1,4-disubstituted imidazole derivative

Patent metadata

Field	Value
Publication number	US-9828362-B2
Application number	US-201715443892-A
Country	US
Kind code	B2
Filing date	Feb 27, 2017
Priority date	Jun 22, 2015
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The present invention provides a 1,4-disubstituted imidazole derivative of formula (1′) wherein ring Q 1 is optionally-substituted C 6-10 aryl group, etc.; R 1 and R 2 are independently hydrogen atom, etc.; W 1 is optionally-substituted C 1-4 alkylene group; W 2 is —NR 3a C(O)— wherein R 3a is hydrogen atom or C 1-6 alkyl group, etc.; ring Q 2 is 5- to 10-membered heteroaryl group, etc.; W 3 is optionally-substituted C 1-4 alkylene group, etc.; n is 1, 2, 3, 4, or 5; R 4 is independently halogen atom, optionally-substituted C 1-6 alkyl group, etc.; R 5 is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:
5-(difluoromethyl)-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide;
5-(difluoromethyl)-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide;
6-(hydroxymethyl)-5-methyl-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide;
5-amino-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide; and
5-amino-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazo1-4-yl]nicotinamide,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein the compound is 5-(difluoromethyl)-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein the compound is 5-(difluoromethyl)-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 wherein. the compound is 6-(hydroxymethyl)-5-methyl-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 wherein the compound is 5-amino-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 wherein the compound is 5-amino-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

7. A method treating cancer which comprises administering a therapeutically effective amount of compound selected from the group consisting of:
5-(difluoromethyl)-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide;
5-(difluoromethyl)-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide;
6-(hydroxymethyl)-5-methyl-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide;
5-amino-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide; and
5-amino-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide,

or a pharmaceutically acceptable salt thereof to a patient in need thereof.

8. The method of claim 7 wherein the compound is 5-(difluoromethyl)-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide, or a pharmaceutically acceptable salt thereof.

9. The method of claim 7 wherein the compound is 5-(difluoromethyl)-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

10. The method of claim 7 wherein the compound is 6-(hydroxymethyl)-5-methyl-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

11. The method of claim 7 wherein the compound is 5-amino -6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide, or a pharmaceutically acceptable salt thereof.

12. The method of claim 7 wherein the compound is 5-amino-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide, or a pharmaceutically acceptable salt thereof.

13. The method of claim 7 which comprises inhibiting the sphere-forming ability of cancer cells.

14. A method for inhibiting the sphere-forming ability of cancer cells, which comprises administering a therapeutically effective amount of a compound selected from the group consisting of:
5-(difluoromethyl)-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide;
5-(difluoromethyl)-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide;
6-(hydroxymethyl)-5-methyl-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicatinamide;
5-amino-6-(hydroxymethyl)-N-{1-[3-(trifluoromethyl)benzyl]-1H-imidazol-4-yl}nicotinamide; and
5-amino-6-(hydroxymethyl)-N-[1-(3,4,5-trifluorobenzyl)-1H-imidazol-4-yl]nicotinamide,

or a pharmaceutically acceptable salt thereof to a patient in need thereof.

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Ban Hitoshi
• Kusagi Manabu
• Tojo Shingo
• Hasegawa Futoshi
• Hashizume Miki

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title