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Details for Patent: 7,838,541

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Details for Patent: 7,838,541

Title:Aryl ureas with angiogenesis inhibiting activity
Abstract: This invention relates to methods of using aryl ureas to treat diseases mediated by the VEGF induced signal transduction pathway characterized by abnormal angiogenesis or hyperpermeability processes.
Inventor(s): Dumas; Jacques (Bethany, CT), Scott; William J. (Guilford, CT), Elting; James (Madison, CT), Hatoum-Makdad; Holia (Hamden, CT)
Assignee: Bayer Healthcare, LLC (Tarrytown, NY)
Filing Date:Feb 11, 2003
Application Number:10/361,858
Claims:1. A method for treating a disease in a human or other mammal wherein the disease that is treated is one or more of the following conditions: retinopathy and retinopathy of prematurity, comprising administering to a human or other mammal in need thereof the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyr- idyloxy)phenyl)urea of the formula below or a pharmaceutically acceptable salt thereof to regulate a VEGF-mediated signal transduction cascade, ##STR00012##

2. A method for treating a disease in a human or other mammal wherein the disease that is treated is one or more of the following conditions: retinopathy and retinopathy of prematurity, comprising administering to a human or other mammal in need thereof the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyr- idyloxy)phenyl)urea tosylate to regulate a VEGF-mediated signal transduction cascade.

3. A method of claim 1 wherein the compound of the formula VGFR, which is VEGF receptor-1 (fms-like tyrosine kinase-1(Flt-1)), VEGF receptor-2 (kinase insert domain containing receptor (KDR)); or VEGF receptor-3 (Flt-4).

