Certain chemical entities, compositions, and methods
First Claim
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1. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula I:
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Abstract
Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.
54 Citations
22 Claims
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1. A method of treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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2. The method of claim 1, wherein the cancer is a cancer mediated by Raf.
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3. The method of claim 1, wherein R1, R2, and R3 are independently hydrogen, cyano, halo, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, or optionally substituted aminosulfonyl.
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4. The method of claim 3, wherein R1, R2, and R3 are independently hydrogen, cyano, or halo.
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5. The method of claim 1, wherein R1 and R2 are independently a halogen.
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6. The method of claim 5, wherein R1 and R2 are fluoro.
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7. The method of claim 1, wherein R4 is selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted aryl, and optionally substituted heteroaryl.
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8. The method of claim 7, wherein R4 is hydrogen.
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9. The method of claim 1, wherein R5 is —
- COR7, —
CO2R7, —
CONR7R8, —
C(NR9)NR7R8, or —
C(NCN)NR7R8, and wherein R7 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and
R8 and R9 are independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.
- COR7, —
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10. The method of claim 9, wherein R7 is optionally substituted alkyl, optionally substituted aryl, or optionally substituted heteroaryl;
- and R8 and R9 are independently hydrogen or optionally substituted alkyl.
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11. The method of claim 1, wherein R5 is COR7.
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12. The method of claim 11, wherein R7 is optionally substituted aryl.
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13. The method of claim 1, wherein R7 and R8 are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.
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14. The method of claim 1, wherein R4 and R5 are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.
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15. The method of claim 1, wherein Z1 is an optionally substituted bicyclic heteroaryl.
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16. The method of claim 1, wherein Z1 is 1,5-naphthyridin-2-yl, 1,7-naphthyridin-6-yl, 1H-pyrazolo[3,4-b]pyrazin-3-yl, 1H-pyrazolo[3,4-b]pyridin-3-yl, 5H-pyrrolo[2,3-b]pyrazin-7-yl, 7H-pyrrolo[2,3-c]pyridazin-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-5-yl, benzo[d]oxazol-5-yl, benzo[d]oxazol-6-yl, benzo[d]thiazol-6-yl, oxazolo[5,4-b]pyridin-5-yl, pyrido[3,4-b]pyrazin-7-yl, quinazolin-6-yl, or quinolin-6-yl.
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17. The method of claim 1, wherein Z1 is an optionally substituted quinolinyl.
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18. The method of claim 1, wherein Z1 is an optionally substituted quinazolinyl.
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19. The method of claim 1, wherein, for each occurrence, R6 is independently hydrogen, cyano, halo, hydroxy, carboxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted amino, optionally substituted acyl, optionally substituted aminocarbonyl, or optionally substituted aminosulfonyl.
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20. The method of claim 1, wherein, for each occurrence, R6 is independently hydrogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted alkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.
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21. The method of claim 1, wherein m is 0, 1, 2 or 3.
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22. The method of claim 1, wherein the compound is selected from the group consisting of:
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1-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-chlorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3,4-difluorophenyl)-3-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluorophenyl)-3-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-fluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]thiazole-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-cyanoquinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-chlorophenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(2,5-difluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(2,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(2,5-difluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]thiazole-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-chlorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-fluorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea, 1-(3-chloro-4-fluorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea, 1-(4-chlorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-chlorophenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(4-chlorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(4-chloro-3-fluorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea, 1-(3-chloro-4-fluorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea, 1-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea, 1-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea, 1-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3,4-difluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]thiazole-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-methylquinoline-6-carbonyl)phenyl)urea, 1-(3-(3-cyanoquinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(4-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)urea, 1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)urea, 1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)urea, 1-(3-(benzo[d]oxazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]oxazole-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(benzo[d]thiazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea, 1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea, 1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea, 1-(3,5-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea, 4-fluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide, 3,5-difluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 3-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 4-chloro-3-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, 4-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-methylquinoline-6-carbonyl)phenyl)benzamide, N-(3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, 3-fluoro-N-(3-fluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)benzamide, N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, 3-fluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 4-fluoro-N-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)benzamide, 3-fluoro-N-(3-fluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)benzamide, N-(3-(benzo[d]oxazole-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]thiazole-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(3-cyanoquinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-4-fluorobenzamide, 4-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, N-(2,5-difluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-4-fluorobenzamide, 4-chloro-N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, N-(2,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-4-fluorobenzamide, N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide, N-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide, N-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide, N-(2,5-difluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]thiazole-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-4-fluorobenzamide, 3-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, 4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, 4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)benzamide, N-(3,4-difluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-4-fluorobenzamide, 4-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, N-(3,4-difluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-4-fluorobenzamide, 4-chloro-N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, N-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-4-fluorobenzamide, N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide, N-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide, N-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide, N-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide, N-(3,4-difluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]thiazole-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-methylquinoline-6-carbonyl)phenyl)benzamide, N-(3-(3-cyanoquinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 3-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 4-chloro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)benzamide, N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide, 4-fluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3,4-difluoro-N-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 4-fluoro-N-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 4-fluoro-N-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)benzamide, 3-fluoro-N-(2,4,5-trifluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)benzamide, N-(3-(benzo[d]oxazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]oxazole-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(benzo[d]thiazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, and N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide.
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2. The method of claim 1, wherein the cancer is a cancer mediated by Raf.
Specification
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Current AssigneeNeuPharma, Inc.
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Original AssigneeNeuPharma, Inc.
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InventorsQian, Xiangping, Zhu, Yong-Liang
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Primary Examiner(s)Bakshi, Pancham
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Application NumberUS15/599,339Publication NumberTime in Patent Office894 DaysField of SearchUS Class CurrentCPC Class CodesA61J 1/03 for pills or tablets contai...A61J 1/05 for collecting, storing or ...A61K 2300/00 Mixtures or combinations of...A61K 31/47 Quinolines; IsoquinolinesA61K 31/517 ortho- or peri-condensed wi...A61K 45/06 Mixtures of active ingredie...A61P 35/00 Antineoplastic agentsC07D 215/14 Radicals substituted by oxy...C07D 239/74 with only hydrogen atoms, h...