Fused heterocyclyc inhibitor compounds
The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) and/or Cyclin-dependent kinase (CDK) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.
1. A compound selected from those of Formula (I) and pharmaceutically acceptable salts thereof:
wherein
R 1 is selected from the group consisting of H, halo, nitro, cyano, hydroxy, hydroxy(C 1-10 alkyl), amino(C 1-10 alkyl), haloalkyl, haloalkoxy, amino, azido, carboxyl, carbamoyl, mercapto, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, hydroxy(C 1-10 alkoxy)(C 1-10 alkoxy), (C 1-10 alkoxy)(C 1-10 alkoxy), (C 1-10 alkoxy)(C 1-10 alkyl), C 1-10 alkanoyl, C 1-10 alkanoyloxy, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 -amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 -carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, C 1-10 alkoxycarbonyl, NH 2 —S(O) 2 NH—, NH 2 —CO—NH—, N—(C 1-10 alkyl)sulphamoyl, N,N—(C 1-10 alkyl) 2 sulphamoyl, aryl, arylalkyl, aryloxy, arylthio, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyl(C═O)—, heterocyclyloxy and heterocyclylthio, wherein R 1 is optionally substituted by one or more A;
Q 1 and Q 2 together form a cyclic moiety to make a fused ring together with the imidazole moiety, wherein the cyclic moiety is substituted by one or more substituents selected from R 1 groups, each of which is optionally substituted by one or more A;
U 1 , U 2 , U 3 and U 4 are independently selected from —N—, —CH—, and —CR 6 —, with the proviso that at least one of U 1 , U 2 , U 3 and U 4 is —N—;
m is 0, 1, 2, or 3;
R 6 is halo, hydroxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, amino, carboxyl, carbamoyl, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkanoyl, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, NH 2 —S(O) 2 NH—, N—(C 1-10 alkyl)sulphamoyl or N,N—(C 1-10 alkyl) 2 sulphamoyl; wherein R 6 is optionally substituted by one or more B;
X is phenyl, 5-membered heteroaryl, or 6-membered heteroaryl, wherein the heteroaryl contains one or more heteroatoms selected from N, S and O;
R 7 represents one or more optional non-hydrogen substituents on ring X, wherein when present, each R 7 is independently selected from hydroxy, halo, nitro, cyano, trifluoromethyl, trifluoromethoxy, amino, carboxyl, carbamoyl, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkanoyl, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, NH 2 —S(O) 2 NH—, N—(C 1-10 alkyl)sulphamoyl, N,N—(C 1-10 alkyl) 2 sulphamoyl, cycloalkyl, heterocyclyl and aryl;
n is 0, 1, 2, 3 or 4;
R 8 is hydroxy, aryl or heteroaryl, wherein aryl or heteroaryl is substituted with —NH 2 or —OH and aryl or heteroaryl is optionally further substituted with one or more groups selected from amino, halo, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, haloaryl, haloheterocyclyl, wherein alkyl, alkenyl, or alkynyl is optionally further substituted with one or more groups selected from halo, hydroxy, alkyl, haloalkyl and cycloalkyl;
R 9 is H, alkyl, haloalkyl, aminoalkyl, cycloalkyl, heterocyclyl, or aryl, wherein R 9 is optionally substituted by one or more D; and
A, B and D are independently selected from halo, nitro, cyano, hydroxy, oxo, hydroxyalkyl, haloalkyl, haloalkoxy, amino, azido, carboxyl, carbamoyl, mercapto, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkanoyl, C 1-10 alkanoyloxy, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 -amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 -carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, C 1-10 alkoxycarbonyl, N—(C 1-10 alkyl)sulphamoyl, N,N—(C 1-10 alkyl) 2 sulphamoyl, H 2 NS(O) 2 NH—, N—(C 1-10 alkyl)NHS(O) 2 NH—, N,N—(C 1-10 alkyl) 2 NS(O) 2 NH—, aryl, aryloxy, arylthio, cycloalkyl, cycloalkyloxy, heterocyclyl, heterocyclyl(C═O)—, heterocyclyloxy and heterocyclylthio.
