Claims
- 1. A 1,4-disubstituted benzo-fused compound of the formula (I):
- 2. The compound according to claim 1 wherein:
ring A and the phenyl ring to which it is fused form: 283
- 3. The compound according to claim 2 wherein:
n is 0; ring A and the phenyl ring to which it is fused form: 284G is
phenyl, pyridinyl, pyridonyl, piperidinyl, tetrahydropyranyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, benzimidazolyl, benzoxazolyl, benzooxazolonyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, indanyl, indenyl, indolyl, indolinyl, indolonyl, 2,3-dihydro-1H-indolyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one or more R1 or R2; L is:
—O—, >C(O), >C(S), —OCH2—, —CH2—, —CH2CH2—, —CH2CH2CH2—, —C(CH3)2—, —CH(OH)—, —CH2CH(OH)—, —CH(OH)CH2—, —OCH2CH2—, —OCH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2, —OCH2C(O)—, —CH═CH—CH2— or —CH═CHCH2CH2, —NH—, —NHCH2—, —NHCH2CH2—, S(O)m—, —S(O)mCH2—, —S(O)mCH2CH2— and —S(O)mCH2CH2CH2—; Q is:
pyrimidinyl or morpholinyl each mono- or disubstituted by C1-3 alkyl or phenyl, or Q is phenyl, pyridinyl, pyridazinyl, imidazolyl, thiazolyl, oxazolyl, pyrazinyl, pyrazolyl, tetrahydropyranyl, piperazinyl, piperidinyl, triazolyl, 2-oxo-2H-pyran-4-yl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1]heptanyl, 1-oxo-λ4-thiomorpholinyl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene; R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with one to three C3-6 cycloalkyl, hydroxy or phenyl; N-morpholinyl; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3 alkyl or phenyl; R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated or C1-4 branched or unbranched alkoxy optionally partially or fully halogenated R3 is(J)0-1—L′—S(O)m—NH— or (J)0-1—L′—O—C(O)—NH—, wherein for R3:
L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl; J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, phenyl, naphthyl, morpholinyl, piperidinyl, piperazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl and isothiazolyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl; each of the above J is optionally substituted by one to two R4; R4 is oxo or mono- or di-C1-3 alkylamino; Y is not present; m is 2; and X is O.
- 4. The compound according to claim 3 wherein:
G is
phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indolyl, indolinyl, indolonyl, indolinonyl, piperidinyl or tetrahydropyranyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl.
- 5. The compound according to claim 4 wherein:
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, dihydrobenzofuranyl, indanyl, indolinyl, indolonyl or indolinonyl wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L is:
—O—, >C(O), —C(CH3)2—, —O—CH2—, —CH2—, —OCH2CH2—, —OCH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2—, —NH—, —NHCH2—, —NHCH2CH2—, —S(O)m—, —S(O)mCH2—, —S(O)mCH2CH2—, —S(O)mCH2CH2CH2—, —CH2CH2—, —CH2CH2CH2— or —OCH2C(O)—; each R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated and optionally substitute d with phenyl or R1 is N-morpholinyl; cyclopropyl, cyclopentanyl, cyclohexanyl or bicyclopentanyl optionally substituted with one to three methyl groups optionally be partially or fully halogenated, cyano, hydroxymethyl or phenyl; Q is
morpholinyl or pyrimidinyl each mono- or di-substituted by C1-3 alkyl or phenyl, or Q is phenyl, imidazolyl, tetrahydropyranyl, pyridinyl, 2-oxo-2H-pyran-4-yl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1 ]heptanyl, 1-oxo-λ4-thiomorpholinyl, triazolyl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene.
- 6. The compound according to claim 5 wherein:
G is phenyl substituted by one R3 and further independently substituted by one to two R1 or R2; and L is:
—O—, >C(O) or —C(CH3)2—; Q is morpholinyl or pyrimidinyl each mono- or di-substituted by C1-3 alkyl or phenyl, or Q is pyridinyl, 2-oxo-2H-pyran-4-yl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1]heptanyl, 1-oxo-λ4-thiomorpholinyl, triazolyl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene; R3 isL′—S(O)2—NH or (J)0-1—L′—O—C(O)—NHwherein L′ is C1-5alkyl.
- 7. The compound according to claim 6 wherein:
R1 is
tert-butyl optionally partially or fully halogenated; R2 is independently:
C1-3 alkyl or C1-3 alkoxy; Q is N-morpholinyl or pyrimidin-4-yl each mono- or di-substituted by methyl or phenyl, or Q is pyridin-4-yl, 2-oxo-2H-pyran-4-yl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1]heptanyl, 1-oxo-λ4-thiomorpholine-4-yl, triazol-2-yl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene.
