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CN-122029165-A - SAMURACICLIB solid state forms

CN122029165ACN 122029165 ACN122029165 ACN 122029165ACN-122029165-A

Abstract

The present disclosure encompasses solid state forms of Samuraciclib and/or Samuraciclib salts, in embodiments encompasses crystalline polymorphs of Samuraciclib and/or Samuraciclib salts, processes for their preparation, and pharmaceutical compositions thereof.

Inventors

  • Lorena Kodick

Assignees

  • 阿西亚化学工业有限公司

Dates

Publication Date
20260512
Application Date
20240911
Priority Date
20230911

Claims (20)

  1. 1. Crystallization Samuraciclib.
  2. 2. A crystalline form designated form B1, samuraciclib, characterized by data selected from the group consisting of: (a) An X-ray powder diffraction pattern substantially in accordance with that depicted in figure 1; (b) An X-ray powder diffraction pattern having peaks at 7.6 degrees 2 theta + 0.2 degrees 2 theta, 9.4 degrees 2 theta + 0.2 degrees 2 theta, 12.7 degrees 2 theta + 0.2 degrees 2 theta, 19.0 degrees 2 theta + 0.2 degrees 2 theta, and 20.2 degrees 2 theta + 0.2 degrees 2 theta; and combinations of these data.
  3. 3. The crystal Samuraciclib according to claim 2, which is further characterized by an X-ray powder diffraction pattern having any one, two, three, four, or five additional peaks selected from 11.8 degrees 2Θ ± 0.2 degrees 2Θ, 16.2 degrees 2Θ ± 0.2 degrees 2Θ, 16.9 degrees 2Θ ± 0.2 degrees 2Θ, 17.3 degrees 2Θ ± 0.2 degrees 2Θ, and 21.2 degrees 2Θ ± 0.2 degrees 2Θ.
  4. 4. The crystal Samuraciclib of claim 2 or 3, characterized by an XRPD pattern having peaks at 7.6 degrees 2Θ ± 0.2 degrees 2Θ, 9.4 degrees 2Θ ± 0.2 degrees 2Θ, 11.8 degrees 2Θ ± 0.2 degrees 2Θ, 12.7 degrees 2Θ ± 0.2 degrees 2Θ, 16.2 degrees 2Θ ± 0.2 degrees 2Θ, 16.9 degrees 2Θ ± 0.2 degrees 2Θ, 17.3 degrees 2Θ ± 0.2 degrees 2Θ, 19.0 degrees 2Θ ± 0.2 degrees 2Θ, 20.2 degrees 2Θ ± 0.2 degrees 2Θ, and 21.2 degrees 2Θ ± 0.2 degrees 2Θ.
  5. 5. The crystal Samuraciclib of any one of claims 2, 3, or 4, which is substantially free of any other solid-state form of Samuraciclib.
  6. 6. A crystalline form designated form B2, samuraciclib, characterized by data selected from the group consisting of: (a) An X-ray powder diffraction pattern substantially in accordance with that depicted in fig. 5; (b) An X-ray powder diffraction pattern having peaks at 10.0 degrees 2 theta + 0.2 degrees 2 theta, 18.0 degrees 2 theta + 0.2 degrees 2 theta, and 24.6 degrees 2 theta + 0.2 degrees 2 theta; and combinations of these data.
  7. 7. The crystal Samuraciclib of claim 6, further characterized by an X-ray powder diffraction pattern having any one, two, or three additional peaks selected from the group consisting of 6.7 degrees 2Θ ± 0.2 degrees 2Θ, 12.3 degrees 2Θ ± 0.2 degrees 2Θ, and 17.1 degrees 2Θ ± 0.2 degrees 2Θ.
  8. 8. The crystal Samuraciclib of claim 6 or 7, which is characterized by an XRPD pattern having peaks at 6.7 degrees 2Θ ± 0.2 degrees 2Θ, 10.0 degrees 2Θ ± 0.2 degrees 2Θ, 12.3 degrees 2Θ ± 0.2 degrees 2Θ, 17.1 degrees 2Θ ± 0.2 degrees 2Θ, 18.0 degrees 2Θ ± 0.2 degrees 2Θ, and 24.6 degrees 2Θ ± 0.2 degrees 2Θ.
  9. 9. The crystal Samuraciclib of any one of claims 6,7, or 8, which is substantially free of any other solid-state form of Samuraciclib.
  10. 10. Crystallization Samuraciclib dihydrochloride.
  11. 11. A crystalline form of Samuraciclib dihydrochloride designated form H4, said crystalline form characterized by data selected from the group consisting of: (a) An X-ray powder diffraction pattern substantially in accordance with that depicted in fig. 4; (b) An X-ray powder diffraction pattern having peaks at 7.3 degrees 2 theta +0.2 degrees 2 theta, 15.0 degrees 2 theta +0.2 degrees 2 theta, and 23.1 degrees 2 theta +0.2 degrees 2 theta; and combinations of these data.
  12. 12. The crystalline Samuraciclib dihydrochloride salt according to claim 11, further characterized by an X-ray powder diffraction pattern having any one, two or three additional peaks selected from 8.1 degrees 2Θ ± 0.2 degrees 2Θ, 15.4 degrees 2Θ ± 0.2 degrees 2Θ, and 21.8 degrees 2Θ ± 0.2 degrees 2Θ.
  13. 13. The crystalline Samuraciclib dihydrochloride salt of claim 11 or 12, characterized by an XRPD pattern having peaks at 7.3 degrees 2Θ ± 0.2 degrees 2Θ, 8.1 degrees 2Θ ± 0.2 degrees 2Θ, 15.0 degrees 2Θ ± 0.2 degrees 2Θ, 15.4 degrees 2Θ ± 0.2 degrees 2Θ, 21.8 degrees 2Θ ± 0.2 degrees 2Θ, and 23.1 degrees 2Θ ± 0.2 degrees 2Θ.
  14. 14. The crystal Samuraciclib of any one of claims 11, 12, or 13, which is substantially free of any other solid state form of Samuraciclib or Samuraciclib hydrochloride.
  15. 15. Use of crystalline Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1 to 14 for the preparation of a pharmaceutical composition of a Samuraciclib or Samuraciclib salt.
  16. 16. A pharmaceutical composition comprising the crystalline Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1 to 14, and at least one pharmaceutically acceptable excipient.
  17. 17. Use of Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1 to 14 for the preparation of a pharmaceutical composition and/or formulation.
  18. 18. A process for preparing a pharmaceutical composition according to claim 16, comprising combining the crystalline Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1-14 with at least one pharmaceutically acceptable excipient.
  19. 19. The crystalline Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1 to 14, or the pharmaceutical composition according to claim 16, for use as a medicament.
  20. 20. The crystalline Samuraciclib or Samuraciclib dihydrochloride according to any one of claims 1 to 14, or the pharmaceutical composition according to claim 16, for use as a medicament for the treatment of cancer, preferably breast cancer.