4. A method of claim 3 wherein the inhibited VGFR is VEGF receptor-2 (KDR).

5. A method for treating a disease in a human or other mammal wherein the disease that is treated is one or more of the following conditions: retinopathy and retinopathy of prematurity, comprising administering to a human or other mammal in need thereof a compound which is TABLE-US-00011 N-[5-(tert-butyl)-2-(3-thienyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[4-(4-methoxyphenoxy)phenyl]amino}-N-[2-methoxy- 5-(trifluoromethyl)phenyl]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[5-(tert-butyl)-2-methoxyphenyl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[5-(tert-butyl)-2-(3-thienyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[3-(tert-butyl)phenyl]amino}-N-(4-(3- pyridyl)phenyl)carboxamide {[4-(4-methoxyphenoxy)phenyl]amino}-N-[2-methoxy- 5-(trifluoromethyl)phenyl]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]{[3-(2- methyl(4-pyridyloxy))phenyl]amino}carboxamide [(3-chloro-4-(6-quinolyloxy)phenyl)amino]-N-[2- methoxy-5-(trifluoromethyl)phenyl]carboxamide [(4-(4-pyridyloxy)phenyl)amino]-N-[3- (trifluoromethyl)phenyl]carboxamide N-[2-chloro-5-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[2-fluoro-5-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-(2- methyl-4-(3-pyridyloxy)phenyl)carboxamide N-[4-chloro-3-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[4-chloro-3-(trifluoromethyl)phenyl]{[4-(4- methoxyphenoxy)phenyl]amino}carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-[3-(4- pyridylcarbonyl)phenyl]carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-[3-(2- methyl(4-pyridyloxy))phenyl]carboxamide N-[4-fluoro-3-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl][(4- (4-pyridyloxy)phenyl)amino]carboxamide N-[5-methoxy-3-(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide [(3-bromo-4-chlorophenyl)amino]-N-(4-(4- pyridyloxy)phenyl)carboxamide [(4-(4-pyridyloxy)phenyl)amino]-N-[3- (trifluoromethoxy)phenyl]carboxamide N-[3,5-bis(trifluoromethyl)phenyl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(3- pyridyloxy)phenyl)amino]carboxamide {3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-[3-(2-methyl(4- pyridyloxy))phenyl]carboxamide N-[5-(tert-butyl)isoxazol-3-yl]{[4-(2-methyl(4- pyridyloxy))phenyl]amino}carboxamide 4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]pyridine-2- carboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide 4-[3-({N-[5-(tert-butyl)isoxazol-3- yl]carbamoyl}amino)phenoxy]pyridine-2-carboxamide 3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]benzamide N-[3-(methylethyl)isoxazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(3-cyclobutylisoxazol-5-yl)[(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(3-cyclobutylisoxazol-5-yl)[(4-(6- quinolyloxy)phenyl)amino]carboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[3-(tert-butyl)isoxazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)isoxazol-5-yl]{[4-(4- methoxyphenoxy)phenyl]amino}carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[3-(tert-butyl)pyrazol-5-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[3-(tert-butyl)pyrazol-5-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide {3-[4-({[3-(tert-butyl)pyrazol-5- yl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide, 2,2,2-trifluoroacetic acid N-[3-(tert-butyl)-1-methylpyrazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl]{[4-(4- pyridylmethoxy)phenyl]amino}carboxamide tert-butyl 3-(tert-butyl)-5-[({4-[3-(N- methylcarbamoyl)phenoxy]phenyl}amino)carbonylamino] pyrazolecarboxylate N-[5-(tert-butyl)(1,3,4-thiadiazol-2-yl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[5-(tert-butyl)(1,3,4-thiadiazol-2-yl)]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[5-(tert-butyl)(3-thienyl)][(4-(3- pyridyloxy)phenyl)amino]carboxamide