2. The compound of claim 1 , wherein R 8 is hydroxy, phenyl or 5-membered or 6-membered heteroaryl, wherein phenyl or heteroaryl is substituted with —NH 2 or —OH at a ring position adjacent to attachment of the —CONH-moiety, and phenyl or heteroaryl is optionally further substituted with one or more substituent selected from amino, halo, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, haloaryl, haloheterocyclyl, wherein alkyl, alkenyl, or alkynyl is optionally further substituted with one or more groups selected from halo, hydroxy, alkyl, haloalkyl and cycloalkyl.
3. The compound according to claim 1 , wherein Q 1 and Q 2 together with the imidazole ring to which they are attached form a cyclic moiety to make a fused aromatic ring system selected from the group consisting of:
wherein the wavy lines show the point of attachment to the 6-membered nitrogen containing heteroaryl and wherein R 2 , R 3 , R 4 , and R 5 are independently selected from groups R 1 optionally substituted with one or more A.
4. The compound according to claim 1 , wherein U 1 , U 2 , U 3 and U 4 are selected to form any of the following heteroaryl moieties
5. The compound of claim 1 selected from those of Formulae (I a ), (I b ) and (I c ) and pharmaceutically acceptable salts thereof:
6. The compound of claim 5 selected from those of Formulae (I a -a), (I a -b), (I a -c), (I a -d), (I a -e), (I a -f), (I a -g), and (I a -h), and pharmaceutically acceptable salts thereof:
wherein
R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of H, halo, nitro, cyano, hydroxy, hydroxyalkyl, haloalkyl, haloalkoxy, amino, azido, carboxyl, carbamoyl, mercapto, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkanoyl, C 1-10 alkanoyloxy, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 -amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 -carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, C 1-10 alkoxycarbonyl, NH 2 —S(O) 2 NH—, N—(C 1-10 alkyl)sulphamoyl, N,N—(C 1-10 alkyl) 2 sulphamoyl, aryl, aryloxy, arylthio, cycloalkyl, cycloalkyloxy, heterocyclyl, heterocyclyl(C═O)—, heterocyclyloxy and heterocyclylthio; wherein each of R 1 , R 2 , R 3 , R 4 and R 5 is optionally substituted by one or more A; and
V 1 , V 2 , V 3 , V 4 , V 5 , V 6 , and V 7 are ring atoms independently selected from N, O, S, and C.
7. The compound of claim 6 selected from those of Formula (I a -a), wherein at least two of R 1 , R 2 , R 3 , R 4 and R 5 are H, and each non-hydrogen R 1 , R 2 , R 3 , R 4 and R 5 is independently selected from the group consisting of chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, acetyl, carboxyl, methylcarboxyl, cyano, methoxymethyl, ethoxyethyl, propoxyethyl, methoxyethoxy, trifluoromethyl, hydroxyethoxy, dimethylamino, diethylamino, dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl, dimethylaminoethoxy, dimethylaminocarbonyl, dimethylaminoethylamide, trifluoromethoxymethyl, trifluoroethoxymethyl, isopropylcarbonyl, 1-hydroxyethyl, 3-oxetanoxy, trifluoroethylaminomethyl, N-methyl-N-methoxyethyl-aminomethyl, cyclopropanylmethyl, cyclopropyl, cyclobutoxy, 1-cyclopropanylethoxy, cyclopropanylmethylaminomethyl, 4-methylpiperazin-1-carbonyl, isoindolin-2-yl, N-methoxyethylcarbamoyl, N-(morpholin-4-yl)-ethylcarbamoyl, dimethylaminoethylamino, N,N-dimethylaminoethylcarbamoyl, benzyl, phenylethyl, trifluoromethylphenylethyl, phenoxymethyl, fluorophenoxymethyl, phenylethylaminomethyl, benzylaminomethyl, triazinylmethyl, piperidinylmethyl, piperidinyloxy, trifluoromethylpiperidinylmethyl, pyridinyloxymethyl, pyridinylmethoxy, tetrahydropyrazinyloxy, methylpiperazinylmethyl, methanesulfonyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, pyrrolidin-1-ylethoxy, pyrrolidin-2-ylethoxy, pyrrolidin-3-ylethoxy, thiazol-4-yl, 2-methyl-thiazol-4-yl, imidazol-1-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, imidazolidin-1-ylmethyl, imidazolidin-2-ylmethyl, imidazolidin-4-ylmethyl, imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolin-1-yl, pyrazolin-3-yl, pyrazolin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-1-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-2-ylmethyl, morpholin-3-ylmethyl, morpholin-4-ylmethyl, morpholin-4-ylsulfonyl, morpholin-2-ylethoxy, morpholin-3-ylethoxy and morpholin-4-ylethoxy;
n is 0, 1, or 2 and m is 0 or 1;
R 6 , if present, is halo, hydroxy, alkyl or haloalkyl;
R 7 , if present, is fluoro, chloro, bromo, or methyl; and
R 8 is hydroxy, 2-hydroxyphenyl, 2-aminophenyl, 2-amino-6-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-5-trifluoromethylphenyl, 4-aminobiphenyl-3-yl, 4′-fluoro-4-aminobiphenyl-3-yl, 2-amino-5-(thiophen-2-yl)phenyl, 5′-chloro-2-amino-5-(thiophen-2-yl)phenyl, 5′-methyl-2-amino-5-(thiophen-2-yl)phenyl, 2-amino-5-(thiophen-3-yl)phenyl, 2-aminopyridin-3-yl, 4-amino-1-phenyl-1H-pyrazol-3-yl, 2-amino-5-(3-hydroxy-3-methylbut-1-ynyl)phenyl, 2-amino-5-(4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl)phenyl, 2-amino-5-(3-cyclopropylprop-1-ynyl)phenyl or 2-amino-5-(3-(1-hydroxycyclopropyl)prop-1-ynyl)phenyl.
8. The compound of claim 7 which is selected from the group consisting of:
N-hydroxy-4-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-3-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(imidazo[1,2-a]pyridin-3-yl)-5-methylpyrimidin-2-ylamino)benzamide;