- 8. The compound according to claim 7 wherein
L is —O—, >C(O) or —C(CH3)2—; and R3 is C1-3 alkyl-S(O)2—N—H— or C1-3 alkyl-O—C(O)—NH—.
- 9. The compound according to claim 8 wherein R3 is CH3—S(O)2—N—H— or CH3—O—C(O)—NH—.
- 10. The compound according to claim 2 wherein:
n is 1; ring A and the phenyl ring to which it is fused form: 285G is
phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, piperidinyl, tetrahydropyranyl, benzimidazolyl, benzoxazolyl, benzooxazolonyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, indanyl, indenyl, indolyl, indolinyl, indolonyl, 2,3-dihydro-1H-indolyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one or more R1 or R2; L is:
—O—, —OCH2—, —CH2—, —CH(OH)—, —CH2—CH(OH)—, —CH(OH)CH2—, —OCH2CH2—, —CH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2—, —CH2CH2—, —CH2CH2CH2—, —OCH2C(O)—, —CH═CHCH2— or —CH═CHCH2CH2—, —NH—, —NHCH2—, —NHCH2CH2—, —S(O)m—, —S(O)mCH2—, —S(O)mCH2CH2— and —S(O)mCH2CH2CH2—; Q is:
phenyl, pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, tetrahydropyranyl, thiazolyl, oxazolyl, pyrazinyl, pyrazolyl, morpholinyl, thiomorpholinyl, piperazinyl or piperidinyl; R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-6 cycloalkyl, hydroxy and phenyl; N-morpholinyl; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3 alkyl or phenyl; R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated or C1-4 branched or unbranched alkoxy optionally partially or fully halogenated; R3 is(J)0-1—L′—S(O)m—N—H— or (J)0-1—L′—O—C(O)—NH—, wherein for R3:
L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl; J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, phenyl, naphthyl, morpholinyl, piperidinyl, piperazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl and isothiazolyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl; each of the above J is optionally substituted by one to two R4; R4 is oxo or mono- or di-C1-3 alkylamino; Y is
a bond, —O—, >C(O), —NH—, —C(O)—NH—, —S—, C1-5 alkyl branched or unbranched, C2-5 alkenyl, C1-3 acyl, C1-3 alkyl(OH), heterocycle selected from morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl and tetrahydrofuranyl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl and isothiazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is further covalently attached to NR5R6, C1-3 alkyl, C3-6 cycloalkylC0-2alkyl, hydroxy, C1-3 alkoxy, phenoxy, phenylC0-4 alkyl, piperazinylC0-4 alkyl, piperidinyl C0-4alkyl, pyrrolidinylC0-4 alkyl, morpholinylC0-4 alkyl, tetrahydrofuranylC0-4 alkyl or pyridinyl C0-4alkyl, each abovelisted heterocycle, heteroaryl and phenyl is optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6—C(O)— or C1-4 acyl, each R5 and R6 are independently hydrogen, phenylC0-3alkyl optionally substituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, or R5 and R6 are C1-2 acyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-4 alkoxy, hydroxy or mono or diC1-3 alkyl amino; m is 2; and X is O.
- 11. The compound according to claim 10 wherein:
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indolyl, indolinyl, indolonyl, indolinonyl, piperidinyl or tetrahydropyranyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl.
- 12. The compound according to claim 11 wherein:
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, dihydrobenzofuranyl, indanyl, indolinyl, indolonyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L is:
—O—, —OCH2—, —CH2—, —CH2CH2—, —CH2CH2CH2—, —OCH2CH2—, —OCH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2—, —NH—, —NHCH2—, —NHCH2CH2—, —S(O)m—, —S(O)mCH2—, —S(O)mCH2CH2—, —S(O)mCH2CH2CH2— or —OCH2C(O)—; each R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with phenyl; N-morpholinyl; cyclopropyl, cyclopentanyl, cyclohexanyl or bicyclopentanyl optionally substituted with one to three methyl groups optionally partially or fully halogenated, cyano, hydroxymethyl or phenyl; Q is
phenyl, pyridinyl, pyrimidinyl, imidazolyl, tetrahydropyranyl or morpholinyl; Y is
a bond, —O—, —S—, >C(O), —NH—, —C(O)—NH—, —CH(C1-2 alkyl)—; or Y is C1-2 alkyl, C1-2 alkyl(OH), C2-4 alkenyl, C1-2 acyl, imidazolyl, pyrazolyl, pyrrolidinyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl or phenyl each optionally substituted by one to two hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is further covalently attached to NR5R6, C1-3 alkyl, C3-6 cycloalkylC0-2alkyl, hydroxy, C1-3 alkoxy, phenoxy, phenylC0-4 alkyl, piperazinylC0-4 alkyl, piperidinylC0-4 alkyl, pyrrolidinylC0-4 alkyl, morpholinylC0-4 alkyl, tetrahydrofuranylC0-4 alkyl or pyridinylC0-4 alkyl each abovelisted heterocycle, heteroaryl or phenyl is optionally substituted by one to two C1-5 alkoxycarbonyl, NR5R6—C(O)—, C1-4 alkyl, C1-4 acyl or hydroxy; each R5 and R6 are independently hydrogen, phenylC0-3 alkyl optionally substituted by halogen or C1-3 alkyl, acetyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-3 alkoxy, hydroxy, mono or diC1-3 alkyl amino.
