Solid forms of a compound for modulating kinases

Patent metadata

Field	Value
Publication number	US-2020299293-A1
Application number	US-202016894683-A
Country	US
Kind code	A1
Filing date	Jun 5, 2020
Priority date	Oct 13, 2017
Publication date	Sep 24, 2020
Grant date	—

Abstract

Forms of 4-(6-(3,5-dimethylisoxazol-4-yl)-1-[(1S)-1-(2-pyridyl)ethyl]pyrrolo[3,2-b]pyridin-3-yl)benzoic acid (Compound I) were prepared and characterized in the solid state:

Also provided are processes of manufacture and methods of using the forms of Compound I.

First claim

What is claimed is:

1 . A crystalline form of Compound I:

characterized by an X-ray powder diffractogram comprising peaks (±0.2°) at 3.5, 18.0, and 19.1 °2θ as determined on a diffractometer using Cu-Ka radiation.

2 . The crystalline form of Compound I according to claim 1 , wherein the diffractogram further comprises one or more peaks (±0.2°) at 7.0, 10.8, 11.4, 13.1, 15.5, 17.4, 17.5, 18.5, 19.7, and 21.2 °2θ as determined on a diffractometer using Cu-Ka radiation.

3 . The crystalline form of Compound I according to claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm with a peak maximum at about 235.0° C.

4 . The crystalline form of Compound I according to claim 1 , comprising an X-ray powder diffractogram substantially as shown in FIG. 11 .

5 . The crystalline form of Compound I according to claim 1 , comprising a thermogram substantially as shown in FIG. 12 .

6 . A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, and the crystalline form of Compound I according to claim 1 .

7 . A method for treating a subject suffering from, or at risk of, a disease or condition mediated by a bromodomain, the method comprising administering to the subject in need thereof an effective amount of the crystalline form of Compound I according to claim 1 , wherein the disease or condition is myelodysplastic syndromes (MDS), rheumatoid arthritis, uveal melanoma, chronic lymphocytic leukemia, acute myeloid leukemia, synovial sarcoma, osteoarthritis, acute gout, psoriasis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease (Crohn's disease and Ulcerative colitis), asthma, chronic obstructive airways disease, pneumonitis, myocarditis, pericarditis, myositis, eczema, dermatitis, alopecia, vitiligo, bullous skin diseases, nephritis, vasculitis, atherosclerosis, Alzheimer's disease, depression, retinitis, uveitis, scleritis, hepatitis, pancreatitis, primary biliary cirrhosis, sclerosing cholangitis, Addison's disease, hypophysitis, thyroiditis, type I diabetes, or acute rejection of transplanted organs.

8 . A method of treating chronic lymphocytic leukemia (CLL) or Richter's Syndrome in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of a Bruton's Tyrosine Kinase (BTK) inhibitor.

9 . The method of claim 8 , wherein the BTK inhibitor is ibrutinib.

10 . A method of treating chronic lymphocytic leukemia (CLL) in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of a B-cell lymphoma 2 (BCL-2) inhibitor.

11 . The method of claim 10 , wherein the BCL-2 inhibitor is venetoclax.

12 . A method of treating uveal melanoma in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of a CTLA-4 inhibitor or a checkpoint inhibitor.

13 . A method of treating acute myeloid leukemia in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of quizartinib.

14 . A method of treating acute myeloid leukemia in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of azacitidine.

15 . A method of treating myelodysplastic syndromes (MDS) in a subject in need thereof by administering to the subject an effective amount of the crystalline form of Compound I according to claim 1 , in combination with an effective amount of azacitidine.

Assignees

• Plexxikon Inc

Inventors

• Ibrahim Prabha N
• Rezaei Hamid
• Nespi Marika
• Powell Ben
• Patel Rashmin

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title