern selected from a table of 2-theta angles.
Crystalline Form FUM-P4 Defined by Selected XRPD Peaks
A crystalline Form FUM-P4 of compound 1 wherein the crystalline Form FUM-P4 is characterized by having three or more peaks in its XRPD pattern selected from those in the following table at 2-Theta angles 17.64, 18.45, 20.10, 21.10, 21.53, 23.26, and 24.68.
Crystalline Form MLA-P4 Defined by Selected XRPD Peaks
A crystalline Form MLA-P4 of compound 1 wherein the crystalline Form MLA-P4 is characterized by having four or more peaks in its XRPD pattern selected from those in the following table at 2-Theta angles 5.33, 7.52, 8.40, 16.81, 18.81, 21.19, 22.63, and 24.24.
Overall, the claim coverage centers on crystalline forms of compound 1 defined by XRPD peak-selection criteria, with dependent claims further requiring XRPD and thermal correspondence to specific figures and, for FUM-P4, TG-FTIR and tetrahydrofuran-related qualifiers. The families also cover fumarate and hemifumarate variants, co-crystals with fumaric acid, L-malate and mono-L-malate variants, co-crystals with L-malic acid, and qualifiers such as substantially free of impurities and substantially free of amorphous compound 1.
Stated Advantages
Documented Applications
No documented applications found
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