Imidazoyl-benzamide anti-cancer agents
View Patent ↗Provided are compounds of Formula I and pharmaceutically acceptable salts thereof which may be useful for the treatment of cancer or other proliferative disorders.
1. A compound of Formula I
or a pharmaceutically acceptable salt thereof, wherein
R 1 is chosen from 3-halo-4-((R)-1,1,1-trifluoropropan-2-yloxy)phenyl, 3-cyano-4-((R)-1,1,1-trifluoropropan-2-yloxy)phenyl, 3-halo-4-isopropylamino-phenyl, 3-cyano-4-isopropylamino-phenyl, 3-halo-4-((R)-1,1,1-trifluoropropan-2-ylamino)phenyl, and 3-cyano-4-((R)-1,1,1-trifluoropropan-2-ylamino)phenyl,
X is —CO,
R 2 is chosen from hydrogen and lower alkyl,
R 6 is phenyl substituted with R 14 at the para position and further substituted with a group R 15 wherein
R 14 is chosen from 1H-imidazol-2-yl, and 1H-imidazol-4-yl, each of which is optionally substituted with one or two groups chosen from halo, acyl, lower alkyl, and lower alkyl substituted with hydroxy; and
R 15 is chosen from hydrogen, halo, hydroxy, and lower alkyl
R 5 is hydrogen,
W is CH, and
R 3 is —CH 2 NH(CO)R 9 wherein R 9 is lower alkyl substituted with azetidino.
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 2 is hydrogen.
4. A composition comprising a pharmaceutical excipient and at least one compound of claim 1 or a pharmaceutically acceptable salt thereof.
5. A compound chosen from
N-((S)-1-(4-(2-acetyl-1-ethyl-1H-imidazol-4-yl)phenyl)-3-(2-(azetidin-1-yl)acetamido)propan-2-yl)-3-chloro-4-((R)-1,1,1-trifluoropropan-2-yloxy)benzamide;
N-((S)-1-(2-(azetidin-1-yl)acetamido)-3-(4-(2-(2-hydroxypropan-2-yl)-1-methyl-1H-imidazol-4-yl)phenyl)propan-2-yl)-3-chloro-4-((R)-1,1,1-trifluoropropan- 2-yloxy)benzamide;
N-(2-{[4-((1R)-2,2,2-trifluoro-isopropoxy)-3-chlorophenyl]carbonylamino}(2S)-3-[4-(2-acetyl-1-methylimidazol-4-yl)phenyl]propyl)-2-azetidinylacetamide;
N-(2-{[4-((1R)-2,2,2-trifluoro-isopropoxy)-3-chlorophenyl]carbonylamino}(2S)-3-{4-[2-(hydroxyethyl)-1-methylimidazol-4-yl]phenyl}propyl)-2-azetidinylacetamide;
N-(2-{[4-((1R)-2,2,2-trifluoro-isopropoxy)-3-chlorophenyl]carbonylamino}(2S)-3-{4-[1-ethyl-2-(1-hydroxy-isopropyl)imidazol-4-yl]phenyl}propyl)-2-azetidinylacetamide; and
N-((2S)-2-{[3-chloro-4-(methylethoxy)phenyl]carbonylamino}-3-{4-[1-ethyl-2-(1-hydroxy-isopropyl)imidazol-4-yl]phenyl}propyl)-2-azetidinylacetamide and pharmaceutically acceptable salts thereof.
6. A composition comprising a pharmaceutical excipient and at least one compound of claim 5 , or a pharmaceutically acceptable salt thereof.