N-hydroxy-3-(4-(imidazo[1,2-a]pyridin-3-yl)-5-methylpyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-3-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-a]pyridin-3-yl)-5-methylpyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-3-(4-(imidazo[1,2-a]pyridin-3-yl)-5-methylpyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-3-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(5-methyl-4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-3-(5-methyl-4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-3-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(5-methyl-4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-3-(5-methyl-4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(6-chloro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(6-chloro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(7-((dimethylamino)methyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-((dimethylamino)methyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-(pyrrolidin-1-ylmethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-(pyrrolidin-1-ylmethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-(morpholinomethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-(morpholinomethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-N-(2-methoxyethyl)-2-methylimidazo[1,2-a]pyridine-7-carboxamide;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-N-(2-methoxyethyl)-2-methylimidazo[1,2-a]pyridine-7-carboxamide;
4-(4-(7-cyano-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-cyano-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methyl-N-(2-morpholinoethyl)imidazo[1,2-a]pyridine-7-carboxamide;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methyl-N-(2-morpholinoethyl)imidazo[1,2-a]pyridine-7-carboxamide;
methyl 3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylate;
methyl 3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylate;
N-hydroxy-4-(4-(2-methyl-7-(4-methylpiperazine-1-carbonyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(4-methylpiperazine-1-carbonyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylic acid;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylic acid;
N-hydroxy-4-(4-(2-methyl-7-(2-morpholinoethoxy)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(2-morpholinoethoxy)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(7-(2-(dimethylamino)ethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-(2-(dimethylamino)ethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-(2-methoxyethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-(2-methoxyethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(7-(2-(dimethylamino)ethylamino)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-(2-(dimethylamino)ethylamino)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-N-(2-methoxyethyl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-N-(2-methoxyethyl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide;
N-hydroxy-4-(4-(2-methyl-6-(4-methylpiperazine-1-carbonyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-6-(4-methylpiperazine-1-carbonyl)imidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)benzamide;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methyl-N-(2-morpholinoethyl)imidazo[1,2-a]pyridine-6-carboxamide;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methyl-N-(2-morpholinoethyl)imidazo[1,2-a]pyridine-6-carboxamide;
N-hydroxy-4-(4-(6-(2-methoxyethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(6-(2-methoxyethoxy)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(6-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(6-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(8-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(8-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(7-((dimethylamino)methyl)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-((dimethylamino)methyl)-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
4-(4-(7-cyano-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(4-(7-cyano-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
methyl 3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylate;
methyl 3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylate;
3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylic acid;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-7-carboxylic acid;
3-fluoro-N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-3-fluoro-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
2-fluoro-N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-2-fluoro-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-(dimethylamino)ethyl)-3-(2-(4-(hydroxycarbamoyl)phenylamino)pyrimidin-4-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide;
3-(2-(4-(2-aminophenylcarbamoyl)phenylamino)pyrimidin-4-yl)-N-(2-(dimethylamino)ethyl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide;
4-(5-fluoro-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-N-hydroxybenzamide;
N-(2-Amino-phenyl)-4-[4-(2-methyl-7-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamino]-benzamide;
N-(2-aminophenyl)-4-(5-fluoro-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)benzamide; and
pharmaceutically acceptable salts thereof.
