Compounds and Compositions as Protein Kinase Inhibitors
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Abstract
The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, ΣΓK, Ttε2, Λχκ, ΘNK2α2, MKK4, c-RAF, MKK6, SAPK2α and SAPK2β kinases.
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Citations
9 Claims
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1. A compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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2. The compound of claim 1 of Formula Ia:
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3. The compound of claim 2 in which R5 is selected from hydrogen, morpholino-ethyl, cyclopropyl, methyl, 3-(2-oxo-pyrrolidin-1-yl)-propyl, benzo[1,3]dioxol-5-yl, 3-(4-methyl-piperazin-1-yl)-propyl, hydroxymethyl-phenyl, (1-hydroxyethyl)-phenyl, morpholino, pyridinyl, methyl-carbonyl, methyl-sulfonyl, methyl-pyridinyl, amino-cyclohexyl, piperidinyl, methyl-piperazinyl-ethyl, dimethyl-pyrazolyl, methyl-pyrazolyl, dimethyl-pyridinyl, methyl-pyridinyl, ethyl-piperazinyl-pyridinyl, amino-carbonyl-pyridinyl, cyano-pyridinyl, dimethyl-amino-ethyl, methoxy-ethyl, methyl-pyrrolidinyl-ethyl, ethyl-pyrazolyl, dimethyl-amino-propyl, isopropyl, furanyl-methyl, methyl-piperazinyl-propyl, benzo[1,3]dioxol-5-ylmethyl, 2-methyl-6-morpholin-4-yl-pyridin-3-yl, methyl-pyrimidinyl, methoxy-pyridinyl, fluoro-phenyl, dimethyl-amino-ethyl-aminocarbonyl, pyridinyl-methyl, thiazolyl-methyl, methyl-pyrazinyl-methyl, imidazolyl-propyl, amino-carbonyl-phenyl, ;
- or R5 and R6 together with the nitrogen atom to which they are both attached form a group selected from morpholino, piperidinyl and piperazinyl optionally substituted with a group selected from ethyl, pyridinyl and morpholino.
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4. The compound of claim 3 in which R16 is selected from —
- NHC(O)R13, —
NHC(O)NHR13, —
C(O)NHR13, —
NHS(O)2R13 and —
S(O)2NHR13;
wherein R13 is selected from phenyl, pyridazinyl, pyridinyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, quinoxalinyl, thienyl and thiazolyl;
wherein R13 is optionally substituted with 1 to 3 radicals independently selected from methyl, t-butyl, halo, trifluoromethyl, diethyl-amino, dimethyl-amino, benzyl, piperidinyl-amino, pyrrolidinyl-methoxy, ethyl-piperazinyl-methyl, morpholino, methyl-piperazinyl, methyl-piperazinyl-methyl, ethyl-piperazinyl, methyl-imidazolyl, morpholino-methyl, pyrrolidinyl-piperidinyl, piperazinyl-methyl, hydroxy-piperidinyl, 1-methyl-piperidin-4-yloxy, piperidinyl-oxy, methyl-pyrazinyl, pyrazinyl and hydroxyethyl-piperazinyl.