- 13. The compound according to claim 12 wherein:
G is phenyl substituted by one R3 and further independently substituted by one to two R1 or R2; and L is:
—O—, —NH—, —CH2— or —S(O)m—; Q is pyridinyl or phenyl; R3 is(J)0-1—L′—S(O)2—NH or (J)0-1—L′—O—C(O)—NHwherein L′ is C1-5alkyl; wherein J is cyclobutenyl, N-morpholinyl, N-piperidinyl, N-piperazinyl or N-pyrrolidinyl, each J is optionally substituted by one to two R4.
- 14. The compound according to claim 13 wherein:
L is:
—O— or —CH2—; R1 is
tert-butyl optionally partially or fully halogenated; R2 is independently:
C1-3 alkyl or C1-3 alkoxy; Q is pyridinyl attached to L at the pyridin-4yl position or phenyl which has Y attached at the meta position; Y is
a bond, —O—, —S—, >C(O), —CH(CH3)—, —CH(OH)—, —NH—, —C(O)—NH—; or Y is —CH2—, —CH═CHCH2—, imidazolyl, thiazolyl, pyrrolidinyl, oxazolyl or phenyl each optionally substituted by one hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is further covalently attached to NR5R6, C1-3 alkyl, C3-6 cycloalkylC0-2alkyl, C1-3 alkoxy, phenoxy, hydroxy, phenylC0-4 alkyl, piperazinylC0-4 alkyl, piperidinylC0-4 alkyl, pyrrolidinylC0-4 alkyl, morpholinylC0-4 alkyl, tetrahydrofuranylC0-4 alkyl or pyridinylC0-4 alkyl, each abovelisted heterocycle, heteroaryl or phenyl is optionally substituted by one to two C1-5 alkoxycarbonyl, NR5R6—C(O)—, C1-3 alkyl, C1-3 acyl, halogen or hydroxy; each R5 and R6 are independently hydrogen, phenylC0-3 alkyl optionally substituted by halogen or C1-3 alkyl, acetyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-2 alkoxy, hydroxy or mono or diC1-3 alkyl amino.
- 15. The compound according to claim 14 wherein:
L is —O—; Y is
a bond, —O—, —S—, —S(O)—, —S(O)2—, —CH2—, —CH(OH)—, —CH(CH3)—, —NH—, —C(O)—NH—, >C(O), ═CH═CHCH2—; or Y is imidazolyl, thiazolyl, pyrrolidinyl, oxazolyl or phenyl each optionally substituted by one hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is further covalently attached to NR5R6, methyl, ethyl, methoxy, phenoxy, hydroxy, C3-6 cycloalkylC0-2alkyl, phenylC0-1 alkyl, piperazinylC0-2 alkyl, piperidinyl, pyrrolidinylC0-1 alkyl, morpholinylC0-2 alkyl tetrahydrofuranylC0-2 alkyl or pyridinyl, each abovelisted heterocycle, heteroaryl or phenyl is optionally substituted by one to two C3-5 alkoxycarbonyl, acetyl, N-methylamide, N-ethylamide, methyl, ethyl, halogen or hydroxy; each R5 and R6 are independently hydrogen, phenyl, benzyl each optionally substituted by chlorine, bromine, fluorine or C1-2 alkyl, acetyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by methoxy, hydroxy or mono or diC1-3 alkyl amino; and R3 is C1-3 alkyl-S(O)2—N—H— or C1-3 alkyl—O—C(O)—NH—.
- 16. The compound according to claim 15 wherein R3 is CH3—S(O)2—N—H— or CH3—O—C(O)—NH—.
