Voruciclib polymorphs and methods of making and using thereof

Patent metadata

Field	Value
Publication number	US-2023167096-A1
Application number	US-202017602935-A
Country	US
Kind code	A1
Filing date	Apr 11, 2020
Priority date	Apr 11, 2019
Publication date	Jun 1, 2023
Grant date	—

Abstract

The disclosure relates to crystalline solid forms of voruciclib, including voruciclib free base and various voruciclib salts, pharmaceutical compositions containing voruciclib crystalline solid forms, and methods for treating conditions or disorders by administering pharmaceutical compositions including voruciclib crystalline solid forms.

First claim

1 . A crystal form of voruciclib, comprising voruciclib free base or a voruciclib salt comprising a counterion corresponding to an acid selected from 1,5-naphthalenedisulfonic acid, 1-hydroxy-2-naphthoic acid, benzenesulfonic acid, benzoic acid, dibenzoyl-L-tartaric acid, ethanesulfonic acid, gentisic acid, hydrobromic acid, hydrochloric acid, maleic acid, malonic acid, oxalic acid, ortho-phosphoric acid, sulfuric acid, and p-toluenesulfonic acid.

2 . The crystal form of voruciclib of claim 1 , characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 7.30°±0.2°, 13.58°±0.2°, 14.06°±0.2°, 15.18°±0.2°, 15.66°±0.2°, 17.50°±0.2°, 18.94°±0.2°, 19.54°±0.2°, 22.22°±0.2°, 23.38°±0.2°, 24.10°±0.2°, 24.98°±0.2°, 25.94°±0.2°, 27.26°±0.2°, 28.50°±0.2°, and 32.82°±0.2° 2θ.

3 . The crystal form of claim 2 , wherein the crystal form comprises voruciclib malonate.

4 . The crystal form of voruciclib of claim 1 , characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 5.06°±0.2°, 6.42°±0.2°, 9.34°±0.2°, 10.14°±0.2°, 12.30°±0.2°, 13.66°±0.2°, 14.14°±0.2°, 15.82°±0.2°, 17.02°±0.2°, 19.74°±0.2°, 20.38°±0.2°, 21.82°±0.2°, 22.66°±0.2°, 24.62°±0.2°, 25.78°±0.2°, 26.58°±0.2°, 28.66°±0.2°, and 29.98°±0.2° 2θ.

5 . The crystal form of claim 4 , wherein the crystal form comprises voruciclib dibenzoyl-tartrate.

6 . The crystal form of voruciclib of claim 1 , characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 4.94°±0.2°, 6.78°±0.2°, 9.34°±0.2°, 10.94°±0.2°, 12.70°±0.2°, 13.38°±0.2°, 14.90°±0.2°, 15.66°±0.2°, 17.54°±0.2°, 18.82°±0.2°, 22.02°±0.2°, 23.98°±0.2°, 24.78°±0.2°, 25.30°±0.2°, 26.66°±0.2°, and 29.98°±0.2° 2θ.

7 . The crystal form of claim 6 , wherein the crystal form comprises voruciclib phosphate.

8 . The crystal form of voruciclib of claim 1 , characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 6.86°±0.2°, 12.66°±0.2°, 13.58°±0.2°, 14.74°±0.2°, 15.98°±0.2°, 19.38°±0.2°, 23.94°±0.2°, 24.78°±0.2°, and 25.94°±0.2° 2θ.

9 . The crystal form of claim 8 , wherein the crystal form comprises voruciclib oxalate.

10 . The crystal form of voruciclib of claim 1 , characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 9.02°±0.2°, 10.50°±0.2°, 11.06°±0.2°, 12.30°±0.2°, 12.82°±0.2°, 13.90°±0.2°, 14.82°±0.2°, 15.30°±0.2°, 15.94°±0.2°, 17.26°±0.2°, 19.34°±0.2°, 20.62°±0.2°, 22.18°±0.2°, 22.86°±0.2°, 24.58°±0.2°, 25.42°±0.2°, 25.86°±0.2°, 27.38°±0.2°, and 28.66°±0.2° 2θ.

11 . The crystal form of claim 10 , wherein the crystal form comprises voruciclib napadisylate.

12 . The crystal form of claim 1 , wherein the crystal form is a crystalline anhydrate.

13 . The crystal form of claim 1 , wherein the crystal form is a crystalline hydrate.

14 . A crystal form of voruciclib malonate characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 6.36°±0.2° 2θ, 13.88°±0.2° 2θ, 7.31°±0.2° 2θ, 9.34°±0.2° 2θ, 10.05°±0.2° 2θ, 13.59°±0.2° 2θ, 14.08°±0.2° 2θ, 15.21°±0.2° 2θ, 15.67°±0.2° 2θ, 17.53°±0.2° 2θ, 18.70°±0.2° 2θ, 18.98°±0.2° 2θ, 19.38°±0.2° 2θ, 19.67°±0.2° 2θ, 20.16°±0.2° 2θ, 20.39°±0.2° 2θ, 21.01°±0.2° 2θ, 22.27°±0.2° 2θ, 23.35°±0.2° 2θ, 24.15°±0.2° 2θ, 24.67°±0.2° 2θ, 25.00°±0.2° 2θ, 25.18°±0.2° 2θ, 25.57°±0.2° 2θ, 25.93°±0.2° 2θ, 26.21°±0.2° 2θ, 27.19°±0.2° 2θ, and 27.38°±0.2° 2θ.