9. The compound of claim 6 selected from those of Formulae (I a -b0), (I a -b1), and (I a -b2) and pharmaceutically acceptable salts thereof:
wherein R 6′ is H or R 6 .
10. The compound of claim 9 which is selected from the group consisting of:
N-hydroxy-5-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(7-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(7-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-3-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-3-carboxamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiophene-2-carboxamide; and
pharmaceutically acceptable salts thereof.
11. The compound of claim 6 selected from those of Formula (I a -c), wherein at least two of R 1 , R 2 , R 3 and R 4 are H, and each of non-hydrogen R 1 , R 2 , R 3 and R 4 is independently selected from the group consisting of chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, acetyl, carboxyl, methylcarboxyl, cyano, methoxymethyl, ethoxyethyl, propoxyethyl, methoxyethoxy, trifluoromethyl, hydroxyethoxy, dimethylamino, diethylamino, dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl, dimethylaminoethoxy, dimethylaminocarbonyl, dimethylaminoethylamide, trifluoromethoxymethyl, trifluoroethoxymethyl, isopropylcarbonyl, 1-hydroxyethyl, 3-oxetanoxy, trifluoroethylaminomethyl, N-methyl-N-methoxyethyl-aminoethyl, cyclopropanylmethyl, cyclopropyl, cyclobutoxy, 1-cyclopropanylethoxy, cyclopropanylmethylaminomethyl, 4-methylpiperazin-1-carbonyl, isoindolin-2-yl, N-methoxyethylcarbamoyl, N-(morpholin-4-yl)-ethylcarbamoyl, dimethylaminoethylamino, N,N-dimethylaminoethylcarbamoyl, benzyl, phenylethyl, trifluoromethylphenylethyl, phenoxymethyl, fluorophenoxymethyl, phenylethylaminomethyl, benzylaminomethyl, triazinylmethyl, piperidinylmethyl, piperidinyloxy, trifluoromethylpiperidinylmethyl, pyridinyloxymethyl, pyridinylmethoxy, tetrahydropyrazinyloxy, methylpiperazinylmethyl, methanesulfonyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, pyrrolidin-1-ylethoxy, pyrrolidin-2-ylethoxy, pyrrolidin-3-ylethoxy, thiazol-4-yl, 2-methyl-thiazol-4-yl, imidazol-1-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, imidazolidin-1-ylmethyl, imidazolidin-2-ylmethyl, imidazolidin-4-ylmethyl, imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolin-1-yl, pyrazolin-3-yl, pyrazolin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-1-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-2-ylmethyl, morpholin-3-ylmethyl, morpholin-4-ylmethyl, morpholin-4-ylsulfonyl, morpholin-2-ylethoxy, morpholin-3-ylethoxy and morpholin-4-ylethoxy;
n is 0, 1, or 2 and m is 0 or 1;
R 6 , if present, is halo, hydroxy, alkyl or haloalkyl;
R 7 , if present, is fluoro, chloro, bromo, or methyl; and
R 8 is hydroxy, 2-hydroxyphenyl, 2-aminophenyl, 2-amino-6-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-5-trifluoromethylphenyl, 4-aminobiphenyl-3-yl, 4′-fluoro-4-aminobiphenyl-3-yl, 2-amino-5-(thiophen-2-yl)phenyl, 5′-chloro-2-amino-5-(thiophen-2-yl)phenyl, 5′-methyl-2-amino-5-(thiophen-2-yl)phenyl, 2-amino-5-(thiophen-3-yl)phenyl, 2-aminopyridin-3-yl, 4-amino-1-phenyl-1H-pyrazol-3-yl, 2-amino-5-(3-hydroxy-3-methylbut-1-ynyl)phenyl, 2-amino-5-(4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl)phenyl, 2-amino-5-(3-cyclopropylprop-1-ynyl)phenyl or 2-amino-5-(3-(1-hydroxycyclopropyl)prop-1-ynyl)phenyl.