- NHC(O)R13, —
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5. The compound of claim 1 selected from N-[4-methyl-3-(1-{6-[4-(2-morpholin-4-yl-ethyl)-phenylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3 -trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-ethyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-(4-methyl-3-{-1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-(3-{1-[6-(benzo[1,3]dioxol-5-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, {6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-cyclopropyl-amine, (3-{6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-ylamino}-phenyl)-methanol, 1-(3-{6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-ylamino}-phenyl)-ethanol, {6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-[4-(2-morpholin-4-yl-ethyl)-phenyl]-amine, {6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-(4-morpholin-4-yl-phenyl)-amine, N-(3-{6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-ylamino}-phenyl)-acetamide, 1-(3-{6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-ylamino }-propyl)-pyrrolidin-2-one, benzo[1,3]dioxol-5-yl-{6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-amine, {6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-pyridin-3-yl-amine, N-(4-methyl-3-{1-[6-(pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, {6-[2-(2-chloro-phenylamino)-imidazol-1-yl]-pyrimidin-4-yl}-(6-methyl-pyridin-3 -yl)-amine, N-(4-methyl-3-{1-[6-(6-methyl-pyridin-3 -ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-morpholin-4-yl-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-ethyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-morpholin-4-yl-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, 3-(4-methyl-imidazol-1-yl)-N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-5-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-4-morpholin-4-yl-3-trifluoromethyl-benzamide, 3-(4-ethyl-piperazin-1-yl)-N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-5-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, 3-(4-ethyl-piperazin-1-ylmethyl)-N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-morpholin-4-ylmethyl-3-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(6-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-4-morpholin-4-ylmethyl-3-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-morpholin-4-yl-3-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-ethyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-morpholin-4-ylmethyl-5-trifluoromethyl-benzamide, 3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-5-methoxy-N-[4-(2-methyl-imidazol-1-yl)-3-trifluoromethyl-phenyl]-benzamide, N-{3-[1-(6-acetylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, N-{3-[1-(6-methanesulfonylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, N-{3-[1-(2-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, 3-[1-(2-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-N-[4-(2-methyl-imidazol-1-yl)-3-trifluoromethyl-phenyl]-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-piperazin-1-ylmethyl-5-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-piperazin-1-ylmethyl-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-5-methoxy-phenyl}-4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-5-methoxy-phenyl}-3-(4-ethyl-piperazin-1-ylmethyl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(piperidin-4-yloxy)-5-trifluoromethyl-benzamide, N-{3-[1-(6-amino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(piperidin-4-yloxy)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-5-methoxy-phenyl}-3-(4-pyrrolidin-1-yl-piperidin-1-yl)-5-trifluoromethyl-benzamide, 1-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-[4-(2-methyl-imidazol-1-yl)-3-trifluoromethyl-phenyl]-urea, 1-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-[4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-urea, pyridazine-4-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 2-chloro-N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-isonicotinamide, furan-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 1-methyl-1H-pyrrole-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 1H-imidazole-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-4-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-6-methyl-nicotinamide, 1-tert-butyl-5-methyl-1H-pyrazole-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, N-[4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, 3-(4-methyl-imidazol-1-yl)-N-(4-methyl-3-{1-6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-5-trifluoromethyl-benzamide, 4-methyl-N-[4-(2-methyl-imidazol-1-yl)-3-trifluoromethyl-phenyl]-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-(1-methyl-piperidin-4-yloxy)-5-trifluoromethyl-benzamide, pyrazine-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-methyl-pyrazine-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, quinoxaline-6-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-2-methyl-4-morpholin-4-ylmethyl-furan-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 2-benzyl-5-tert-butyl-2H-pyrazole-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(piperidin-4-ylamino)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(pyrrolidin-2-ylmethoxy)-5-rifluoromethyl-benzamide, 5-tert-butyl-2-methyl-furan-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-3-methyl-furan-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-2-diethylamino-furan-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-4-diethylamino-2-methyl-furan-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-thiophene-2-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 5-tert-butyl-3-methyl-furan-2-carboxylic acid (4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-amide, 5-tert-butyl-thiophene-2-carboxylic acid (4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-amide, 5-tert-butyl-2-methyl-furan-3-carboxylic acid (4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-amide, N-(3-{1-[6-(4-amino-cyclohexylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(piperidin-4-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[2-(4-methyl-piperazin-1-yl)-ethylamino]-pyrimidin-4-yl}-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-(3-{1-[6-(2,5-dimethyl-2H-pyrazol-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(2-methyl-2H-pyrazol-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(2,6-dimethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(2-methyl-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-piperazin-1-yl-5-trifluoromethyl-benzamide, N-{4-chloro-3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-fluoro-phenyl}-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-benzamide, N-{5-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-fluoro-phenyl}-benzamide, N-{5-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-benzamide, N-{4-chloro-3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-4-morpholin-4-ylmethyl-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-fluoro-phenyl}-4-morpholin-4-ylmethyl-3-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-4-morpholin-4-ylmethyl-3-trifluoromethyl-benzamide, N-{4-chloro-3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-fluoro-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{5-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-fluoro-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{5-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methoxy-phenyl}-benzamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzenesulfonamide, 3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-N-(3-trifluoromethyl-phenyl)-benzenesulfonamide, N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-fluoro-phenyl}-3-dimethylamino-5-trifluoromethyl-benzamide, N-{5-[-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-2-methyl-phenyl}-3-dimethylamino-5-trifluoromethyl-benzamide, N-{4-chloro-3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-dimethylamino-5-trifluoromethyl-benzamide, 3-(4-methyl-imidazol-1-yl)-N-(4-methyl-3-{1-[6-(pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-5-trifluoromethyl-benzamide, 4-(4-ethyl-piperazin-1-ylmethyl)-N-(4-methyl-3-{1-[6-(pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, 3-(4-ethyl-piperazin-1-yl)-N-(4-methyl-3-{1-[6-(pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-ylamino}-phenyl)-5-trifluoromethyl-benzamide, 4-chloro-N-(4-methyl-3-{1-[6-(pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-[3-(1-{6-[5-(4-ethyl-piperazin-1-yl)-pyridin-2-ylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-4-methyl-phenyl]-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(4-methyl-pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(4,6-dimethyl-pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, 6-(6-{2-[2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenylamino]-imidazol-1-yl}-pyrimidin-4-ylamino)-nicotinamide, N-(4-methyl-3-{1-[6-(5-methyl-pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(5-cyano-pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, 4-chloro-N-{3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, 4-chloro-N-(4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid (4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-amide, N-(3-{1-[6-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(3-morpholin-4-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(2-methoxy-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[2-(1-methyl-pyrrolidin-2-yl)-ethylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(pyridin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-pyrimidin-4-yl-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-pyrimidin-2-yl-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(4-methylamino-pyrimidin-2-yl)-1H-imidazol-2-ylamino]-phenyl}-3-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(2-methylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[4-(2-morpholin-4-yl-ethylamino)-pyrimidin-2-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[2-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(2-ethyl-2H-pyrazol-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(3-dimethylamino-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-{3-[1-(6-isopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide, N-[3-(1-{6-[(furan-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-4-methyl-phenyl]-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-[3-(1-{6-[(benzo[1,3]dioxol-5-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-4-methyl-phenyl]-3-trifluoromethyl-benzamide, N-(4-methyl-3-{-[6-(2-methyl-6-morpholin-4-yl-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(4-methyl-pyrimidin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(6-methoxy-pyridin-3-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-{4-methyl-3-[1-(6-morpholin-4-yl-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-phenyl}-3-trifluoromethyl-benzamide, N-(3-{1-[6-(4-ethyl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(3-fluoro-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(3-dimethylamino-ethyl-formamide-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(4-morpholin-4-yl-piperidin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[(thiazol-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-[4-methyl-3-(1-{6-[(6-methyl-pyrazin-2-ylmethyl)-amino]-pyrimidin-4-yl}-1H-imidazol-2-ylamino)-phenyl]-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(4-pyridin-2-yl-piperazin-1-yl)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(3-imidazol-1-yl-propylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, N-(4-methyl-3-{1-[6-(pyrazin-2-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-(3-{1-[6-(3-formamide-phenylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-4-methyl-phenyl)-3-trifluoromethyl-benzamide, 4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-N-(3-trifluoromethyl-phenyl)-benzamide, 4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-N-(3-trifluoromethyl-phenyl)-benzamide, N-(4-chloro-3-trifluoromethyl-phenyl)-4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(4-chloro-3-trifluoromethyl-phenyl)-4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, 1-tert-butyl-5-(4-methyl-piperazin-1-ylmethyl)-1H-pyrazole-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, 1-tert-butyl-5-morpholin-4-ylmethyl-1H-pyrazole-3-carboxylic acid {3-[1-(6-cyclopropylamino-pyrimidin-4-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-amide, N-(4-tert-butyl-thiazol-2-yl)-4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(4-tert-butyl-thiazol-2-yl)-4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(4-methyl-3-{1-[6-(4-methyl-piperazin-1-ylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-benzamide, N-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-4-methyl-3-{1-[6-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yl]-1H-imidazol-2-ylamino}-benzamide, N-(4-methyl-3-{1-[2-(2-morpholin-4-yl-ethylamino)-pyridin-4-yl]-1H-imidazol-2-ylamino}-phenyl)-3-trifluoromethyl-benzamide, N-{3-[1-(4-acetylamino-pyridin-2-yl)-1H-imidazol-2-ylamino]-4-methyl-phenyl}-3-trifluoromethyl-benzamide and 2-{2-[2-Methyl-5-(3 -trifluoromethyl-benzoylamino)-phenylamino]-imidazol-1-yl}-isonicotinamide.
