CA2549558A1 - Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors - Google Patents
Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors Download PDFInfo
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- CA2549558A1 CA2549558A1 CA002549558A CA2549558A CA2549558A1 CA 2549558 A1 CA2549558 A1 CA 2549558A1 CA 002549558 A CA002549558 A CA 002549558A CA 2549558 A CA2549558 A CA 2549558A CA 2549558 A1 CA2549558 A1 CA 2549558A1
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
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- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
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- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
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- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C275/36—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with at least one of the oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. N-aryloxyphenylureas
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- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
Claims (65)
1. A compound of Formula I:
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-, A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q , where L is a 5 or 6 membered cyclic structure bound directly to D, L1 comprises a substituted cyclic moiety having at least 5 members, M is a bridging group having at least one atom, q is an integer of from 1-3; and each cyclic structure of L and L1 contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, and B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y) R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, R z is hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and D and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, - (CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-, -CHX a-, -CX a2-, -S-(CH2)m- and -N(R7) (CH2)m-, where m = 1-3, and X a is halogen; and Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O) R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7, with R7 as defined above;
with a proviso that the compound is not a compound selected from the group consisting of:
N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N- ( 4-bromo-3- (trifluoromethyl ) phenyl ) -N' - ( 3- (2- (N-methylcarbamoyl)-4-pyridylthio)phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, or a pharmaceutically acceptable salt thereof.
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-, A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q , where L is a 5 or 6 membered cyclic structure bound directly to D, L1 comprises a substituted cyclic moiety having at least 5 members, M is a bridging group having at least one atom, q is an integer of from 1-3; and each cyclic structure of L and L1 contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, and B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y) R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, R z is hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and D and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted, the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, - (CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-, -CHX a-, -CX a2-, -S-(CH2)m- and -N(R7) (CH2)m-, where m = 1-3, and X a is halogen; and Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O) R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7, with R7 as defined above;
with a proviso that the compound is not a compound selected from the group consisting of:
N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, N- ( 4-bromo-3- (trifluoromethyl ) phenyl ) -N' - ( 3- (2- (N-methylcarbamoyl)-4-pyridylthio)phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(4-bromo-3-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl)urea, or a pharmaceutically acceptable salt thereof.
2. A compound as in claim 1 wherein:
Ry is hydrogen, C1-to alkyl, C1_lo alkoxy, C3-to cycloalkyl having 0-3 heteroatoms, CZ-to alkenyl, C1-Zo alkenoyl, C6_12 aryl, C3_12 hetaryl having 1-3 heteroatoms selected from N, S and 0, C~_z4 aralkyl, C~_z9 alkaryl, substituted C1-to alkyl, substituted C1-to alkoxy, substituted Cs-to cycloalkyl having 0-3 heteroatoms selected from N, S and 0, substituted C6-C19 aryl, substituted C3_12 hetaryl having 1-3 heteroatoms selected from N, S and 0, substituted C~_29 alkaryl or substituted C~_24 aralkyl, where Ry is a substituted group, it is substituted by halogen up to per halo, 91a R2 is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-3 heteroatoms, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-C12 hetaryl having 1-3 heteroatoms selected from S, N and O, C7-24 alkaryl, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C6-C14 aryl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from S, N and O, substituted C3-12 hetaryl having 1-3 heteroatoms selected from S, N and O, substituted C7-24 alkaryl or substituted C7-24 aralkyl where R z is a substituted group, it is substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 91b alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl up to per halo cycloalkyl having 0-3 heteroatoms selected from N, S and O, halo substituted C3-C12 hetaryl up to per halo hetaryl having 1-3 heteroatoms selected from O, N and S, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)Rg, R a and R b are, a) independently hydrogen, a carbon based moiety selected from to group consisting of C1-C10 alkyl, C1-C10 alkoxy, C3-10cycloalkyl, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-12 hetaryl having 1-3 heteroatoms selected from O, N and S, C3-12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, C7-12 aralkyl, C7-C24 alkaryl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C3-10 cycloalkyl, having 0-3 heteroatoms selected from N, S and O, substituted C6-12 aryl, substituted C3-12 hetaryl having 1-3 heteroatoms selected from N, S
