Cocrystal

Patent metadata

Field	Value
Publication number	US-10906898-B2
Application number	US-201716074339-A
Country	US
Kind code	B2
Filing date	Jan 31, 2017
Priority date	Feb 1, 2016
Publication date	Feb 2, 2021
Grant date	Feb 2, 2021

Abstract

Improving the solubility of an organic compound. A cocrystal of (1) 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide and (2) L-malic acid or L-tartaric acid.

First claim

The invention claimed is:

1. A cocrystal of
(1) 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide and
(2) L-malic acid or L-tartaric acid.

2. The cocrystal according to claim 1 that is a cocrystal of
(1) 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide and
(2) L-malic acid.

3. The cocrystal according to claim 2 , characterized by a powder X-ray diffraction pattern comprising characteristic peaks at d values of 11.7±0.2, 10.0±0.2, and 8.6±0.2 angstroms.

4. The cocrystal according to claim 1 that is a cocrystal of
(1) 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide and
(2) L-tartaric acid.

5. The cocrystal according to claim 4 , characterized by a powder X-ray diffraction pattern comprising characteristic peaks at d values of 12.0±0.2, 10.1±0.2 and 8.7±0.2 angstroms.

6. A pharmaceutical composition comprising the cocrystal according to claim 1 .

7. The pharmaceutical composition according to claim 6 that is a Smo inhibitor.

8. The pharmaceutical composition according to claim 6 that is a prophylactic and/or therapeutic agent for cancer.

9. A method for inhibiting Smo in a mammal, comprising administering an effective amount of the cocrystal according to claim 1 to the mammal.

10. A method for treating cancer in a mammal, comprising administering an effective amount of the cocrystal according to claim 1 to the mammal.

11. The method according to claim 10 , wherein the cancer is selected from one or more of colorectal cancer, lung cancer, mesothelioma, pancreatic cancer, pharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, duodenal cancer, small intestinal cancer, breast cancer, ovarian cancer, testicular cancer, prostate cancer, liver cancer, thyroid cancer, kidney cancer, uterus cancer, brain tumor, retinoblastoma, skin cancer, sarcoma, malignant bone tumor, urinary bladder cancer, and blood cancer.

12. The method of claim 10 , wherein the cancer is selected from one or more of glioma, medulloblastoma, basal cell tumor, small cell lung cancer, pancreatic cancer, cancer of the bile duct, prostate cancer, esophagus cancer, gastric cancer, colorectal cancer, rhabdomyosarcoma, and breast cancer.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Iwata Kentaro
• Ikeda Yukihiro

Classifications

• A61K31/4545 Primary

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07C59/255

  Tartaric acid · CPC title

• C07C59/245

  containing hydroxy or O-metal groups · CPC title