12. The compound of claim 11 which is selected from the group consisting of:
N-hydroxy-4-(4-(imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methylimidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-methylimidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-methylimidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-b]pyridazin-3-yl)pyrimidin-2-ylamino)benzamide; and
pharmaceutically acceptable salts thereof.
13. The compound of claim 6 selected from those of Formula (I a -d), wherein at least two of R 1 , R 2 , R 3 and R 5 are H, and each of non-hydrogen R 1 , R 2 , R 3 and R 5 is independently selected from the group consisting of chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, acetyl, carboxyl, methylcarboxyl, cyano, methoxymethyl, ethoxyethyl, propoxyethyl, methoxyethoxy, trifluoromethyl, hydroxyethoxy, dimethylamino, diethylamino, dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl, dimethylaminoethoxy, dimethylaminocarbonyl, dimethylaminoethylamide, trifluoromethoxymethyl, trifluoroethoxymethyl, isopropylcarbonyl, 1-hydroxyethyl, 3-oxetanoxy, trifluoroethylaminomethyl, N-methyl-N-methoxyethyl-aminoethyl, cyclopropanylmethyl, cyclopropyl, cyclobutoxy, 1-cyclopropanylethoxy, cyclopropanylmethylaminomethyl, 4-methylpiperazin-1-carbonyl, isoindolin-2-yl, N-methoxyethylcarbamoyl, N-(morpholin-4-yl)-ethylcarbamoyl, dimethylaminoethylamino, N,N-dimethylaminoethylcarbamoyl, benzyl, phenylethyl, trifluoromethylphenylethyl, phenoxymethyl, fluorophenoxymethyl, phenylethylaminomethyl, benzylaminomethyl, triazinylmethyl, piperidinylmethyl, piperidinyloxy, trifluoromethylpiperidinylmethyl, pyridinyloxymethyl, pyridinylmethoxy, tetrahydropyrazinyloxy, methylpiperazinylmethyl, methanesulfonyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, pyrrolidin-1-ylethoxy, pyrrolidin-2-ylethoxy, pyrrolidin-3-ylethoxy, thiazol-4-yl, 2-methyl-thiazol-4-yl, imidazol-1-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, imidazolidin-1-ylmethyl, imidazolidin-2-ylmethyl, imidazolidin-4-ylmethyl, imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolin-1-yl, pyrazolin-3-yl, pyrazolin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-1-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-2-ylmethyl, morpholin-3-ylmethyl, morpholin-4-ylmethyl, morpholin-4-ylsulfonyl, morpholin-2-ylethoxy, morpholin-3-ylethoxy and morpholin-4-ylethoxy;
n is 0, 1, or 2 and m is 0 or 1;
R 6 , if present, is halo, hydroxy, alkyl or haloalkyl;
R 7 , if present, is fluoro, chloro, bromo, or methyl; and
R 8 is hydroxy, 2-hydroxyphenyl, 2-aminophenyl, 2-amino-6-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-5-trifluoromethylphenyl, 4-aminobiphenyl-3-yl, 4′-fluoro-4-aminobiphenyl-3-yl, 2-amino-5-(thiophen-2-yl)phenyl, 5′-chloro-2-amino-5-(thiophen-2-yl)phenyl, 5′-methyl-2-amino-5-(thiophen-2-yl)phenyl, 2-amino-5-(thiophen-3-yl)phenyl, 2-aminopyridin-3-yl, 4-amino-1-phenyl-1H-pyrazol-3-yl, 2-amino-5-(3-hydroxy-3-methylbut-1-ynyl)phenyl, 2-amino-5-(4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl)phenyl, 2-amino-5-(3-cyclopropylprop-1-ynyl)phenyl or 2-amino-5-(3-(1-hydroxycyclopropyl)prop-1-ynyl)phenyl.
14. The compound of claim 13 which is selected from the group consisting of:
N-hydroxy-4-(4-(imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methylimidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-methylimidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-methylimidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-c]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide; and
pharmaceutically acceptable salts thereof.