and O, substituted C7-24 aralkyl, substituted C7-24 alkaryl, where R a and R b are a substituted group, they are substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g; or -OSi(R f)3 where R f is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-12 aryl, C3-C12 hetaryl having 1-3 heteroatoms selected from O, S and N, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-C10 alkoxy, substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, substituted C3-C12 heteraryl having 1-3 hetervatoms selected from O, S, and N, substituted C6-12 aryl, and substituted C7-24 alkaryl, where R f is a substituted group it is substituted halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl. C7 -C24 alkaryl, C7 -C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O with substituents selected from the group consisting of halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C7 -C24 alkaryl, C7 -C24 aralkyl, halo substituted C1-6 alkyl up to per halo alkyl, halo substituted C6-C12 aryl up to per halo aryl, halo substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, or c)- one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-alkoxy, C6-12 aryl, C7 -C24 alkaryl, C7 -C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, where R g is C1-10 alkyl; -CN, -CO2R d, -OR d, -SR d, -NO2, -C(O) R c. -NR d R
c. -NR j C(O)OR e and -NR d C(O)R e, and R d and R e are independently selected from the group consisting of hydrogen, C1-10, alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-
Ry is hydrogen, C1-to alkyl, C1_lo alkoxy, C3-to cycloalkyl having 0-3 heteroatoms, CZ-to alkenyl, C1-Zo alkenoyl, C6_12 aryl, C3_12 hetaryl having 1-3 heteroatoms selected from N, S and 0, C~_z4 aralkyl, C~_z9 alkaryl, substituted C1-to alkyl, substituted C1-to alkoxy, substituted Cs-to cycloalkyl having 0-3 heteroatoms selected from N, S and 0, substituted C6-C19 aryl, substituted C3_12 hetaryl having 1-3 heteroatoms selected from N, S and 0, substituted C~_29 alkaryl or substituted C~_24 aralkyl, where Ry is a substituted group, it is substituted by halogen up to per halo, 91a R2 is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-3 heteroatoms, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-C12 hetaryl having 1-3 heteroatoms selected from S, N and O, C7-24 alkaryl, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C6-C14 aryl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from S, N and O, substituted C3-12 hetaryl having 1-3 heteroatoms selected from S, N and O, substituted C7-24 alkaryl or substituted C7-24 aralkyl where R z is a substituted group, it is substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 91b alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl up to per halo cycloalkyl having 0-3 heteroatoms selected from N, S and O, halo substituted C3-C12 hetaryl up to per halo hetaryl having 1-3 heteroatoms selected from O, N and S, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)Rg, R a and R b are, a) independently hydrogen, a carbon based moiety selected from to group consisting of C1-C10 alkyl, C1-C10 alkoxy, C3-10cycloalkyl, C2-10 alkenyl, C1-10 alkenoyl, C6-12 aryl, C3-12 hetaryl having 1-3 heteroatoms selected from O, N and S, C3-12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, C7-12 aralkyl, C7-C24 alkaryl, substituted C1-10 alkyl, substituted C1-10 alkoxy, substituted C3-10 cycloalkyl, having 0-3 heteroatoms selected from N, S and O, substituted C6-12 aryl, substituted C3-12 hetaryl having 1-3 heteroatoms selected from N, S
and O, substituted C7-24 aralkyl, substituted C7-24 alkaryl, where R a and R b are a substituted group, they are substituted by halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g; or -OSi(R f)3 where R f is hydrogen, C1-10 alkyl, C1-10 alkoxy, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-12 aryl, C3-C12 hetaryl having 1-3 heteroatoms selected from O, S and N, C7-24 aralkyl, substituted C1-10 alkyl, substituted C1-C10 alkoxy, substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, substituted C3-C12 heteraryl having 1-3 hetervatoms selected from O, S, and N, substituted C6-12 aryl, and substituted C7-24 alkaryl, where R f is a substituted group it is substituted halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl. C7 -C24 alkaryl, C7 -C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O with substituents selected from the group consisting of halogen up to per halo, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-10 alkoxy, C6-12 aryl, C7 -C24 alkaryl, C7 -C24 aralkyl, halo substituted C1-6 alkyl up to per halo alkyl, halo substituted C6-C12 aryl up to per halo aryl, halo substituted C3-C12 cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, or c)- one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, C1-10 alkyl, C3-12 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C3-12 hetaryl having 1-3 heteroatoms selected from N, S and O, C1-alkoxy, C6-12 aryl, C7 -C24 alkaryl, C7 -C24 aralkyl, C1-6 halo substituted alkyl up to per halo alkyl, C6-C12 halo substituted aryl up to per halo aryl, C3-C12 halo substituted cycloalkyl having 0-3 heteroatoms selected from N, S and O, up to per halo cycloalkyl, halo substituted C3-C12 hetaryl up to per halo heteraryl, halo substituted C7-C24 aralkyl up to per halo aralkyl, halo substituted C7-C24 alkaryl up to per halo alkaryl, and -C(O)R g, where R g is C1-10 alkyl; -CN, -CO2R d, -OR d, -SR d, -NO2, -C(O) R c. -NR d R