Description

SAMURACICLIB solid state forms Cross Reference to Related Applications The present application claims the benefit and priority of U.S. provisional patent application Ser. No. 63/581,730 filed on 9/month 11 of 2023, U.S. provisional patent application Ser. No. 63/590,801 filed on 10/month 17 of 2023, U.S. provisional patent application Ser. No. 63/599,586 filed on 11/month 16 of 2023, and U.S. provisional patent application Ser. No. 63/618,962 filed on 1/month 9 of 2024. The entire contents of the foregoing application are incorporated herein by reference. Field of the disclosure The present disclosure encompasses solid state forms of Samuraciclib and/or Samuraciclib salts, in embodiments encompasses crystalline polymorphs of Samuraciclib and/or Samuraciclib salts, processes for their preparation, and pharmaceutical compositions thereof. Background of the disclosure Samuraciclib, (3R, 4R) -4- [ [ [7- (benzylamino) -3-prop-2-ylpyrazolo [1,5-a ] pyrimidin-5-yl ] amino ] methyl ] piperidin-3-ol having the following chemical structure: 。 Samuraciclib is an orally available selective inhibitor of cyclin-dependent kinase 7 (CDK 7) with potential anti-tumour activity and is currently in clinical trials for the treatment of breast cancer. This compound is described in International publication No. WO 2015/124941. Polymorphism, i.e., the appearance of different crystalline forms (CRYSTALLINE FORM), is a property of some molecules and molecular complexes. A single molecule can produce multiple polymorphs having different crystal structures and physical properties such as melting point, thermal behavior (e.g., as measured by thermogravimetric analysis ("TGA") or differential scanning calorimetry ("DSC"), X-ray diffraction (XRD) patterns, infrared absorption fingerprint (infrared absorption fingerprint), and solid state (13 C) NMR spectra. One or more of these techniques may be used to distinguish between different polymorphic forms of a compound. Different salts and solid state forms (including solvated forms) of the active pharmaceutical ingredient may have different properties. Such changes in the nature of the different salts and solid state forms, as well as solvates, may provide a basis for improving the formulation, for example by promoting better processing or handling characteristics, changing the dissolution profile in a favorable direction, or improving stability (polymorphs and chemical stability) and shelf life. These variations in the nature of the different salts and solid state forms may also provide improvements to the final dosage form, for example, if they are used to improve bioavailability. Different salts and solid state forms as well as solvates of the active pharmaceutical ingredient may also produce multiple polymorphs or crystalline forms, which in turn may provide additional opportunities to evaluate changes in the nature and characteristics of the solid active pharmaceutical ingredient. The discovery of new solid state forms and solvates of pharmaceutical products can yield materials having desirable processing properties such as ease of handling, ease of processing, storage stability and ease of purification or as desirable intermediate crystalline forms that facilitate conversion to other polymorphic forms. New solid state forms of pharmaceutically useful compounds may also provide opportunities for improving the performance characteristics of pharmaceutical products. It expands the reservoirs of materials that formulation scientists can use to optimize, for example, by providing products with different properties, including different crystal habits, higher crystallinity or polymorphic stability, which can provide better processing or handling characteristics, improved dissolution profile, or improved shelf life (chemical/physical stability). For at least these reasons, there is a need for additional solid state forms (including solvated forms) of Samuraciclib and/or Samuraciclib salts. Summary of the disclosure The present disclosure provides crystalline polymorphs of Samuraciclib and/or Samuraciclib salts, and in embodiments, crystalline polymorphs of Samuraciclib and/or Samuraciclib salts, processes for their preparation, and pharmaceutical compositions thereof. These crystalline forms may be used to prepare Samuraciclib and other solid state forms of salts thereof. The present disclosure also provides for the use of the solid state forms of Samuraciclib and/or Samuraciclib salts in the preparation of Samuraciclib or other solid state forms of salts and/or co-crystals thereof. The present disclosure provides such crystalline forms of Samuraciclib and/or Samuraciclib salts for use in medicine, including for the treatment of cancer, particularly breast cancer. The present disclosure also encompasses the use of the crystalline polymorphs of Samuraciclib and/or Samuraciclib salts for the preparation of pharmaceutical compositions and/or formulations. In another aspect, the present disclosure