15. The compound of claim 6 selected from those of Formula (I a -e), wherein
at least two of R 1 , R 2 , R 4 and R 5 are H, and each of non-hydrogen R 1 , R 2 , R 4 and R 5 is independently selected from the group consisting of chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, acetyl, carboxyl, methylcarboxyl, cyano, methoxymethyl, ethoxyethyl, propoxyethyl, methoxyethoxy, trifluoromethyl, hydroxyethoxy, dimethylamino, diethylamino, dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl, dimethylaminoethoxy, dimethylaminocarbonyl, dimethylaminoethylamide, trifluoromethoxymethyl, trifluoroethoxymethyl, isopropylcarbonyl, 1-hydroxyethyl, 3-oxetanoxy, trifluoroethylaminomethyl, N-methyl-N-methoxyethyl-aminoethyl, cyclopropanylmethyl, cyclopropyl, cyclobutoxy, 1-cyclopropanylethoxy, cyclopropanylmethylaminomethyl, 4-methylpiperazin-1-carbonyl, isoindolin-2-yl, N-methoxyethylcarbamoyl, N-(morpholin-4-yl)-ethylcarbamoyl, dimethylaminoethylamino, N,N-dimethylaminoethylcarbamoyl, benzyl, phenylethyl, trifluoromethylphenylethyl, phenoxymethyl, fluorophenoxymethyl, phenylethylaminomethyl, benzylaminomethyl, triazinylmethyl, piperidinylmethyl, piperidinyloxy, trifluoromethylpiperidinylmethyl, pyridinyloxymethyl, pyridinylmethoxy, tetrahydropyrazinyloxy, methylpiperazinylmethyl, methanesulfonyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, pyrrolidin-1-ylethoxy, pyrrolidin-2-ylethoxy, pyrrolidin-3-ylethoxy, thiazol-4-yl, 2-methyl-thiazol-4-yl, imidazol-1-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, imidazolidin-1-ylmethyl, imidazolidin-2-ylmethyl, imidazolidin-4-ylmethyl, imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolin-1-yl, pyrazolin-3-yl, pyrazolin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-1-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-2-ylmethyl, morpholin-3-ylmethyl, morpholin-4-ylmethyl, morpholin-4-ylsulfonyl, morpholin-2-ylethoxy, morpholin-3-ylethoxy and morpholin-4-ylethoxy;
n is 0, 1, or 2 and m is 0 or 1;
R 6 , if present, is halo, hydroxy, alkyl or haloalkyl;
R 7 , if present, is fluoro, chloro, bromo, or methyl; and
R 8 is hydroxy, 2-hydroxyphenyl, 2-aminophenyl, 2-amino-6-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-5-trifluoromethylphenyl, 4-aminobiphenyl-3-yl, 4′-fluoro-4-aminobiphenyl-3-yl, 2-amino-5-(thiophen-2-yl)phenyl, 5′-chloro-2-amino-5-(thiophen-2-yl)phenyl, 5′-methyl-2-amino-5-(thiophen-2-yl)phenyl, 2-amino-5-(thiophen-3-yl)phenyl, 2-aminopyridin-3-yl, 4-amino-1-phenyl-1H-pyrazol-3-yl, 2-amino-5-(3-hydroxy-3-methylbut-1-ynyl)phenyl, 2-amino-5-(4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl)phenyl, 2-amino-5-(3-cyclopropylprop-1-ynyl)phenyl or 2-amino-5-(3-(1-hydroxycyclopropyl)prop-1-ynyl)phenyl.
16. The compound of claim 15 which is selected from the group consisting of:
N-hydroxy-4-(4-(imidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methylimidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)pyrimidin-2-ylamino)benzamide; and
pharmaceutically acceptable salts thereof.