c. -NR j C(O)OR e and -NR d C(O)R e, and R d and R e are independently selected from the group consisting of hydrogen, C1-10, alkyl, C1-10 alkoxy, C3-10 cycloalkyl having 0-
3 heteroatoms selected from O, N and S, C6-12 aryl, C3- C12 hetaryl with 1-3 heteroatoms selected from O, N
and S and C7 -C24 aralkyl, C7 -C24 alkaryl, up to per halo substituted C1-C10 alkyl, up to per halo substituted C3 -C10 cycloalkyl having 0-3 heteroatoms selected from O, N
and S, up to per halo substituted C6 -C14 aryl, up to per halo substituted C3 -C12 hetaryl having 1-3 heteroatoms selected from O, N, and S, halo substituted C7-C24 alkaryl up to per halo alkaryl, and up to per halo substituted C7-C24 aralkyl, W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, C1-C10 alkyl, C1-alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C7-C24 alkaryl, C7 -C24 aralkyl, C3-C12 heteroaryl having 1-3 heteroatoms selected from O, N and S, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C3-C12 hetaryl having 1-3 heteroatoms selected from O, N and S, substituted C7-C24 aralkyl, substituted C7-C24 alkaryl, substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and -Q-Ar;
R7 is independently selected from H, C1-C10 alkyl, C1-C10 alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7-C14 alkaryl, C7 -C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C1-C10 alkyl, up to per-halosubstituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per-halosubstituted C6-C14 aryl, up to per-halosubstituted C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C7-C24 aralkyl, up to per-halosubstituted C7-C24 alkaryl, and up to per-halosubstituted C4-C23 alkheteroaryl; and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, C1-C10 alkyl, alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7C24 alkaryl, C7 -C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C7-C24 alkaryl, substituted C7-C24 aralkyl and substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N
and S; wherein if Z is a substituted group, the one or more substituents are selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7.
3. A compound as in claim 1 wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a 2-, -S-{CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R7 is as defined in claim 1.
and S and C7 -C24 aralkyl, C7 -C24 alkaryl, up to per halo substituted C1-C10 alkyl, up to per halo substituted C3 -C10 cycloalkyl having 0-3 heteroatoms selected from O, N
and S, up to per halo substituted C6 -C14 aryl, up to per halo substituted C3 -C12 hetaryl having 1-3 heteroatoms selected from O, N, and S, halo substituted C7-C24 alkaryl up to per halo alkaryl, and up to per halo substituted C7-C24 aralkyl, W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, C1-C10 alkyl, C1-alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C7-C24 alkaryl, C7 -C24 aralkyl, C3-C12 heteroaryl having 1-3 heteroatoms selected from O, N and S, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C3-C12 hetaryl having 1-3 heteroatoms selected from O, N and S, substituted C7-C24 aralkyl, substituted C7-C24 alkaryl, substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, and -Q-Ar;
R7 is independently selected from H, C1-C10 alkyl, C1-C10 alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, S and N, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7-C14 alkaryl, C7 -C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C1-C10 alkyl, up to per-halosubstituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, up to per-halosubstituted C6-C14 aryl, up to per-halosubstituted C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, up to per-halosubstituted C7-C24 aralkyl, up to per-halosubstituted C7-C24 alkaryl, and up to per-halosubstituted C4-C23 alkheteroaryl; and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, C1-C10 alkyl, alkoxy, C2-C10 alkenyl, C1-C10 alkenoyl, C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, C6-C14 aryl, C3-C13 hetaryl having 1-3 heteroatoms selected from O, N and S, C7C24 alkaryl, C7 -C24 aralkyl, C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N and S, substituted C1-C10 alkyl, substituted C1-C10 alkoxy, substituted C2-C10 alkenyl, substituted C1-C10 alkenoyl, substituted C3-C10 cycloalkyl having 0-3 heteroatoms selected from O, N and S, substituted C6-C12 aryl, substituted C7-C24 alkaryl, substituted C7-C24 aralkyl and substituted C4-C23 alkheteroaryl having 1-3 heteroatoms selected from O, N
and S; wherein if Z is a substituted group, the one or more substituents are selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7.