- 17. The compound according to claim 2 wherein:
n is 2; ring A and the phenyl ring to which it is fused form: 286G is
phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, piperidinyl, tetrahydropyranyl, benzimidazolyl, benzoxazolyl, benzooxazolonyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, indanyl, indenyl, indolyl, indolinyl, indolonyl, 2,3-dihydro-1H-indolyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one or more R1 or R2; L is:
—O—, >C(O), —OCH2—, —CH2—, —CH(OH)—, —CH2—CH(OH)—, —CH(OH)CH2—, —OCH2CH2—, —OCH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2—, —CH2CH2—, —CH2—OCH2C(O)—, —CH═CHCH2— or —CH═CHCH2CH2—, —NH—, —NHCH2—, —NHCH2CH2—, —S(O)m—, —S(O)mCH2—, —S(O)mCH2CH2— and —S(O)mCH2CH2CH2—; Q is:
phenyl, pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, thiazolyl, oxazolyl, pyrazinyl, pyrazolyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, piperazinyl or piperidinyl each optionally substituted by one C1-6 alkyl or phenyl; R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-6 cycloalkyl, hydroxy and phenyl; N-morpholinyl; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3 alkyl or phenyl; R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated or C1-4 branched or unbranched alkoxy optionally partially or fully halogenated; R3is(J)0-1—L′—S(O)m—NH— or (J)0-1—L′—O—C(O)—NH—, wherein for R3:
L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl; J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, phenyl, naphthyl, morpholinyl, piperidinyl, piperazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl and isothiazolyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl; each of the above J is optionally substituted by one to two R4; R4 is oxo or mono- or di-C1-3 alkylamino; Y is
a bond, —O—, >C(O), —NH—, —C(O)—NH—, —S—, C1-5 alkyl branched or unbranched, C2-5 alkenyl, C1-3 acyl, C1-3 alkyl(OH), heterocycle selected from morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl or tetrahydrofuryl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl, indolyl or isothiazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is optionally further covalently attached to phenylC0-4 alkyl, each R5 and R6 are independently hydrogen, phenylC0 3alkyl optionally substituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, C1-2 acyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-4 alkoxy, hydroxy or mono or diC1-3 alkyl amino; m is 2; and X is O.
- 18. The compound according to claim 17 wherein:
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indolyl, indolinyl, indolonyl, indolinonyl, piperidinyl or tetrahydropyranyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl or amidoC1-5 alkyl.
- 19. The compound according to claim 18 wherein
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, dihydrobenzofuranyl, indanyl, indolinyl, indolonyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L is:
—O—, >C(O), —OCH2—, —CH2—, —OCH2CH2—, —OCH2CH2CH2—, —OCH2CH2(CH3)—, —OCH2(CH3)CH2—, —NH—, —NHCH2—, —NHCH2CH2—, —S(O)m—, S(O)mCH2—, —S(O)mCH2CH2—, —S(O)mCH2CH2CH2—, —CH2CH2—, —CH2CH2CH2— or —OCH2C(O)—; each R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with phenyl or R1 is N-morpholinyl; cyclopropyl, cyclopentanyl, cyclohexanyl or bicyclopentanyl optionally substituted with one to three methyl groups optionally be partially or fully halogenated, cyano, hydroxymethyl or phenyl; substituted by methyl; Q is
phenyl, pyridinyl, pyrimidinyl, imidazolyl, tetrahydropyranyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl or morpholinyl each optionally substituted by one C1-3 alkyl or phenyl; Y is
a bond, —O—, —S—, >C(O), —NH—, —C(O)—NH—, —CH(C1-2 alkyl)—; or Y is C1-2 alkyl, C1-2 alkyl(OH), C2-4 alkenyl, C1-2 acyl, imidazolyl, pyrazolyl, thienyl, pyrrolidinyl, pyrrolyl, indolyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl or phenyl each optionally substituted by one to two hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is optionally further covalently attached to phenylC0-4 alkyl; each R5 and R6 are independently hydrogen, phenylC0-3 alkyl optionally substituted by halogen or C1-3 alkyl, acetyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-3 alkoxy, hydroxy, mono or diC1-3 alkyl amino.
- 20. The compound according to claim 19 wherein:
G is phenyl substituted by one R3 and further independently substituted by one to two R1 or R2; and L is:
>C(O), —O—, —NH—, —CH2— or —S(O)m—; Q is pyridinyl, morpholinyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl or phenyl each optionally substituted by methyl or phenyl; R3 isL′—S(O)2—NH or L′—O—C(O)—NH—wherein L′ is C1-5alkyl.