17. The compound of claim 6 selected from those of Formula (I a -f), wherein
at least two of R 1 , R 3 , R 4 and R 5 are H, and each of non-hydrogen R 1 , R 3 , R 4 and R 5 is independently selected from the group consisting of chloro, fluoro, bromo, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, acetyl, carboxyl, methylcarboxyl, cyano, methoxymethyl, ethoxyethyl, propoxyethyl, methoxyethoxy, trifluoromethyl, hydroxyethoxy, dimethylamino, diethylamino, dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl, dimethylaminoethoxy, dimethylaminocarbonyl, dimethylaminoethylamide, trifluoromethoxymethyl, trifluoroethoxymethyl, isopropylcarbonyl, 1-hydroxyethyl, 3-oxetanoxy, trifluoroethylaminomethyl, N-methyl-N-methoxyethyl-aminoethyl, cyclopropanylmethyl, cyclopropyl, cyclobutoxy, 1-cyclopropanylethoxy, cyclopropanylmethylaminomethyl, 4-methylpiperazin-1-carbonyl, isoindolin-2-yl, N-methoxyethylcarbamoyl, N-(morpholin-4-yl)-ethylcarbamoyl, dimethylaminoethylamino, N,N-dimethylaminoethylcarbamoyl, benzyl, phenylethyl, trifluoromethylphenylethyl, phenoxymethyl, fluorophenoxymethyl, phenylethylaminomethyl, benzylaminomethyl, triazinylmethyl, piperidinylmethyl, piperidinyloxy, trifluoromethylpiperidinylmethyl, pyridinyloxymethyl, pyridinylmethoxy, tetrahydropyrazinyloxy, methylpiperazinylmethyl, methanesulfonyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, pyrrolidin-1-ylethoxy, pyrrolidin-2-ylethoxy, pyrrolidin-3-ylethoxy, thiazol-4-yl, 2-methyl-thiazol-4-yl, imidazol-1-ylmethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, imidazolidin-1-ylmethyl, imidazolidin-2-ylmethyl, imidazolidin-4-ylmethyl, imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolin-1-yl, pyrazolin-3-yl, pyrazolin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-1-ylmethyl, piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-2-ylmethyl, morpholin-3-ylmethyl, morpholin-4-ylmethyl, morpholin-4-ylsulfonyl, morpholin-2-ylethoxy, morpholin-3-ylethoxy and morpholin-4-ylethoxy;
n is 0, 1, or 2 and m is 0 or 1;
R 6 , if present, is halo, hydroxy, alkyl or haloalkyl;
R 7 , if present, is fluoro, chloro, bromo, or methyl; and
R 8 is hydroxy, 2-hydroxyphenyl, 2-aminophenyl, 2-amino-6-fluorophenyl, 2-amino-5-fluorophenyl, 2-amino-5-trifluoromethylphenyl, 4-aminobiphenyl-3-yl, 4′-fluoro-4-aminobiphenyl-3-yl, 2-amino-5-(thiophen-2-yl)phenyl, 5′-chloro-2-amino-5-(thiophen-2-yl)phenyl, 5′-methyl-2-amino-5-(thiophen-2-yl)phenyl, 2-amino-5-(thiophen-3-yl)phenyl, 2-aminopyridin-3-yl, 4-amino-1-phenyl-1H-pyrazol-3-yl, 2-amino-5-(3-hydroxy-3-methylbut-1-ynyl)phenyl, 2-amino-5-(4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl)phenyl, 2-amino-5-(3-cyclopropylprop-1-ynyl)phenyl or 2-amino-5-(3-(1-hydroxycyclopropyl)prop-1-ynyl)phenyl.
18. The compound of claim 17 which is selected from the group consisting of:
N-hydroxy-4-(4-(imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-Amino-phenyl)-4-[4-(2-methyl-imidazo[1,2-a]pyrimidin-3-yl)-pyrimidin-2-ylamino]-benzamide;
N-hydroxy-4-(4-(7-methoxy-2-methylimidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-methylimidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-hydroxy-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(7-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-ylamino)benzamide; and
pharmaceutically acceptable salts thereof.
19. The compound of claim 6 selected from those of Formulae (I a -g0), (I a -g1), (I a -g2), and (I a -g3), and pharmaceutically acceptable salts thereof:
wherein R 6′ is H or R 6 , and R 7′ is H or R 7 .
20. The compound of claim 19 which is selected from the group consisting of:
N-hydroxy-6-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)nicotinamide;
N-(2-aminophenyl)-6-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)nicotinamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)pyrazine-2-carboxamide;
N-(2-aminophenyl)-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)pyrazine-2-carboxamide;
N-hydroxy-6-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)nicotinamide;
N-(2-aminophenyl)-6-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)nicotinamide;
N-hydroxy-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)pyrimidine-5-carboxamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)pyrazine-2-carboxamide;
N-hydroxy-6-(4-(7-methoxy-2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)nicotinamide; and
pharmaceutically acceptable salts thereof.
21. The compound of claim 6 selected from those of Formulae (I a -h0), (I a -h1), and (I a -h2), and pharmaceutically acceptable salts thereof:
wherein R 6′ is H or R 6 .