15 . A crystal form of voruciclib oxalate characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 6.86°±0.2° 2θ, 9.70°±0.2° 2θ, 10.84°±0.2° 2θ, 12.50°±0.2° 2θ, 12.66°±0.2° 2θ, 12.81°±0.2° 2θ, 13.41°±0.2° 2θ, 13.71°±0.2° 2θ, 14.54°±0.2° 2θ, 15.35°±0.2° 2θ, 15.83°±0.2° 2θ, 18.70°±0.2° 2θ, 19.00°±0.2° 2θ, 19.43°±0.2° 2θ, 19.62°±0.2° 2θ, 21.75°±0.2° 2θ, 22.75°±0.2° 2θ, 23.35°±0.2° 2θ, 23.47°±0.2° 2θ, 23.81°±0.2° 2θ, 23.98°±0.2° 2θ, 24.36°±0.2° 2θ, 24.60°±0.2° 2θ, 24.86°±0.2° 2θ, 25.11°±0.2° 2θ, 25.60°±0.2° 2θ, 25.75°±0.2° 2θ, and 26.25°±0.2° 2θ.

16 . A crystal form of voruciclib phosphate characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 4.93°±0.2° 2θ, 6.79°±0.2° 2θ, 9.35°±0.2° 2θ, 10.58°±0.2° 2θ, 10.91°±0.2° 2θ, 12.64°±0.2° 2θ, 13.35°±0.2° 2θ, 13.58°±0.2° 2θ, 14.81°±0.2° 2θ, 15.60°±0.2° 2θ, 17.18°±0.2° 2θ, 17.52°±0.2° 2θ, 18.32°±0.2° 2θ, 18.78°±0.2° 2θ, 19.34°±0.2° 2θ, 19.64°±0.2° 2θ, 19.78°±0.2° 2θ, 22.02°±0.2° 2θ, 23.20°±0.2° 2θ, 23.67°±0.2° 2θ, 24.00°±0.2° 2θ, 24.71°±0.2° 2θ, 25.21°±0.2° 2θ, 25.39°±0.2° 2θ, 26.55°±0.2° 2θ, 27.22°±0.2° 2θ, 28.07°±0.2° 2θ, and 29.90°±0.2° 2θ.

17 - 18 . (canceled)

19 . A method of treating a disease in a patient, the method comprising administering to the patient a therapeutically effective amount of the crystal form of voruciclib of claim 1 , wherein the disease is selected from the group consisting of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, B-cell lymphoproliferative disease, B cell acute lymphoblastic leukemia, Waldenström's macroglobulinemia, Burkitt's leukemia, Hodgkin's disease, multiple myeloma, acute myeloid leukemia, juvenile myelomonocytic leukemia, hairy cell leukemia, mast cell leukemia, mastocytosis, myeloproliferative disorders (MPDs), myeloproliferative neoplasms, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), myelodysplastic syndrome, chronic myelogenous leukemia (BCR-ABL1-positive), chronic neutrophilic leukemia, chronic eosinophilic leukemia, primary central nervous system (CNS) lymphoma, primary multifocal lymphoma of peripheral nervous system (PNS), thymus cancer, brain cancer, glioblastoma, lung cancer, squamous cell cancer, skin cancer (e.g., melanoma), eye cancer, retinoblastoma, intraocular melanoma, oral cavity and oropharyngeal cancers, bladder cancer, gastric cancer, stomach cancer, pancreatic cancer, breast cancer, cervical cancer, head and neck cancer, renal cancer, kidney cancer, liver cancer, ovarian cancer, prostate cancer, colorectal cancer, bone cancer (e.g., metastatic bone cancer), esophageal cancer, testicular cancer, gynecological cancer, thyroid cancer, epidermoid cancer, AIDS-related cancer (e.g., lymphoma), viral-induced cervical carcinoma (human papillomavirus), nasopharyngeal carcinoma (Epstein-Barr virus), Kaposi's sarcoma, primary effusion lymphoma (Kaposi's sarcoma herpesvirus), hepatocellular carcinoma (hepatitis B and hepatitis C viruses), T-cell leukemias (Human T-cell leukemia virus-1), benign hyperplasia of the skin, restenosis, benign prostatic hypertrophy, tumor angiogenesis, chronic inflammatory disease, rheumatoid arthritis, atherosclerosis, inflammatory bowel disease, skin diseases such as psoriasis, eczema, and scleroderma, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, ulcerative colitis, atopic dermatitis, pouchitis, spondylarthritis, uveitis, Behcet's disease, polymyalgia rheumatica, giant-cell arteritis, sarcoidosis, Kawasaki disease, juvenile idiopathic arthritis, hidratenitis suppurativa, Sjögren's syndrome, psoriatic arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, lupus, and lupus nephritis.

20 . A method of treating a hyperproliferative disease in a patient, the method comprising administering to the patient a therapeutically effective amount of the crystal form of voruciclib of claim 1 , wherein the hyperproliferative disease is selected from the group consisting of acute lymph

Assignees

• Mei Pharma Inc

Inventors

• Duncan David Frank

Classifications

• A61K31/4025

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

• A61P35/02

  specific for leukemia · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D405/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title