3. A compound as in claim 1 wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a 2-, -S-{CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R7 is as defined in claim 1.
4. A compound as in claim 1 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by-OH.
5. A compound as in claim 1 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
6. A compound of claim 1 wherein B of Formula I is a substituted or unsubstituted six member aryl moiety or six member hetaryl moiety, said hetaryl moiety having 1 to 4 members selected from the group of hetaryl atoms consisting of nitrogen, oxygen and sulfur with the balance of the hetaryl moiety being carbon.
7. A compound of claim 1 wherein B of Formula I is an unsubstituted phenyl group, an unsubstituted pyridyl group, an unsubstituted pyrimidinyl, a phenyl group substituted by a substituent selected from the group consisting of halogen and Wn wherein W
and n are as defined in claim 1, a pyrimidinyl group substituted by a substituent selected from the group constituting of halogen and Wn, whereas W and n are as defined in Claim 1, or a substituted pyridyl group substituted by a substituent selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1.
and n are as defined in claim 1, a pyrimidinyl group substituted by a substituent selected from the group constituting of halogen and Wn, whereas W and n are as defined in Claim 1, or a substituted pyridyl group substituted by a substituent selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1.
8. A compound of claim 6 wherein B of Formula I is a substituted phenyl group, a substituted pyrimidinyl group, or substituted pyrridyl group substituted 1 to 3 times by 1 or more substituents selected from the group consisting of -CN, halogen, C1-C10 alkyl, C1-C10 alkoxy, -OH, up to per halo substituted C1-C10 alkyl, up to per halo substituted C1-C10 alkoxy or phenyl substituted by halogen up to per halo.
9. A compound of claim 1, wherein L, the six member cyclic structure bound directly to D, is a substituted or unsubstituted 6 member aryl moiety or a substituted or unsubstituted 6 member hetaryl moiety, wherein said hetaryl moiety has 1 to 4 members selected from the group of heteroatoms consisting of nitrogen, oxygen and sulfur with the balance of said hetaryl moiety being carbon, wherein the one or more substituents are selected from the group consisting of halogen and Wn wherein W and n are as defined in claim 1.
10. A compound of claim 8, wherein L, the 6 member cyclic structure bound directly to D, is a substituted phenyl, unsubstituted phenyl, substituted pyrimidinyl, unsubstituted pyrimidinyl, substituted pyridyl or unsubstituted pyridyl group.
11. A compound of claim 1, wherein said substituted cyclic moiety L1 comprises a to 6 membered aryl moiety or hetaryl moiety, wherein said heteraryl moiety comprises 1 to 4 members selected from the group of heteroatoms consisting of nitrogen, oxygen and sulfur.
12. A compound of claim 1, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
13. A compound of claim 3, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
14. A compound of claim 6, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
15. A compound of claim 8, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
16. A compound of claim 9, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
17. A compound of claim 10, wherein said substituted cyclic moiety L1 is phenyl, pyridinyl or pyrimidinyl.
18. A compound of claim 14, wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R7 is hydrogen or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen up to per halo.
19. A compound of claim 15, wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R7 is hydrogen or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen up to per halo.
20. A compound of claim 16, wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R74 is hydrogen or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen up to per halo.
21. A compound of claim 17, wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen and R7 is hydrogen or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen up to per halo.
22. A compound of claim 1 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
23. A compound of claim 13 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
24. A compound of claim 18 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
25. A compound of claim 19 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
26. A compound of claim 20 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
27. A compound of claim 21 wherein L1 is additionally substituted 1 to 3 times by one or more substituents selected from the group consisting of C1-C10 alkyl, up to per halo substituted C1-C10 alkyl, -CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
28. A compound of claim 1 wherein L1 is substituted by -C(O)R x.
29. A compound of claim 1 wherein L1 is substituted by -SO2R x.
30. A compound of claim 1 wherein L1 is substituted only by -C(O)R x.
31. A compound of claim 1 wherein L1 is substituted only by -SO2R x.
32. A compound of claim 1 wherein L1 is substituted by -C(O)R x or -SO2R x.
wherein R x is NR o R b.
wherein R x is NR o R b.
