1,4-disubstituted imidazole derivative

Patent metadata

Field	Value
Publication number	US-2017166552-A1
Application number	US-201715443892-A
Country	US
Kind code	A1
Filing date	Feb 27, 2017
Priority date	Jun 22, 2015
Publication date	Jun 15, 2017
Grant date	—

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

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-imidazol-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 for treating cancer 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]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]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.

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

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

Classifications

• C07D403/12

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

• C07D401/12 Primary

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

• C07D417/12

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

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title