Substituted pyridine derivatives useful in the treatment of cancer and other disorders

6) A compound which is

• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(hydrazinocarbonyl)pyridin-4-yl]oxy}phenyl)urea
• N-(4-{[2-(hydrazinocarbonyl)pyridin-4-yl]oxy}phenyl)-N′-(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[3-({2-[(2,2-dimethylhydrazino)carbonyl]pyridin-4-yl}oxy)phenyl]urea
• 4-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-piperidin-1-ylpyridine-2-carboxamide
• N-piperidin-1-yl-4-[3-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboxamide
• 4-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-morpholin-4-ylpyridine-2-carboxamide
• N-morpholin-4-yl-4-[3-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboxamide
• 4-[3-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-morpholin-4-ylpyridine-2-carboxamide
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(1H-tetrazol-5-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(4,5-dihydro-1H-imidazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(4-methyl-1,3-thiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-quinolin-6-yl-N′-(4-{[2-(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-(4-{[2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)-N′-(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)urea
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboximidamide
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}pyridine-2-carboximidamide
• N-methyl-4-[4-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboximidamide
• N-methyl-4-(4-{[(quinolin-6-ylamino)carbonyl]amino}phenoxy)pyridine-2-carboximidamide
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}pyridine-2-carbothioamide
• 4-(4-{[(quinolin-6-ylamino)carbonyl]amino}phenoxy)pyridine-2-carbothioamide or
• 4-[4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carbothioamide

17) A method for treating or preventing diseases mediated by the VEGF-induced signal transduction pathway comprising administering a compound selected from the group consisting of:

• 4-{4-[3-(4-Chloro-3-trifluoromethyl-phenyl)-ureido]-phenoxy}-pyridine-2-carbothioic acid amide;
• 4-{3-[3-(2,2,4,4-Tetrafluoro-4H-benzo[1,3]dioxin-6-yl)-ureido]-phenoxy}-pyridine-2-carboxylic acid (1-piperidyl)-amide;
• 4-{3-[3-(2,2,4,4-Tetrafluoro-4H-benzo[1,3]dioxin-6-yl)-ureido]-phenoxy}-pyridine-2-carboxylic acid (4-morpholino)-amide;
• 4-{3-[3-(1-Methyl-1H-indazol-5-yl)-ureido]-phenoxy}-pyridine-2-carboxylic acid (4-morpholino)-amide;
• 4-{4-[3-(4-Chloro-3-trifluoromethyl-phenyl)-ureido]-phenoxy}-pyridine-2-carboxamidine;
• 1-(4-Chloro-3-trifluoromethyl-phenyl)-3-{4-[2-(1H-tetrazol-5-yl)-pyridinyl-4-oxy]-phenyl}-urea;
• 1-(4-Chloro-3-trifluoromethyl-phenyl)-3-{4-[2-(4,5-dihydro-1H-imidazol-2-yl)-pyridinyl-4-oxy]-phenyl}-urea;
• 4-{4-[3-(4-Chloro-3-trifluoromethyl-phenyl)-ureido]-phenoxy}-N-methyl-pyridine-2-carboxamidine;
• or a salt form, prodrug or metabolite thereof.

18) A method for treating or preventing cancer comprising administering a compound selected from the group consisting of:

• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(hydrazinocarbonyl)pyridin-4-yl]oxy}phenyl)urea
• N-(4-{[2-(hydrazinocarbonyl)pyridin-4-yl]oxy}phenyl)-N′-(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-[3-({2-[(2,2-dimethylhydrazino)carbonyl]pyridin-4-yl}oxy)phenyl]urea
• 4-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-piperidin-1-ylpyridine-2-carboxamide
• N-piperidin-1-yl-4-[3-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboxamide
• 4-{3-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-morpholin-4-ylpyridine-2-carboxamide
• N-morpholin-4-yl-4-[3-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboxamide
• 4-[3-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]-N-morpholin-4-ylpyridine-2-carboxamide
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(1H-tetrazol-5-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(4,5-dihydro-1H-imidazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(4-methyl-1,3-thiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-quinolin-6-yl-N′-(4-{[2-(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-[4-chloro-3-(trifluoromethyl)phenyl]-N′-(4-{[2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)urea
• N-(4-{[2-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyridin-4-yl]oxy}phenyl)-N′-(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)urea
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboximidamide
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}pyridine-2-carboximidamide
• N-methyl-4-[4-({[(2,2,4,4-tetrafluoro-4H-1,3-benzodioxin-6-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carboximidamide
• N-methyl-4-(4-{[(quinolin-6-ylamino)carbonyl]amino}phenoxy)pyridine-2-carboximidamide
• 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}pyridine-2-carbothioamide
• 4-(4-{[(quinolin-6-ylamino)carbonyl]amino}phenoxy)pyridine-2-carbothioamide
• 4-[4-({[(1-methyl-1H-indazol-5-yl)amino]carbonyl}amino)phenoxy]pyridine-2-carbothioamide,
• or a salt form, prodrug or metabolite thereof.