22. The compound of claim 21 which is selected from the group consisting of:
N-(2-aminophenyl)-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiazole-4-carboxamide;
N-(2-aminophenyl)-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiazole-5-carboxamide;
N-hydroxy-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiazole-4-carboxamide;
N-hydroxy-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)thiazole-5-carboxamide;
N-hydroxy-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)oxazole-5-carboxamide;
N-hydroxy-2-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)thiazole-5-carboxamide;
N-hydroxy-5-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)-1,3,4-thiadiazole-2-carboxamide; and
pharmaceutically acceptable salts thereof.
23. The compound of claim 5 selected from those of Formula (I b -a) and pharmaceutically acceptable salts thereof:
wherein
R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of H, halo, nitro, cyano, hydroxy, hydroxyalkyl, haloalkyl, haloalkoxy, amino, azido, carboxyl, carbamoyl, mercapto, sulphamoyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, C 1-10 alkanoyl, C 1-10 alkanoyloxy, N—(C 1-10 alkyl)amino, N,N—(C 1-10 alkyl) 2 -amino, C 1-10 alkanoylamino, N—(C 1-10 alkyl)carbamoyl, N,N—(C 1-10 alkyl) 2 -carbamoyl, C 1-10 alkyl-S(O) a wherein a is 0, 1 or 2, C 1-10 alkoxycarbonyl, NH 2 —S(O) 2 NH—, N—(C 1-10 alkyl)sulphamoyl, N,N—(C 1-10 alkyl) 2 sulphamoyl, aryl, aryloxy, arylthio, cycloalkyl, cycloalkyloxy, heterocyclyl, heterocyclyl(C═O)—, heterocyclyloxy and heterocyclylthio; wherein each of R 1 , R 2 , R 3 , R 4 and R 5 is optionally substituted by one or more A.
24. The compound of claim 23 selected from those of Formulae (I b -a1), (I b -a2) (I b -a3) and (I b -a4) and pharmaceutically acceptable salts thereof:
wherein R 6′ is H or R 6 ; and R 7′ is H or R 7 .
25. The compound of claim 24 which is selected from the group consisting of:
N-hydroxy-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyridin-2-ylamino)benzamide;
N-hydroxy-4-(5-(imidazo[1,2-a]pyridin-3-yl)pyridazin-3-ylamino)benzamide;
N-(2-aminophenyl)-4-(5-(imidazo[1,2-a]pyridin-3-yl)pyridazin-3-ylamino)benzamide;
N-hydroxy-4-(4-(imidazo[1,2-a]pyridin-3-yl)-1,3,5-triazin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(4-(imidazo[1,2-a]pyridin-3-yl)-1,3,5-triazin-2-ylamino)benzamide;
N-(2-aminophenyl)-4-(6-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-4-ylamino)benzamide;
and pharmaceutically acceptable salts thereof.
26. The compound of claim 5 selected from those of Formulae (I c -a) and (I c -b) and pharmaceutically acceptable salts thereof:
wherein R 9 is alkyl, haloalkyl or aminoalkyl; and m is 0 or 1.
27. The compound of claim 26 which is selected from the group consisting of:
N-hydroxy-4-((4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)(methyl)amino)benzamide;
N-(2-aminophenyl)-4-((4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)(methyl)amino)benzamide;
4-(ethyl(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)amino)-N-hydroxybenzamide;
N-(2-aminophenyl)-4-(ethyl(4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)amino)benzamide;
N-hydroxy-4-((4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)(2,2,2-trifluoroethyl)amino)benzamide;
N-(2-aminophenyl)-4-((4-(imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl)(2,2,2-trifluoroethyl)amino)benzamide; and
pharmaceutically acceptable salts thereof.
28. A pharmaceutical composition comprising an effective amount of one or more compounds according to claim 1 and a pharmaceutically-acceptable carrier.
29. The pharmaceutical composition according to claim 28 , further comprising one or more anti-cancer agents selected from the group consisting of cyclophosphamide, dacarbazine, cisplatin, methotrexate, mercaptopurine, thioguanine, fluorouracil, cytarabine, vinblastine, paclitaxel, doxorubicin, bleomycin, mitomycin, prednisone, tamoxifen, flutamide, asparaginase, rituximab, trastuzumab, imatinib, retinoic acid, colony-stimulating factor, amifostine, lenalidomide, HDAC inhibitor, CDK inhibitor, camptothecin and topotecan.