N-[5-(tert-butyl)(3-thienyl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(6-chloro(1H-indazol-3-yl))[(4-(4- pyridyloxy)phenyl)amino]carboxamide ({4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-(1-methyl-3- phenylpyrazol-5-yl)carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[5-(tert-butyl)isoxazol-3-yl][(4-(3- pyridyloxy)phenyl)amino]carboxamide {3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-[3-(2-methyl(4- pyridyloxy))phenyl]carboxamide N-[5-(tert-butyl)isoxazol-3-yl]{[4-(2-methyl(4- pyridyloxy))phenyl]amino}carboxamide {4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy](2-pyridyl)}-N- methylcarboxamide 4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]pyridine-2- carboxamide 4-[3-({N-[5-(tert-butyl)isoxazol-3- yl]carbamoyl}amino)phenoxy]pyridine-2-carboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide 3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]benzamide {4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)-3-chlorophenoxy](2- pyridyl)}-N-methylcarboxamide {3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]phenyl}-N-(2- morpholin-4-ylethyl)carboxamide {4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy](2-pyridyl)}-N- ethylcarboxamide {4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)-2-chlorophenoxy](2- pyridyl)}-N-methylcarboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-{2-methyl-4-[2- (N-methylcarbamoyl)(4- pyridyloxy)]phenyl}carboxamide {[5-(tert-butyl)isoxazol-3-yl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {3-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenoxy]phenyl}-N-(3- pyridyl)carboxamide {4-[4-({[5-(tert-butyl)isoxazol-3- yl]amino}carbonylamino)phenylthio](2-pyridyl)}-N- methylcarboxamide N-methyl{4-[4-({[3-(methylethyl)isoxazol-5- yl]amino}carbonylamino)phenoxy](2- pyridyl)}carboxamide N-methyl{4-[3-({[3-(methylethyl)isoxazol-5- yl]amino}carbonylamino)phenoxy](2- pyridyl)}carboxamide N-(3-cyclobutylisoxazol-5-yl)[(4-(6- quinolyloxy)phenyl)amino]carboxamide N-(3-cyclobutylisoxazol-5-yl)[(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)isoxazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)isoxazol-5-yl]{[4-(4- methoxyphenoxy)phenyl]amino}carboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[3-(tert-butyl)isoxazol-5-yl]{[4-(1,3-dioxoisoindolin- 5-yloxy)phenyl]amino}carboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-[4-(1- oxoisoindolin-5-yloxy)phenyl]carboxamide {4-[4-({[3-(tert-butyl)isoxazol-5- yl]amino}carbonylamino)phenoxy](2-pyridyl)}-N- ethylcarboxamide {4-[4-({[3-(tert-butyl)isoxazol-5- yl]amino}carbonylamino)-2-chlorophenoxy](2- pyridyl)}-N-methylcarboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {4-[4-({[3-(tert-butyl)isoxazol-5- yl]amino}carbonylamino)phenylthio](2-pyridyl)}-N- methylcarboxamide {4-[4-({[3-(tert-butyl)isoxazol-5- yl]amino}carbonylamino)phenoxy](2-pyridyl)}-N- methylcarboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-[3-(6-methyl(3- pyridyloxy))phenyl]carboxamide N-[3-(tert-butyl)isoxazol-5-yl][(6-(4-pyridylthio)(3- pyridyl))amino]carboxamide {[3-(tert-butyl)isoxazol-5-yl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl]({4-[2-(N- methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)carboxamide N-[3-(1,1-dimethylpropyl)isoxazol-5-yl]{[4-(2-methyl(4- pyridylthio))phenyl]amino}carboxamide N-[3-(tert-butyl)pyrazol-5-yl]{[4-(6-methyl(3- pyridyloxy))phenyl]amino}carboxamide {[3-(tert-butyl)pyrazol-5-yl]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[3-(tert-butyl)pyrazol-5-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide {3-[4-({[3-(tert-butyl)pyrazol-5- yl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide, 2,2,2-trifluoroacetic acid N-[3-(tert-butyl)-1-methylpyrazol-5-yl]{[4-(4- pyridylmethoxy)phenyl]amino}carboxamide {5-[4-({[3-(tert-butyl)-1-methylpyrazol-5- yl]amino}carbonylamino)phenoxy]-2-methoxyphenyl}- N-methylcarboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl][(4-(4-

pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-methylpyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide tert-butyl 3-(tert-butyl)-5-[({4-[3-(N- methylcarbamoyl)phenoxy]phenyl}amino)carbonylamino] pyrazolecarboxylate N-[5-(tert-butyl)(1,3,4-thiadiazol-2-yl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide {[5-(tert-butyl)(1,3,4-thiadiazol-2-yl)]amino}-N-(3-(4- pyridylthio)phenyl)carboxamide N-[5-(tert-butyl)(1,3,4-thiadiazol-2-yl)]{[6-(6-methyl(3- pyridyloxy))(3-pyridyl)]amino}carboxamide N-[5-(1,1-dimethylpropyl)(1,3,4-thiadiazol-2-yl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[5-(1,1-dimethylpropyl)(1,3,4-thiadiazol-2-yl)][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[5-(tert-butyl)(3-thienyl)][(4-(3- pyridyloxy)phenyl)amino]carboxamide {3-[4-({[5-(tert-butyl)(1,3,4-oxadiazol-2- yl)]amino}carbonylamino)phenoxy]phenyl}-N- ethylcarboxamide {3-[4-({[5-(tert-butyl)(1,3,4-oxadiazol-2- yl)]amino}carbonylamino)phenoxy]phenyl}-N- (methylethyl)carboxamide {3-[4-({[5-(tert-butyl)(1,3,4-oxadiazol-2- yl)]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide N-[5-(tert-butyl)(1,3,4-oxadiazol-2-yl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(3-cyclopropyl-1-methylpyrazol-5-yl)[(4-(6- quinolyloxy)phenyl)amino]carboxamide ({4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-(1-methyl-3- phenylpyrazol-5-yl)carboxamide N-[2-(tert-butyl)(1,3-thiazol-5-yl)]{[4-(6-methyl(3- pyridyloxy))phenyl]amino}carboxamide [(2,3-dichlorophenyl)amino]-N-[3-(tert-butyl)-1-phenylpyrazol- 5-yl]carboxamide N-[1-(4-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(2,3- dichlorophenyl)amino]carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(2,3- dichlorophenyl)amino]carboxamide N-[3-(3-(tert-butyl)-5-{[(4-phenoxyphenyl) amino]carbonylamino}pyrazolyl)phenyl]acetamide N-[1-(2,6-dichlorophenyl)-3-(tert-butyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(4-fluorophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(2-methylphenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(3-fluorophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-{3-(tert-butyl)-1-[4-(methylsulfonyl)phenyl]pyrazol-5- yl}{[4-(4-pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(4-nitrophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(3-methoxyphenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-(3-fluorophenyl)pyrazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-(4-fluorophenyl)pyrazol-5-yl][(3-(4- pyridylthio)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-(3-fluorophenyl)pyrazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-[3-(tert-butyl)-1-(4-fluorophenyl)pyrazol-5-yl][(4-(4- pyridyloxy)phenyl)amino]carboxamide [(2,3-dichlorophenyl)amino]-N-[3-(tert-butyl)-1-phenylpyrazol- 5-yl]carboxamide N-[1-(4-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(2,3- dichlorophenyl)amino]carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(2,3- dichlorophenyl)amino]carboxamide N-[3-(3-(tert-butyl)-5-{[(4-phenoxyphenyl) amino]carbonylamino}pyrazolyl)phenyl]acetamide N-[1-(2,6-dichlorophenyl)-3-(tert-butyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(4-fluorophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(2-methylphenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(3-fluorophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-{3-(tert-butyl)-1-[4-(methylsulfonyl)phenyl]pyrazol-5- yl}{[4-(4-pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(4-nitrophenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[3-(tert-butyl)-1-(3-methoxyphenyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl]{[4-(4- pyridylmethyl)phenyl]amino}carboxamide N-[1-(3-aminophenyl)-3-(tert-butyl)pyrazol-5-yl][(4-(4- pyridylthio)phenyl)amino]carboxamide {3-[4-({[3-(tert- butyl)phenyl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide 4-[3-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]pyridine-2- carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide 4-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]pyridine-2- carboxamide {4-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)-3- methylphenoxy](2-pyridyl)}-N-methylcarboxamide ({2-chloro-4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide ({4-[2-(N-ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)-N-[2- methoxy-5-(trifluoromethyl)phenyl]carboxamide ({3-chloro-4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide 3-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]benzamide ({4-[2-(N,N-dimethylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(4-{5-[N-(2- morpholin-4-ylethyl)carbamoyl](3- pyridyloxy)}phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[5-(N- methylcarbamoyl)(3-pyridyloxy)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[3-(N-(3- pyridyl)carbamoyl)phenoxy]phenyl}amino)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-methylcarboxamide 4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]pyridine- 2-carboxamide 4-[3-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]pyridine- 2-carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{2-methyl-4- [2-(N-methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {4-[3-chloro-4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-methylcarboxamide N-[4-chloro-3-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide {3-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]phenyl}- N-(2-morpholin-4-ylethyl)carboxamide {3-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]phenyl}- N-(2-piperidylethyl)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenylthio](2- pyridyl)}-N-methylcarboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-morpholin-4-ylethyl)carboxamide {5-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](3- pyridyl)}-N-methylcarboxamide N-[4-chloro-3-(trifluoromethyl)phenyl]({4-[3-(N-(3- pyridyl)carbamoyl)phenoxy]phenyl}amino)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-hydroxyethyl)carboxamide {4-[4-({[4-bromo-3- (trifluoromethyl)phenyl]amino}carbonylamino)-2- chlorophenoxy](2-pyridyl)}-N-methylcarboxamide N-[4-bromo-3-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{4-methyl-3- [2-(N-methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {4-[4-({[4-bromo-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-morpholin-4-ylethyl)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({2-chloro- 4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({3-chloro- 4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide {3-[4-({[3-(tert- butyl)phenyl]amino}carbonylamino)phenoxy]phenyl}-N- methylcarboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide 4-[3-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]pyridine-2- carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide 4-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]pyridine-2- carboxamide {4-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)-3- methylphenoxy](2-pyridyl)}-N-methylcarboxamide ({2-chloro-4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide ({4-[2-(N-ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)-N-[2- methoxy-5-(trifluoromethyl)phenyl]carboxamide ({3-chloro-4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide 3-[4-({N-[2-methoxy-5- (trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]benzamide ({4-[2-(N,N-dimethylcarbamoyl)(4- pyridyloxy)]phenyl}amino)-N-[2-methoxy-5- (trifluoromethyl)phenyl]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl][(4-{5-[N-(2- morpholin-4-ylethyl)carbamoyl](3- pyridyloxy)}phenyl)amino]carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[5-(N- methylcarbamoyl)(3-pyridyloxy)]phenyl}amino)carboxamide N-[2-methoxy-5-(trifluoromethyl)phenyl]({4-[3-(N-(3- pyridyl)carbamoyl)phenoxy]phenyl}amino)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-methylcarboxamide 4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]pyridine- 2-carboxamide 4-[3-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]pyridine- 2-carboxamide