33. A compound of claim 13 wherein L1 is substituted by -C(O)R x or -SO2R x, wherein R x is NR a R b, and R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a or R b 15 -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen.
and O and are optionally substituted by halogen.
34. A compound of claim 18 wherein L1 is substituted by -C(O)R x or -SO2R x, wherein R x is NR a R b and R a and R b are independently hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
35. A compound of claim 19 wherein L1 is substituted by -C(O)R x, wherein R x is NR a R b and R a and R b are independently hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
36. A compound of claim 20 wherein L1 is substituted by -C(O)R x or -SO2R x, wherein R x is NR a R b and R a and R b are independently hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
37. A compound of claim 21 wherein L1 is substituted by -C(O)R x or -SO2R x, wherein R x is NR a R b and R a and R b are independently hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
38. A compound of Formula I:
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-, A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q, where L is a 6 membered aryl moiety or a 6 membered hetaryl moiety bound directly to D, L1 comprises a substituted cyclic moiety having at least 5 members, M is a bridging group having at least one atom, q is an integer of from 1-3; and each cyclic structure of L and L1 contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, and B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y)R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, R z is hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a, or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted;
the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7-, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, and X a is halogen;
Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents are selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7, with R7 as defined above; and wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-CHX a-. -CX a-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen.
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-, A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q, where L is a 6 membered aryl moiety or a 6 membered hetaryl moiety bound directly to D, L1 comprises a substituted cyclic moiety having at least 5 members, M is a bridging group having at least one atom, q is an integer of from 1-3; and each cyclic structure of L and L1 contains 0-4 members of the group consisting of nitrogen, oxygen and sulfur, and B is a substituted or unsubstituted, up to tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with at least one 6-member cyclic structure bound directly to D containing 0-4 members of the group consisting of nitrogen, oxygen and sulfur, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y)R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, R z is hydrogen or a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a, or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted;
the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7-, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, and X a is halogen;
Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents are selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7, with R7 as defined above; and wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-CHX a-. -CX a-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, X a is halogen.
39. A compound of Formula I:
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-;
A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q, where L is a substituted or unsubstituted phenyl or peritoneal moiety bound directly to D, L1 comprises a substituted phenyl, peritoneal or pyrimidinyl moiety, M is a bridging group having at least one atom, q is an integer of from 1-3; and B is a substituted or unsubstituted phenyl or pyridine group bound directly to D, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y)R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, and;
R z is hydrogen or a carbon based moiety of up to 34 carbon atoms optionally containing heteroatoms selected from N, S and O arid optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted;
the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, and X a is halogen;
Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7; and wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m,- -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-CHX a-, -CX b2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m=1-3, X a is halogen.
A-D-B (I) or a pharmaceutically acceptable salt thereof, wherein D is -NH-C(O)-NH-;
A is a substituted moiety of up to 40 carbon atoms of the formula: -L-(M-L1)q, where L is a substituted or unsubstituted phenyl or peritoneal moiety bound directly to D, L1 comprises a substituted phenyl, peritoneal or pyrimidinyl moiety, M is a bridging group having at least one atom, q is an integer of from 1-3; and B is a substituted or unsubstituted phenyl or pyridine group bound directly to D, wherein L1 is substituted by at least one substituent selected from the group consisting of -SO2R x, -C(O)R x and -C(NR y)R z, R y is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally halosubstituted, up to per halo, and;
R z is hydrogen or a carbon based moiety of up to 34 carbon atoms optionally containing heteroatoms selected from N, S and O arid optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen;