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6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable excipient.
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7. A method for treating a disease in an animal in which inhibition of kinase activity can inhibit or ameliorate the pathology and/or symptomology of the kinase mediated disease, which method comprises administering to the animal a therapeutically effective amount of a compound of claim 1.
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8. The method of claim 5 in which the kinase is selected from the group consisting of Abl, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2α
- 2, MKK4, c-RAF, MKK6, SAPK2α
, and SAPK2β
.
- 2, MKK4, c-RAF, MKK6, SAPK2α
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9. The use of a compound of claim 1 in the manufacture of a medicament for treating a disease in an animal in which the kinase activity of Abl, BCR-Abl, PDGF-R, trkB, c-SRC, BMX, FGFR3, b-RAF, SGK, Tie2, Lck, JNK2α
- 2, MKK4, c-RAF, MKK6, SAPK2α and
/or SAPK2β
contributes to the pathology and/or symptomology of the disease.
- 2, MKK4, c-RAF, MKK6, SAPK2α and
-
2. The compound of claim 1 of Formula Ia:
Specification
- Resources
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Current AssigneeGreg Chopiuk, Guobao Zhang, Nathanael Schiander Gray, Novartis Ag, Pamela A. Albaugh, Pingda Ren, Qiang Ding, Qiong Zhang, Shuli You, Taebo Sim, Wang Xia
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Original AssigneeGreg Chopiuk, Guobao Zhang, Nathanael Schiander Gray, Pamela A. Albaugh, Pingda Ren, Qiang Ding, Qiong Zhang, Shuli You, Taebo Sim, Wang Xia
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InventorsDing, Qiang, Zhang, Guobao, Sim, Taebo, Ren, Pingda, Chopiuk, Greg, Zhang, Qiong, Wang, Xia, Albaugh, Pamela, Gray, Nathanael, You, Shull
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current514/235.800
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CPC Class CodesA61P 1/04 for ulcers, gastritis or re...A61P 1/16 for liver or gallbladder di...A61P 11/00 Drugs for disorders of the ...A61P 11/06 AntiasthmaticsA61P 13/08 of the prostateA61P 17/00 Drugs for dermatological di...A61P 17/06 AntipsoriaticsA61P 19/00 Drugs for skeletal disordersA61P 19/02 for joint disorders, e.g. a...A61P 19/10 for osteoporosisA61P 21/04 for myasthenia gravisA61P 25/00 Drugs for disorders of the ...A61P 25/16 Anti-Parkinson drugsA61P 25/28 for treating neurodegenerat...A61P 27/02 Ophthalmic agentsA61P 29/00 Non-central analgesic, anti...A61P 3/10 for hyperglycaemia, e.g. an...A61P 3/12 for electrolyte homeostasisA61P 35/00 Antineoplastic agentsA61P 35/02 specific for leukemiaA61P 35/04 : specific for metastasisA61P 37/00 : Drugs for immunological or ...A61P 37/02 : ImmunomodulatorsA61P 37/08 : Antiallergic agents antiast...A61P 43/00 : Drugs for specific purposes...A61P 5/14 : of the thyroid hormones, e....A61P 7/02 : Antithrombotic agents; Anti...A61P 9/00 : Drugs for disorders of the ...A61P 9/04 : Inotropic agents, i.e. stim...A61P 9/10 : for treating ischaemic or a...A61P 9/12 : AntihypertensivesA61P 9/14 : Vasoprotectives; Antihaemor...C07D 401/14 : containing three or more he...C07D 403/04 : directly linked by a ring-m...C07D 403/14 : containing three or more he...C07D 405/14 : containing three or more he...C07D 417/14 : containing three or more he...