Inhibitors of EZH2

• US 9,527,837 B2
• Filed: 12/01/2015
• Issued: 12/27/2016
• Est. Priority Date: 12/05/2014
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Yu, Kuo-Long, Guo, Deqi
• Primary Examiner(s): Davis, Zinna Northington
• Application Number:
  US14/955,074
• Publication Number:
  US 20160159782A1
• Time in Patent Office: 392 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/14 containing three or more hetero rings

Abstract

The present invention relates to compounds that inhibit activity of the histone lysine N-methyltransferase, Enhancer of Zeste Homolog 2 (EZH2), pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat cancer, such as hematologic and solid tumors.

Claims

1. A compound selected from the group consisting of:

N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-{(1R)-1-[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]ethyl}-4-methylthiophene-3-carboxamide;

2. The compound according to claim 1 which is N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-{(1R)-1-[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]ethyl}-4-methylthiophene-3-carboxamide:

3. The compound according to claim 2 which is N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-{(1R)-1-[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]ethyl}-4-methylthiophene-3-carboxamide:

4. A pharmaceutical composition comprising a compound selected from the group consisting of:

N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-{(1R)-1-[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]ethyl}-4-methylthiophene-3-carboxamide;

5. A method of treating cancer, wherein the cancer is diffuse large B-cell lymphoma, comprising administering to a patient in need thereof, an effective amount of a compound selected from the group consisting of:

N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-{(1R)-1-[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]ethyl}-4-methylthiophene-3-carboxamide;