R x is R z or NR a R b where R a and R b are a) independently hydrogen, a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen, or -OSi(R f)3 where R f is hydrogen or a carbon based moiety of up to 24 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or b) R a and R b together form a 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O, or a substituted 5-7 member heterocyclic structure of 1-3 heteroatoms selected from N, S and O substituted by halogen, hydroxy or carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen; or c) one of R a or R b is -C(O)-, a C1-C5 divalent alkylene group or a substituted C1-C5 divalent alkylene group bound to the moiety L to form a cyclic structure with at least 5 members, wherein the substituents of the substituted C1-C5 divalent alkylene group are selected from the group consisting of halogen, hydroxy, and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S
and O and are optionally substituted by halogen;
where B is substituted, L is substituted or L1 is additionally substituted;
the substituents are selected from the group consisting of halogen, up to per-halo, and Wn, where n is 0-3;
wherein each W is independently selected from the group consisting of -CN, -CO2R7, -C(O)NR7R7, -C(O)-R7, -NO2, -OR7, -SR7, -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, -Q-Ar, and carbon based moieties of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by one or more substituents independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, -OR7, -SR7, -NR7R7, -NO2, -NR7C(O)R7, -NR7C(O)OR7 and halogen up to per-halo; with each R7 independently selected from H or a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, wherein Q is -O-, -S-, -N(R7)-, -(CH2)m-, -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m- CHX a-, -CX a2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m= 1-3, and X a is halogen;
Ar is a 5- or 6-member aromatic structure containing 0-2 members selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by halogen, up to per-halo, and optionally substituted by Z n1, wherein n1 is 0 to 3 and each Z is independently selected from the group consisting of -CN, -CO2R7, -C(O)R7, -C(O)NR7R7, NO2, -OR7, - SR7 -NR7R7, -NR7C(O)OR7, -NR7C(O)R7, and a carbon based moiety of up to 24 carbon atoms, optionally containing heteroatoms selected from N, S and O
and optionally substituted by one or more substituents selected from the group consisting of -CN, -CO2R7, -COR7, -C(O)NR7R7, -OR7, -SR7, -NO2, -NR7R7, -NR7C(O)R7, and -NR7C(O)OR7; and wherein M is one or more bridging groups selected from the group consisting of -O-, -S-, -N(R7)-, -(CH2)m,- -C(O)-, -CH(OH)-, -(CH2)m O-, -(CH2)m S-, -(CH2)m N(R7)-, -O(CH2)m-CHX a-, -CX b2-, -S-(CH2)m- and -N(R7)(CH2)m-, where m=1-3, X a is halogen.
40. A compound as in claim 38 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by-OH.
41. A compound as in claim 38 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
42. A compound as in claim 39 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by-OH.
43. A compound as in claim 39 wherein the cyclic structures of B and L bound directly to D are not substituted in the ortho position by a moiety having an ionizable hydrogen and a pKa of 10 or less.
44. A compound as in claim 38 wherein substituents for B and L and additional substituents for L1, are selected from the group consisting of C1-C10 alkyl up to per halo substituted C1-C10 alkyl, CN, OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
45. A compound as in claim 39 wherein substituents for B and L and additional substituents for L1, are selected from the group consisting of C1-C10 alkyl up to per halo substituted C1-C10 alkyl, CN, -OH, halogen, C1-C10 alkoxy and up to per halo substituted C1-C10 alkoxy.
46. A compound of claim 38 wherein L1 is substituted by C(O)R x or SO2R x.
47. A compound of claim 39 wherein L1 is substituted by C(O)R x or SO2R x.
48. A compound of claim 46 wherein R x is NR a R b and R a and R b are independently hydrogen and a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
49. A compound of claim 47 wherein R x is NR a R b and R a and R b are independently hydrogen and a carbon based moiety of up to 30 carbon atoms optionally containing heteroatoms selected from N, S and O and optionally substituted by halogen, hydroxy and carbon based substituents of up to 24 carbon atoms, which optionally contain heteroatoms selected from N, S and O and are optionally substituted by halogen.
50. A compound of claim 1 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid;
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline canons, alkaline earth canons, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline canons, alkaline earth canons, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
51. A compound of claim 2 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid;
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
52. A compound of claim 33 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), I-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid;
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline canons, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline canons, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
53. A compound of claim 38 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid;
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
54. A compound of claim 39 which is a pharmaceutically acceptable salt of a compound of formula I selected from the group consisting of a) basic salts of organic acids and inorganic acids selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, trifluorosulphonic acid, benzenesulfonic acid, p-toluene sulphonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, and mandelic acid; and b) acid salts of organic and inorganic bases containing cations selected from the group consisting of alkaline cations, alkaline earth cations, the ammonium cation, aliphatic substituted ammonium cations and aromatic substituted ammonium cations.
55. A compound selected from the group consisting of the 3-tert butyl phenyl ureas:
N-(3-tert-butylphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(3-tert-butylphenyl)-N'-(4-(4-acetylphenoxy)phenyl) urea;
the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(4-methoxy-3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;
the 2-methoxy-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea.