27) A compound of formula (I)

• or a pharmaceutically acceptable salt, wherein A is phenyl, naphthyl, indazolyl, quinolinyl, pyridyl, benzo[1,3]dioxolan-5-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl or 4H-benzo[1,3]dioxin-6-yl, optionally substituted with 1-4 substituents which are independently R1 and halogen,
• L is —O— and B is phenyl, optionally substituted with 1-4 halogen;
• M is a pyridine ring, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, or nitro;
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• (3) tetrazolyl;
• (4) imidazolyl;
• (5) imidazoline-2-yl;
• (6) 1,3,4-oxadiazoline-2-yl;
• (7) 1,3-thiazoline-2-yl;
• (8) 5-thioxo-4,5-dihydro-1,3,4-thiazoline-2-yl;
• (9) 5-oxo-4,5-dihydro-1,3,4-oxadiazoline-2-yl;
• or
• (10) a group of the formula
• wherein each of R1, R2, R3, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is tetrahydropyrane, tetrahydrofurane, 1,3-dioxolane, 1,4-dioxane, morpholine, thiomorpholine, piperazine, piperidine, piperidinone, tetrahydropyrimidone, pentamethylene sulfide, tetramethylene sulfide, dihydropyrane, dihydrofurane, dihydrothiophene, pyrrole, furan, thiophene, imidazole, pyrazole, thiazole, oxazole, isoxazole, isothiazole, triazole, pyridine, pyrimidine, pyridazine, pyrazine, triazine or benzoxazole, indazole, quinoline, quinazoline, imidazopyrimidine or naphtyridine;
• R4 and R5 may additionally be taken together to form a 5 or 6 membered aliphatic ring, which may be interrupted by an atom selected from N, O or S, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, up to perhalo substituted C1-C5 linear or branched alkyl, C1-C3 alkoxy, hydroxy, oxo, carboxy, amino, C1-C3 alkylamino, C1-C6dialkylamino, halogen, cyano, or nitro;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) cyano,
• (d) nitro,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —C(O)R7, where R7 is C1-C5 linear, branched, or cyclic alkyl;
• R7 is hydrogen or linear, branched, or cyclic C1-C5 alkyl;
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.

28) A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein
• A is
• wherein A is optionally substituted with 1-4 substituents which are independently R1, OR1, S(O)pR1, C(O)R1, C(O)OR1, C(O)NR1R2, halogen, hydroxy, oxide, amino, cyano, or nitro;
• B is phenyl, or pyridyl, optionally substituted with 1-4 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, cyano, or nitro;
• L is
• (a) —(CH2)m—O—(CH2)l—,
• (b) —(CH2)m—(CH2)l—,
• (c) —(CH2)m—C(O)—(CH2)l—,
• (d) —(CH2)m—NR3—(CH2)l—,
• (e) —(CH2)m—NR3C(O)—(CH2)l—,
• (f) —(CH2)m—S—(CH2)l—,
• (g) —(CH2)m—C(O)NR3—(CH2)l—, or
• (h) a single bond;
• m and l are integers independently selected from 0-4;
• M is a pyridine ring, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, or nitro;
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• (3) tetrazolyl;
• (4) imidazolyl;
• (5) imidazoline-2-yl;
• (6) 1,3,4-oxadiazoline-2-yl;
• (7) 1,3-thiazoline-2-yl;
• (8) 5-thioxo-4,5-dihydro-1,3,4-thiazoline-2-yl;
• (9) 5-oxo-4,5-dihydro-1,3,4-oxadiazoline-2-yl;
• or
• (10) a group of the formula
• wherein each of R1, R2, R3, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is a tetrahydropyrane, tetrahydrofurane, 1,3-dioxolane, 1,4-dioxane, morpholine, thiomorpholine, piperazine, piperidine, piperidinone, tetrahydropyrimidone, pentamethylene sulfide, tetramethylene sulfide, dihydropyrane, dihydrofurane, dihydrothiophene, pyrrole, furan, thiophene, imidazole, pyrazole, thiazole, oxazole, isoxazole, isothiazole, triazole, pyridine, pyrimidine, pyridazine, pyrazine, triazine or benzoxazole, indazole, quinoline, quinazoline, imidazopyrimidine or naphtyridine;
• R4 and R5 may additionally be taken together to form a 5 or 6 membered aliphatic ring, which may be interrupted by an atom selected from N, O or S, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, up to perhalo substituted C1-C5 linear or branched alkyl, C1-C3 alkoxy, hydroxy, oxo, carboxy, amino, C1-C3 alkylamino, C1-C6dialkylamino, halogen, cyano, or nitro;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) cyano,
• (d) nitro,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —C(O)R7, where R7 is C1-C5 linear, branched, or cyclic alkyl;
• R7 is hydrogen or linear, branched, or cyclic C1-C5 alkyl;
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.