- 21. The compound according to claim 20 wherein:
L is:
>C(O), —O— or —CH2—; R1 is
tert-butyl optionally partially or fully halogenated; R2 is independently:
C1-3 alkyl or C1-3 alkoxy; Q is N-morpholinyl optionally substituted at the 6-position by methyl or phenyl or Q is 8-oxa-3-aza-bicyclo[3.2.1]octanyl; Y is
—O—, >C(O), —CH(CH3)—, —CH(OH)—, —C(O)—NH—; or Y is CH2—, CH2CH2OH, pyrrolidinyl, pyrrolyl, indolyl or phenyl each optionally substituted by one hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—; wherein each Y is optionally further covalently attached to phenyl; each R5 and R6 are independently hydrogen, phenylC0-3 alkyl optionally subtituted by halogen or C1-3 alkyl, acetyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-2 alkoxy, hydroxy or mono or diC1-3 alkyl amino.
- 22. The compound according to claim 21 wherein:
L is >C(O); Y is
—O—, —CH2—, —CH2CH2OH; or Y is pyrrolyl, indolyl or phenyl each optionally substituted by one C1-5 alkoxycarbonyl; and R3 is C1-3 alkyl-S(O)2—NH— or C1-3 alkyl-O—C(O)—NH—.
- 23. The compound according to claim 22 wherein R3 is CH3—S(O)2—NH— or CH3—O—C(O)—NH—.
- 24. The compound according to claim 2 wherein:
n is 0 or 1; ring A and the phenyl ring to which it is fused form: 287L is
>CRxRy wherein
Rx and Ry are each independently hydrogen, heterocycleC0-4 alkyl wherein the heterocyclic moiety is chosen from piperidinyl, morpholinyl and piperazinyl, imidazolylC0-4 alkyl or phenylC0-4 alkyl; G is
phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, piperidinyl, tetrahydropyranyl, benzimidazolyl, benzoxazolyl, benzooxazolonyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, indanyl, indenyl, indolyl, indolinyl, indolonyl, 2,3-dihydro-1H-indolyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one or more R1 or R2; Q is:
phenyl, pyrimidinyl, imidazolyl, pyridinyl, tetrahydropyranyl or morpholinyl; R1 is independently: C3-5 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-6 cycloalkyl, hydroxy and phenyl;
N-morpholinyl; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3 alkyl or phenyl; R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated or C1-4 branched or unbranched alkoxy optionally partially or fully halogenated; R3 is(J)0-1—L′—S(O)m—NH— or (J)0-1—L′—O—C(O)—NH—, wherein for R3:
L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl, amidoC1-5 alkyl; J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, phenyl, naphthyl, morpholinyl, piperidinyl, piperazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl and isothiazolyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl; each of the above J is optionally substituted by one to two R4; R4 is oxo or mono- or di-C1-3 alkylamino; Y is
a bond or >C(O), further covalently attached to NR5R6, C1-3 alkyl, C3-6 cycloalkylC0-2alkyl, hydroxy, C1-3 alkoxy, phenoxy, phenylC0-4 alkyl, piperazinylC0-4 alkyl, piperidinyl C0-4alkyl, pyrrolidinylC0-4 alkyl, morpholinylC0-4 alkyl, tetrahydrofuranylC0-4 alkyl or pyridinyl C0-4alkyl, each abovelisted heterocycle, heteroaryl and phenyl are optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6—C(O)— or C1-4 acyl, each R5 and R6 are independently hydrogen, phenylC0-3alkyl optionally subtituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, C1-2 acyl, benzoyl or C1-4 branched or unbranched alkyl optionally substituted by C1-4 alkoxy, hydroxy or mono or diC1-3 alkyl amino; m is 2; and X is O.
- 25. The compound according to claim 24G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, pyrazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indolyl, indolinyl, indolonyl, indolinonyl, piperidinyl or tetrahydropyranyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; and L′ is
a bond, C1-5 alkyl, hydroxy C1-5 alkyl, C2-4 alkenyl or amidoC1-5 alkyl.