N-(3-tert-butylphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(3-tert-butylphenyl)-N'-(4-(4-acetylphenoxy)phenyl) urea;
the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(4-methoxy-3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;
the 2-methoxy-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea.
56. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 55, or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
57. A pharmaceutical composition comprising a compound of claim 2 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
58. A pharmaceutical composition comprising a compound of claim 33 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
59. A pharmaceutical composition comprising a compound of claim 38 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
60. A pharmaceutical composition comprising a compound of claim 39 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.
61. The pharmaceutical composition according to claim 56, which is for the treatment of a cancerous cell growth mediated by raf kinase.
62. The pharmaceutical composition according to claim 58, which is for the treatment of a cancerous cell growth mediated by raf kinase.
63. The pharmaceutical composition according to claim 59, which is for the treatment of a cancerous cell growth mediated by raf kinase.
64. The pharmaceutical composition according to claim 60, which is for the treatment of a cancerous cell growth mediated by raf kinase.
65. A pharmaceutical composition comprising a compound selected from the group consisting of the 3-tert butyl phenyl ureas:
N-(3-tert-butylphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(3-tert-butylphenyl)-N'-(4-(4-acetylphenoxy)phenyl) urea;
the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(4-methoxy-3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;
the 2-methoxy-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea, and a physiologically acceptable carrier, for the treatment of a cancerous cell growth mediated by raf kinase.
N-(3-tert-butylphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(3-tert-butylphenyl)-N'-(4-(4-acetylphenoxy)phenyl) urea;
the 5-tert-butyl-2-methoxyphenyl ureas:
N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1,3-dioxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(1-oxoisoindolin-5-yloxy)phenyl) urea, N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(4-methoxy-3-(N-methylcarbamoyl)phenoxy)phenyl) urea and N-(5-tert-butyl-2-methoxyphenyl)-N'-(4-(3-(N-methylcarbamoyl)phenoxy)phenyl) urea;
the 2-methoxy-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-carbamoyl-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridylthio)phenyl) urea, N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(2-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea and N-(2-methoxy-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
the 2-methoxy-4-chloro-5-(trifluoromethyl)phenyl ureas:
N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea, and N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N'-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea, and a physiologically acceptable carrier, for the treatment of a cancerous cell growth mediated by raf kinase.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11587799P | 1999-01-13 | 1999-01-13 | |
US60/115,877 | 1999-01-13 | ||
US25726699A | 1999-02-25 | 1999-02-25 | |
US09/257,266 | 1999-02-25 | ||
US42522899A | 1999-10-22 | 1999-10-22 | |
US09/425,228 | 1999-10-22 | ||
CA002359510A CA2359510C (en) | 1999-01-13 | 2000-01-12 | .omega.-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002359510A Division CA2359510C (en) | 1999-01-13 | 2000-01-12 | .omega.-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
Publications (2)
Publication Number | Publication Date |
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CA2549558A1 true CA2549558A1 (en) | 2000-07-20 |
CA2549558C CA2549558C (en) | 2010-08-31 |
Family
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CA2549558A Expired - Lifetime CA2549558C (en) | 1999-01-13 | 2000-01-12 | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
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Country | Link |
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EP (1) | EP1690853B1 (en) |
CA (1) | CA2549558C (en) |
DK (1) | DK1690853T3 (en) |
SI (2) | SI1140840T1 (en) |
UA (1) | UA73731C2 (en) |
UY (2) | UY26038A1 (en) |
Cited By (1)
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JP2005516927A (en) * | 2001-12-13 | 2005-06-09 | アボット・ラボラトリーズ | 3- (Phenyl-alkoxy) -5- (phenyl) -pyridine derivatives and related compounds as kinase inhibitors for cancer treatment |
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JP2014505052A (en) * | 2011-01-06 | 2014-02-27 | ベータ ファルマ カナダ インコーポレーテッド | New urea for cancer treatment and prevention |
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CH428747A (en) * | 1961-09-11 | 1967-01-31 | Wander Ag Dr A | Process for the production of new urea and thiourea derivatives |
CH575208A5 (en) | 1973-07-30 | 1976-05-14 | Ciba Geigy Ag | |
JPS57185219A (en) * | 1981-05-12 | 1982-11-15 | Chugai Pharmaceut Co Ltd | Remedy for cancer |
JPH0222650A (en) * | 1988-07-11 | 1990-01-25 | Konica Corp | Silver halide color photographic sensitive material |
JPH0223337A (en) * | 1988-07-12 | 1990-01-25 | Konica Corp | Silver halide photographic sensitive material containing novel coupler |
US4973675A (en) * | 1989-04-13 | 1990-11-27 | University Of Tennessee Research Center | Hybrid nitrosoureidoanthracyclines having antitumor activity |
FR2683818B1 (en) | 1991-11-14 | 1993-12-31 | Adir Cie | NOVEL 3-SULFONYLAMINO-2- (1H) -QUINOLEINONE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
WO1995033458A1 (en) * | 1994-06-02 | 1995-12-14 | Smithkline Beecham Corporation | Anti-inflammatory compounds |
US5447957A (en) * | 1994-06-02 | 1995-09-05 | Smithkline Beecham Corp. | Anti-inflammatory compounds |
DE69622183D1 (en) * | 1995-11-07 | 2002-08-08 | Kirin Brewery | CHINOLINE DERIVATIVES AND CHINAZOLE DERIVATIVES, WHICH INHIBIT THE AUTOPHOSPHORYLATION OF THE GROWTH FACTOR RECEPTOR DERIVING FROM BLOOD PLATPLES AND THEIR PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
RU2146254C1 (en) | 1996-06-29 | 2000-03-10 | Самдзин Фармасьютикал Ко., Лтд. | Derivatives of piperazine and method of their synthesis |
PT1019040E (en) * | 1997-05-23 | 2005-01-31 | Bayer Pharmaceuticals Corp | INHIBITION OF THE ACTIVITY OF P38-KINASE BY MEANS OF ARILUREIAS |
EP0986382B1 (en) * | 1997-05-23 | 2008-06-25 | Bayer Pharmaceuticals Corporation | Raf kinase inhibitors |
WO1999020617A1 (en) * | 1997-10-21 | 1999-04-29 | Active Biotech Ab | Antiinflammatory thiadiazolyl ureas which act as lfa-1 and mac-1 inhibitors |
WO1999032110A1 (en) * | 1997-12-22 | 1999-07-01 | Bayer Corporation | INHIBITION OF p38 KINASE ACTIVITY USING ARYL AND HETEROARYL SUBSTITUTED HETEROCYCLIC UREAS |
ATE529109T1 (en) * | 1997-12-22 | 2011-11-15 | Bayer Healthcare Llc | INHIBITION OF P38 KINASE ACTIVITY BY SUBSTITUTED HETEROCYCLIC UREAS |
CZ301102B6 (en) * | 1997-12-22 | 2009-11-04 | Bayer Corporation | Substituted aryl ureas, pharmaceutical compositions containing them and their use |
JP3887769B2 (en) * | 1997-12-22 | 2007-02-28 | バイエル コーポレイション | Inhibition of p38 kinase using symmetric and asymmetric diphenylureas |
AU2725000A (en) * | 1999-01-13 | 2000-08-01 | Bayer Corporation | Omega-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors |
-
2000
- 2000-01-12 EP EP05028442A patent/EP1690853B1/en not_active Expired - Lifetime
- 2000-01-12 DK DK05028442.1T patent/DK1690853T3/en active
- 2000-01-12 SI SI200030837T patent/SI1140840T1/en unknown
- 2000-01-12 SI SI200031058T patent/SI1690853T1/en unknown
- 2000-01-12 CA CA2549558A patent/CA2549558C/en not_active Expired - Lifetime
- 2000-02-25 UY UY26038A patent/UY26038A1/en not_active IP Right Cessation
- 2000-12-01 UA UA2001075426A patent/UA73731C2/en unknown
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2009
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Cited By (1)
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JP2005516927A (en) * | 2001-12-13 | 2005-06-09 | アボット・ラボラトリーズ | 3- (Phenyl-alkoxy) -5- (phenyl) -pyridine derivatives and related compounds as kinase inhibitors for cancer treatment |
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UY26038A1 (en) | 2000-09-29 |
SI1690853T1 (en) | 2010-07-30 |
EP1690853B1 (en) | 2010-03-10 |
EP1690853A1 (en) | 2006-08-16 |
SI1140840T1 (en) | 2006-06-30 |
UA73731C2 (en) | 2005-09-15 |
DK1690853T3 (en) | 2010-06-07 |
CA2549558C (en) | 2010-08-31 |
UY32230A (en) | 2010-06-30 |
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