{[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{2-methyl-4- [2-(N-methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {4-[3-chloro-4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-methylcarboxamide N-[4-chloro-3-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide {3-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]phenyl}- N-(2-morpholin-4-ylethyl)carboxamide {3-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy]phenyl}- N-(2-piperidylethyl)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenylthio](2- pyridyl)}-N-methylcarboxamide {[4-chloro-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-morpholin-4-ylethyl)carboxamide {5-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](3- pyridyl)}-N-methylcarboxamide N-[4-chloro-3-(trifluoromethyl)phenyl]({4-[3-(N-(3- pyridyl)carbamoyl)phenoxy]phenyl}amino)carboxamide {4-[4-({[4-chloro-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-hydroxyethyl)carboxamide {4-[4-({[4-bromo-3- (trifluoromethyl)phenyl]amino}carbonylamino)-2- chlorophenoxy](2-pyridyl)}-N-methylcarboxamide N-[4-bromo-3-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{4-methyl-3- [2-(N-methylcarbamoyl)(4-pyridyloxy)]phenyl}carboxamide {[4-bromo-3-(trifluoromethyl)phenyl]amino}-N-{3-[2-(N- methylcarbamoyl)(4-pyridylthio)]phenyl}carboxamide {4-[4-({[4-bromo-3- (trifluoromethyl)phenyl]amino}carbonylamino)phenoxy](2- pyridyl)}-N-(2-morpholin-4-ylethyl)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({2-chloro- 4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({3-chloro- 4-[2-(N-methylcarbamoyl)(4- pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({3-[2-(N- methylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide N-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]({4-[2-(N- ethylcarbamoyl)(4-pyridyloxy)]phenyl}amino)carboxamide [(4-fluorophenyl)amino]-N-(3-isoquinolyl)carboxamide N-(2-methoxy(3-quinolyl))[(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(2-methoxy(3-quinolyl))[(3-(4- pyridylthio)phenyl)amino]carboxamide N-[1-(4-methylpiperazinyl)(3-isoquinolyl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(2-methoxy(3-quinolyl))[(4-(4- pyridyloxy)phenyl)amino]carboxamide N-(2-methoxy(3-quinolyl))[(3-(4- pyridylthio)phenyl)amino]carboxamide N-[1-(4-methylpiperazinyl)(3-isoquinolyl)][(4-(4- pyridyloxy)phenyl)amino]carboxamide

or a pharmaceutically acceptable salt thereof to regulate a VEGF-mediated signal transduction cascade.
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