- 26. The compound according to claim 25 wherein:
G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl, isoquinolinyl, dihydrobenzofuranyl, indanyl, indolinyl, indolonyl or indolinonyl, wherein G is substituted by one R3 and further substituted by one to three R1 or R2; L is:
>CRxRy wherein
one of Rx and Ry is hydrogen and the other is heterocycle wherein the heterocyclic moiety is chosen from piperidinyl, morpholinyl and piperazinyl, imidazolyl or benzyl; each R1 is independently:
C3-5 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with phenyl or R1 is N-morpholinyl; cyclopropyl, cyclopentanyl, cyclohexanyl or bicyclopentanyl optionally substituted with one to three methyl groups optionally be partially or fully halogenated, cyano, hydroxymethyl or phenyl; cyclopentyloxy or cyclohexyloxy which are optionally partially or fully halogenated; 2-tetrahydrofuranyl substituted by methyl; Q is
phenyl, pyridinyl, pyrimidinyl, imidazolyl, tetrahydropyranyl or morpholinyl; Y is
a bond or >C(O), further covently attached to NR5R6, piperazinylC1-2 alkyl, piperidinylC1-2 alkyl, pyrrolidinylC1-2 alkyl, morpholinylC1-2 alkyl, tetrahydrofuranylC1-2 alkyl or pyridinylC1-2 alkyl; each R5 and R6 are independently hydrogen or C1-4 branched or unbranched alkyl optionally substituted by C1-3 alkoxy, hydroxy, mono or diC1-3 alkyl amino.
- 27. The compound according to claim 26 wherein:
G is phenyl substituted by one R3 and further independently substituted by one to two R1 or R2; and L is:
>CRxRy wherein
one of Rx and Ry is hydrogen and the other is heterocycle wherein the heterocyclic moiety is chosen from piperidinyl, morpholinyl and piperazinyl, imidazolyl or benzyl; Q is phenyl, pyridinyl, tetrahydropyranyl or morpholinyl; R3 is(J)0-1—L′—S(O)2—NH or (J)0-1—L′—O—C(O)—NHwherein L′ is C1-5alkyl; J is cyclobutenyl, N-morpholinyl, N-piperidinyl, N-piperazinyl or N-pyrrolidinyl, each J is optionally substituted by one to two R4.
- 28. The compound according to claim 27 wherein:
R1 is
tert-butyl optionally partially or fully halogenated; R2 is independently:
C1-3 alkyl or C1-3 alkoxy; Q is pyridin-4-yl, tetrahydropyran-4-yl or N-morpholinyl; Y is
a bond or >C(O), further covently attached to NR5R6 or pyrrolidinylC1-2 alkyl; each R5 and R6 are independently hydrogen or C1-4 branched or unbranched alkyl.
- 29. The compound according to claim 28 wherein R3 is C1-3 alkyl-S(O)2—NH— or C1-3 alkyl-O—C(O)—NH—.
- 30. The compound according to claim 29 wherein R3 is CH3—S(O)2—NH— or CH3—O—C(O)—NH—.
- 31. A compound selected from the group consisting of:
N-(5-tert-Butyl-3-{3-[4-(2-isopropyl-6-methyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2,6-dimethyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxo-2H-pyran-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxo-2H-pyran-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(cis-2,6-dimethyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(trans-2,6-dimethyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; N-(5-tert-Butyl-3-{3-[4-(trans-2,6-dimethyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(cis-2,6-dimethyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxa-5-aza-bicyclo[2.2.1]heptane-5-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxa-5-aza-bicyclo[2.2.1]heptane-5-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-thia-5-aza-bicyclo[2.2.1]heptane-5-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-thia-5-aza-bicyclo[2.2.1]heptane-5-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(1-oxo-λ4-thiomorpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(1-oxo-λ4-thiomorpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2(7),3,5-triene-11-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca -2(7),3,5-triene-11-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(3-methyl-2-phenyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(3-methyl-2-phenyl-morpholine-4-carbonyl)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(1-methyl-1-pyridin-4-yl-ethyl)naphthalen-1-yl]ureido}phenyl)methanesulfonamide N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-methoxy-6-methyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-isopropoxy-6-methyl-pyrimidin-4-yloxy)-naphthalen -1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-([1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-([1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{c3-[4-(4-isopropoxy-6-methoxy-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureidol -2-methoxy-phenyl)-methanesulfonamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen -1-yloxy}-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester; N-[3-(3-{4-[2-(4-Acetyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide; N-[3-(3-{4-[2-(4-Acetyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid ethylamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-piperazine-1-carboxylic acid ethylamide; N-[5-tert-Butyl-3-(3-{4-[2-(4-ethyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(4-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(2,6-dimethyl-morpholin-4-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(2,6-dimethyl-morpholine-4-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3-ethyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3-ethyl-4-methyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3-ethyl-4-methyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[3-(3-{4-[2-(4-Acetyl-3-ethyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide; N-[3-(3-{4-[2-(4-Acetyl-3-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-ylmethyl)-2-ethyl-piperazine-1-carboxylic acid ethylamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-2-ethyl-piperazine-1-carboxylic acid ethylamide; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-ylmethyl)-2-ethyl-piperazine-1-carboxylic acid tert-butyl ester; 4-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-2-ethyl-piperazine-1-carboxylic acid tert-butyl ester; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(4-hydroxy-piperidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3R-hydroxy-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3S-hydroxy-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-pyrrolidin-1-ylmethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-piperidin-1-ylmethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(piperidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-diethylaminomethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; 4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carboxylic acid diethylamide; N-(5-tert-Butyl-3-{3-[4-(2-dimethylaminomethyl-pyridin4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; 4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carboxylic acid dimethylamide; N-[5-tert-Butyl-3-(3-{4-[2-(3S-dimethylamino-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3S-dimethylamino-pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3R-dimethylamino-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3R-dimethylamino-pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxazol-5-yl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-oxazol-5-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-methyl-3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[3-(3-{4-[2-(3-Benzyl-3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[3-(2-morpholin-4-yl-ethyl)-3H-imidazol-4-yl]-pyridin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-phenyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; 2-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-yl)-thiazole-4-carboxylic acid ethyl ester; 2-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-yl)-thiazole-4-carboxylic acid methylamide; 2-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-yl)-thiazole-4-carboxylic acid dimethylamide; 2-(4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-yl)-thiazole-4-carboxylic acid (2-diethylamino-ethyl)-amide; N-[5-tert-Butyl-3-(3-{4-[2-(4-dimethylaminomethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-morpholin-4-ylmethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; [5-tert-Butyl-3-(3-{4-[2-(3S-dimethylamino-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3S-dimethylamino-pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3R-dimethylamino-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3R-dimethylamino-pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(2-dimethylaminomethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(2-dimethylcarbamoyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(2-diethylaminomethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(2-diethylcarbamoyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; N-[5-tert-Butyl-3-(3-{4-[2-(1-dimethylamino-ethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; [5-tert-Butyl-3-(3-{4-[2-(1-dimethylamino-ethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-pyrrolidin-1-ylmethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(pyrrolidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-piperidin-1-ylmethyl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(piperidine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3R-hydroxy-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3S-hydroxy-pyrrolidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-hydroxy-piperidin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [3-(3-{4-[2-(4-Acetyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-carbamic acid methyl ester; [3-(3-{4-[2-(4-Acetyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-ethylcarbamoyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-ethylcarbamoyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; 4-(4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-ethyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(2,6-dimethyl-morpholin-4-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(2,6-dimethyl-morpholine-4-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3-ethyl-4-methyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [3-(3-{4-[2-(4-Acetyl-3-ethyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-carbamic acid methyl ester; [3-(3-{4-[2-(4-Acetyl-3-ethyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3-ethyl-4-ethylcarbamoyl-piperazin-1-ylmethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3-ethyl-4-ethylcarbamoyl-piperazine-1-carbonyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; 4-(4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-ylmethyl)-2-ethyl-piperazine-1-carboxylic acid tert-butyl ester; 4-(4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalen-1-yloxy}-pyridine-2-carbonyl)-2-ethyl-piperazine-1-carboxylic acid tert-butyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-oxazol-5-yl-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-oxazol-5-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-methyl-3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [3-(3-{4-[2-(3-Benzyl-3H-imidazol-4-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-carbamic acid methyl ester; {5-tert-Butyl-2-methoxy-3-[3-(4-{2-[3-(2-morpholin-4-yl-ethyl)-3H-imidazol-4-yl]-pyridin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-phenyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; 2-(4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalen-1-yloxy}-pyridin-2-yl)-thiazole-4-carboxylic acid ethyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-methylcarbamoyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-dimethylcarbamoyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; {5-tert-Butyl-3-[3-(4-{2-[4-(2-diethylamino-ethylcarbamoyl)-thiazol-2-yl]-pyridin-4-yloxy}-naphthalen-1-yl)-ureido]-2-methoxy-phenyl}-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(4-dimethylaminomethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-pyrrolidin-1-ylmethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(4-morpholin-4-ylmethyl-thiazol-2-yl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(pyridin-4-yloxy)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenoxy-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenoxy-pyridin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-pyridin-4-yloxy)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(1-hydroxy-ethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(hydroxy-phenyl-methyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; N-[5-tert-Butyl-3-(3-{4-[2-(hydroxy-phenyl-methyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(1-hydroxy-ethyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; [5-tert-Butyl-3-(3-{4-[2-(3-diethylamino-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-morpholin-4-yl-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-pyrrolidin-1-yl-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; N-[5-tert-Butyl-3-(3-{4-[2-(3-diethylamino-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-morpholin-4-yl-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(3-pyrrolidin-1-yl-propenyl)-pyridin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; 3-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-N-methyl-benzamide; 