Imidazopyridinyl-benzamide anti-cancer agents
View Patent ↗Provided are compounds of Formula V and pharmaceutically acceptable salts thereof which may be useful for the treatment of cancer or other proliferative disorders.
1. A compound of Formula V
or a pharmaceutically acceptable salt thereof wherein
R 2 is hydrogen or lower alkyl;
R 3 is chosen from
lower alkyl substituted with a hydroxyl or a phosphate ester thereof and
lower alkyl substituted with an amino group wherein the amino group is further substituted with a group —COR b wherein R b is chosen from hydrogen, C 1 -C 6 alkyl, aryl, and heteroaryl;
R 11 is hydrogen, cyano, nitro, or halo;
R 12 is lower alkoxy or 2,2,2-trifluoro-1-methyl-ethoxy;
R 13 is hydrogen, alkyl-, alkoxy, halo, hydroxyl, nitro, cyano, or amino;
R 14 is imidazo[1,2-a]pyridin-2-yl optionally substituted with one or two groups chosen from lower alkyl, halo, acyl, trifluoromethyl, aminomethyl, and lower alkyl substituted with hydroxy; and
R 15 is chosen from hydrogen, halo, hydroxyl, and lower alkyl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 15 is hydrogen.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11 is chloro or cyano.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12 is propoxy or 2,2,2-trifluoro-1-methyl-ethoxy.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 13 is hydrogen.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen.
7. A composition comprising a pharmaceutical excipient and at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.
8. A compound of Formula V
or a pharmaceutically acceptable salt thereof wherein
R 2 is hydrogen or lower alkyl:
R 3 is —CH 2 CH 2 OH, —CH 2 NHC(O)CH 2 N(CH 3 ) 2 or —CH 2 NHC(O)C(CH 3 ) 2 NH 2
R 11 is hydrogen, cyano, nitro, or halo;
R 12 is lower alkoxy or 2,2,2-trifluoro-1-methyl-ethoxy;
R 13 is hydrogen, alkyl-, alkoxy, halo, hydroxyl, nitro, cyano, or amino;
R 14 is imidazo[1,2-a]pyridin-2-yl optionally substituted with one or two groups chosen from lower alkyl, halo, acyl, trifluoromethyl, aminomethyl, and lower alkyl substituted with hydroxy; and
R 15 is chosen from hydrogen, halo, hydroxyl, and lower alkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 14 is 8-methyl-imidazo[1,2-a]pyridin-2-yl, 8-ethyl-imidazo[1,2-a]pyridin-2-yl, 8-chloro-imidazo[1,2-a]pyridin-2-yl, 8-trifluoromethyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-acetyl-imidazo[1,2-a]pyridin-2-yl, 8-isopropyl-imidazo[1,2-a]pyridin-2-yl, 8-acetyl-5-methyl-imidazo[1,2-a]pyridin-2-yl, 8-hydroxymethyl-imidazo[1,2-a]pyridin-2-yl, 5-methyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-methyl-1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxypropyl)-imidazo[1,2-a]pyridin-2-yl, 8-(aminomethyl)imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-1-methylethyl)imidazo[1,2-a]pyridin-2-yl, 8-[(1R)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, 8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, 3-fluoro-8-methylimidazo[1,2-a]pyridin-2-yl, 8-ethyl-5-methylimidazo[1,2-a]pyridin-2-yl, or 3-chloro-8-methylimidazo[1,2-a]pyridin-2-yl.
10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 14 is 8-methyl-imidazo[1,2-a]pyridin-2-yl, 8-ethyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-hydroxymethyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-methyl-1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxypropyl)-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-1-methylethyl)imidazo[1,2-a]pyridin-2-yl, 8-[(1R)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, or 8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl.
11. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 15 is hydrogen.
12. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 11 is chloro or cyano.
13. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 12 is propoxy or 2,2,2-trifluoro-1-methyl-ethoxy.
14. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 13 is hydrogen.
15. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen.
16. A composition comprising a pharmaceutical excipient and at least one compound of claim 8 , or a pharmaceutically acceptable salt thereof.
17. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 14 is 8-methyl-imidazo[1,2-a]pyridin-2-yl, 8-ethyl-imidazo[1,2-a]pyridin-2-yl, 8-chloro-imidazo[1,2-a]pyridin-2-yl, 8-trifluoromethyl-imidazo[1,2-a]pyridin-2-yl, 8-( 1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-acetyl-imidazo[1,2-a]pyridin-2-yl, 8-isopropyl-imidazo[1,2-a]pyridin-2-yl, 8-acetyl-5-methyl-imidazo[1,2-a]pyridin-2-yl, 8-hydroxymethyl-imidazo[1,2-a]pyridin-2-yl, 5-methyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-methyl-1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxypropyl)-imidazo[1,2-a]pyridin-2-yl, 8-(aminomethyl)imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-1-methylethyl)imidazo[1,2-a]pyridin-2-yl, 8-[(1R)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, 8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, 3-fluoro-8-methylimidazo[1,2-a]pyridin-2-yl, 8-ethyl-5-methylimidazo[1,2-a]pyridin-2-yl, or 3-chloro-8-methylimidazo[1,2-a]pyridin-2-yl.
18. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 14 is 8-methyl-imidazo[1,2-a]pyridin-2-yl, 8-ethyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-hydroxymethyl-imidazo[1,2-a]pyridin-2-yl, 8-(1-methyl-1-hydroxy-ethyl)-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxypropyl)-imidazo[1,2-a]pyridin-2-yl, 8-(1-hydroxy-1-methylethyl)imidazo[1,2-a]pyridin-2-yl, 8-[(1R)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl, or 8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl.