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US 2003/0144278 A1Published application
Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
AssigneeBayer Aktiengesellschaft
InventorsBernd Riedl, Jacques Dumas, Uday Khire, Timothy B. Lowinger, William J. Scott, Roger A. Smith, Jill E. Wood, Mary-Katherine Monahan, Reina Natero, Joel Renick, Robert N. Sibley
Life of this patent
Estimating the term…
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.
Claims67
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 stricture 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 —SO2Rx, —C(O)Rx and —C(NRy)Rz,
- Ry 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,
- Rz 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;
- Rx is Rz or NRaRb where Ra and Rb 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(Rf)3 where Rf 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) Ra and Rb together form a 5-7 member heterocyclic stricture 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 Ra or Rb 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)mO—, —(CH2)mS—, —(CH2)mN(R7)—, —O(CH2)m—CHXa, —CXa2—, —S—(CH2)m— and —N(R7)(CH2)m—, where m=1-3, and Xa 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 Zn1, 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.
21 more elements
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 —SO2Rx, —C(O)Rx and —C(NRy)Rz,
- Ry 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,
- Rz 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;
- Rx is Rz or NRaRb where Ra and Rb 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(Rf)3 where Rf 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) Ra and Rb 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 Ra or Rb 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)mO—, —(CH2)mS—, —(CH2)mN(R7)—, —O(CH2)m—CHXa—, —CXa2—, —S—(CH2)m— and —N(R7)(CH2)m—, where m=1-3, and Xa 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 Zn1, 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)mO—, —(CH2)mS—, —(CH2)mN(R7)—, —O(CH2)m—CHXa—, —CHa2—, —S—(CH2)m— and —N(R7)(CH2)m—, where m=1-3, Xa is halogen.
22 more elements
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 —SO2Rx, —C(O)Rx and —C(NRy)Rz,
- Ry 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;
- Rz 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;
- p2 Rx is Rz or NRaRb where Ra and Rb 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(Rf)3 where Rf 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) Ra and Rb 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 Ra or Rb 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)mO—, —(CH2)mS—, —(CH2)mN(R7)—, —O(CH2)m—CHXa—, —CXa213 , —S—(CH2)m— and —N(R7)(CH2)m—, where m=1-3, and Xa 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 Zn1, 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)mO—, —(CH2)mS—, —(CH2)mN(R7)—, —O(CH2)m—CHXa, 13 CXa2—, —S—(CH2)m— and —N(R7)(CH2)m—, where m=1-3, Xa is halogen.
22 more elements
A compound selected from the group consisting of
- 3-tert butyl phenyl ureas of Table 1 above;
- 5-tert butyl-2-methoxyphenyl ureas of Table 2 above;
- 5-(trifluoromethyl)-2 phenyl ureas of Table 3 above;
- 3-(trifluoromethyl)-4 chlorophenyl ureas of Table 4 above;
- 3-(trifluoromethyl)-4-bromophenyl ureas of Table 5 above;
- 5-(trifluoromethyl)-4-chloro-2 methoxyphenyl ureas of Table 6 above;
- and ureas 101-103 in Table 7 above.
4 more elements
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 4-chloro-3-(trifluoromethyl)phenyl ureas:
- 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 and
- N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea.
- the 4-romo-3-(trifluoromethyl)phenyl ureas:
- 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 and
- N-(4-bromo-3-(trifluoromethyl)phenyl)-N′-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
- and
- 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,
- N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
- N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N′-(2-chloro-4-(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.
30 more elements
A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administrating a compound selected from the group consisting of
- 3-tert butyl phenyl ureas of Table 1 above;
- 5-tert butyl-2-methoxyphenyl ureas of Table 2 above;
- 5-(trifluoromethyl)-2 phenyl ureas of Table 3 above;
- 3-(trifluoromethyl)-4 chlorophenyl ureas of Table 4 above;
- 3-(trifluoromethyl)-4-bromophenyl ureas of Table 5 above;
- 5-(trifluoromethyl)-4-chloro-2 methoxyphenyl ureas of Table 6 above;
- and
- ureas 101-103 in Table 7 above.
5 more elements
A method for the treatment of a cancerous cell growth mediated by raf kinase, comprising administrating 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 4-chloro-3-(trifluoromethyl)phenyl ureas:
- 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 and
- N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea;
- the 4-romo-3-(trifluoromethyl)phenyl ureas:
- 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 and
- N-(4-bromo-3-(trifluoromethyl)phenyl)-N′-(3-chloro-4-(2-(N-methylcarbamoyl)(4-pyridyloxy))phenyl) urea;
- and
- 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,
- N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea,
- N-(2-methoxy-4-chloro-5-(trifluoromethyl)phenyl)-N′-(2-chloro-4-(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.
30 more elements
Dependencies are inferred from the claim text.