32) A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein
• A is
• wherein A is optionally substituted with 1-4 substituents which are independently R1, OR1, or halogen
• B is phenyl or pyridinyl, optionally substituted with 1-4 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, cyano, or nitro,
• L is —O—,
• M is a pyridine ring,
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• (3) tetrazolyl;
• (4) imidazolyl;
• (5) imidazoline-2-yl;
• (6) 1,3,4-oxadiazoline-2-yl;
• (7) 1,3-thiazoline-2-yl;
• (8) 5-thioxo-4,5-dihydro-1,3,4-thiazoline-2-yl;
• (9) 5-oxo-4,5-dihydro-1,3,4-oxadiazoline-2-yl;
• or
• (10) a group of the formula
• wherein each of R1, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is a tetrahydropyrane, tetrahydrofurane, 1,3-dioxolane, 1,4-dioxane, morpholine, thiomorpholine, piperazine, piperidine, piperidinone, tetrahydropyrimidone, pentamethylene sulfide, tetramethylene sulfide, dihydropyrane, dihydrofurane, dihydrothiophene, pyrrole, furan, thiophene, imidazole, pyrazole, thiazole, oxazole, isoxazole, isothiazole, triazole, pyridine, pyrimidine, pyridazine, pyrazine, triazine or benzoxazole, indazole, quinoline, quinazoline, imidazopyrimidine or naphtyridine;
• R4 and R5 may additionally be taken together to form a 5 or 6 membered aliphatic ring, which may be interrupted by an atom selected from N, O or S, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, up to perhalo substituted C1-C5 linear or branched alkyl, C1-C3 alkoxy, hydroxy, oxo, carboxy, amino, C1-C3 alkylamino, C1-C6dialkylamino, halogen, cyano, or nitro;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) cyano,
• (d) nitro,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —C(O)R7, where R7 is C1-C5 linear, branched, or cyclic alkyl;
• R7 is hydrogen or linear, branched, or cyclic C1-C5 alkyl;
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.

37) A compound of formula (I)

• or a pharmaceutically acceptable salt, wherein
• A is phenyl;
• optionally substituted with 1-4 substituents which are independently R1, OR1, S(O)pR1, C(O)R1, C(O)OR1, C(O)NR1R2, halogen, hydroxy, oxide, amino, cyano, or nitro;
• L is —O— and B is phenyl, optionally substituted with 1-4 halogen;
• M is a pyridine ring, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, or nitro;
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• or
• (3) a group of the formula
• wherein each of R1, R2, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is pyridine;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl, or
• (c) up to per-halo substituted C1-C5 linear or branched alkyl, or
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.

38) A compound of formula (I)

• or a pharmaceutically acceptable salt, wherein
• A is pyridine optionally substituted with 1-4 substituents which are independently R1, OR1, S(O)pR1, C(O)R1, C(O)OR1, C(O)NR1R2, halogen, hydroxy, oxide, amino, cyano, or nitro;
• L is —O— and B is phenyl, optionally substituted with 1-4 halogen;
• M is a pyridine ring, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, or nitro;
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• or
• (3) a group of the formula
• wherein each of R1, R2, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is pyridine;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl, or
• (c) up to per-halo substituted C1-C5 linear or branched alkyl, or
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.

39) A compound of formula (I)

• or a pharmaceutically acceptable salt, wherein
• A is pyrazole optionally substituted with 1-4 substituents which are independently R1, OR1, S(O)pR1, C(O)R1, C(O)OR1, C(O)NR1R2, halogen, hydroxy, oxide, amino, cyano, or nitro;
• L is —O— and B is phenyl, optionally substituted with 1-4 halogen;
• M is a pyridine ring, optionally substituted with 1-3 substituents which are independently C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl, C1-C3 alkoxy, hydroxy, oxide, amino, C1-C3 alkylamino, C1-C6 dialkylamino, halogen, or nitro;
• Q is:
• (1) C(S)NR4R5;
• (2) C(O)NR7—NR4R5;
• or
• (3) a group of the formula
• wherein each of R1, R2, R4 and R5 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl,
• (c) phenyl,
• (d) C1-C3 phenyl-alkyl,
• (e) up to per-halo substituted C1-C5 linear or branched alkyl, or
• (f) —(CH2)q—X, where X is pyridine;
• R6 is independently
• (a) hydrogen,
• (b) C1-C5 linear, branched, or cyclic alkyl, or
• (c) up to per-halo substituted C1-C5 linear or branched alkyl, or
• q is an integer 0, 1, 2, 3, or 4 and
• p is an integer 0, 1, or 2.