1,4-disubstituted imidazole derivative
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.
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.