Preparation of and formulation comprising a mek inhibitor

Patent metadata

Field	Value
Publication number	US-2016168104-A1
Application number	US-201615053441-A
Country	US
Kind code	A1
Filing date	Feb 25, 2016
Priority date	Oct 19, 2012
Publication date	Jun 16, 2016
Grant date	—

Abstract

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro -3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.

First claim

1 . (canceled)

2 . A method of treating a proliferative disease in a patient in need thereof, comprising administering to said mammal a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient.

3 . The method according to claim 2 , wherein the proliferative disease is cancer.

4 . The method according to claim 3 , wherein the cancer is selected from melanoma, pancreatic cancer, ovarian cancer, carcinoma of the fallopian tubes, peritoneal cancer, biliary cancer, colon cancer, or rectal cancer.

5 . The method according to claim 4 , wherein the cancer is melanoma.

6 . The method according to claim 5 , wherein said melanoma is BRAFV600 or NRAS-mutant melanoma.

7 . The method according to claim 6 , wherein the pharmaceutical composition is formulated as a tablet.

8 . The method according to claim 7 , wherein the pharmaceutical composition comprises approximately 15 mg crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.

9 . The method according to claim 8 , wherein the pharmaceutical composition further comprises lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, and magnesium stearate.

10 . The method according to claim 9 , wherein said melanoma is NRAS-mutant melanoma.

11 . The method according to claim 6 , further comprising administering an additional therapeutic agent.

12 . The method according to claim 11 , wherein the additional therapeutic agent is a chemotherapeutic agent or anti-tumor agent.

13 . The method according to claim 12 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered separately.

14 . The method according to claim 13 , wherein said melanoma is BRAFV600 mutant melanoma.

15 . The method according to claim 12 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered simultaneously.

16 . The method according to claim 4 , wherein the cancer is colon cancer.

17 . The method according to claim 4 , wherein the cancer is ovarian cancer.

Assignees

• Novartis Pharma Ag
• Array Biopharma Inc

Inventors

• Krell Christoph Max
• Misun Marian
• Niederer Daniel Andreas
• Pachinger Werner Heinz
• Wolf Marie-Christine
• Zimmermann Daniel
• Liu Weidong
• Stengel Peter J
• Nichols Paul

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title