3-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalen-1-yloxy}-N,N-dimethyl-benzamide; (5-tert-Butyl-2-methoxy-3-{3-[4-(3-methylcarbamoyl-phenoxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-3-{3-[4-(3-dimethylcarbamoyl-phenoxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5-tert-Butyl-2-methoxy-3-{3-[4-(3-oxazol-5-yl-phenoxy)-naphthalen-1-yl]-ureido}-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[3-(4-methyl-oxazol-5-yl)-phenoxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(3-oxazol-5-yl-phenoxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[3-(4-methyl-oxazol-5-yl)-phenoxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-dimethylaminomethyl-pyridin-4-yl)-methyl)naphthalen-1-yl]ureido}-2-methoxyphenyl]methanesulfonamide and N-(5-tert-Butyl-3-{3-[4-(2-methanesulfinyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(3-{3-[4-(2-Amino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-(3-{3-[4-(2-Benzylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(1-(R)-phenyl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(1-(S)-phenyl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-isobutylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-methylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide N-(5-tert-Butyl-3-{3-[4-(2-ethylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-isopropylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido }-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-propylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide N-[5-tert-Butyl-3-(3-{4-[2-(cyclopentylmethyl-amino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(thiophen-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-{5-tert-Butyl-3-[3-(4-{2-[(furan-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-2-methoxy-phenyl}-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(2-methoxy-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-butylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenethylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(pyridin-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(pyridin-3-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-cyclopentylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-cyclohexylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-morpholin-4-yl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-dimethylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-[3-(3-{4-[2-(Benzyl-methyl-amino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-5-tert-butyl-2-methoxy-phenyl]-methanesulfonamide N-{5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(pyridin-4-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide N-(5-tert-Butyl-3-{3-[4-(2-diethylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-pyrrolidin-1-yl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; (3-{3-[4-(2-Benzylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(1-(R)-phenyl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-(1-(S)-phenyl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(cyclopropylmethyl-amino)-pyrimidin-4-yloxy]-naphthalen-1-yl}ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; {5-tert-Butyl-2-methoxy-3-[3-(4-{2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-carbamic acid methyl ester; (3-{3-[4-(2-Amino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-carbamic acid methyl ester; 1-[4-(2-Amino-pyrimidin-4-yloxy)-naphthalen-1-yl]-3-[5-tert-butyl-3-(4,5-dihydro-oxazol-2-ylamino)-2-methoxy-phenyl]-urea; 1-[5-tert-Butyl-3-(4,5-dihydro-oxazol-2-ylamino)-2-methoxy-phenyl]-3-{4-[2-(1-phenyl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-urea; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[2-(2-methoxy-ethylamino)-6-methyl-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(2-dimethylamino-ethylamino)-6-methyl-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[6-methyl-2-(2-pyrrolidin-1-yl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[6-methyl-2-(2-morpholin-4-yl-ethylamino)-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-methyl-2-pyrrolidin-1-yl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[2-(2-dimethylamino-ethoxy)-6-methyl-pyrimidin-4-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenoxy-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-isopropylamino-6-methyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-methanesulfonylamino-6-methyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-isobutylamino-6-methyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-{5-tert-Butyl-2-methoxy-3-[3-(4-{6-methyl-2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-yloxy}-naphthalen-1-yl)-ureido]-phenyl}-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-methyl-2-methylamino-pyrimidin-4-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(4-methylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-dimethylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-ethylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-isobutylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(3-{3-[4-(4-Benzylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide; (R)-N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-(1-phenyl-ethylamino)-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; (S)-N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-(1-phenyl-ethylamino)-[1,3,5]triazin2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-(2-morpholin-4-yl-ethylamino)-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-dimethylamino-6-methoxy-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(4-methoxy-6-pyrrolidin-1-yl-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-ethoxy-6-methylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N(5-tert-Butyl-3-{3-[4-(4-isobutylamino-6-methoxy-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(3-{3-[4-(4-Benzylamino-6-methoxy-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-isopropylamino-6-methoxy-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(4-isopropoxy-6-methylamino-[1,3,5]triazin-2-yloxy)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[4-(2-dimethylamino-ethoxy)-6-methoxy-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[4-(2-dimethylamino-ethylamino)-6-methoxy-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-methoxy-6-(2-pyrrolidin-1-yl-ethylamino)-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-methoxy-6-(2-morpholin-4-yl-ethylamino)-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[4-methoxy-6-(2-methoxy-ethylamino)-[1,3,5]triazin-2-yloxy]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; (4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalene-1-carbonyl}-6-hydroxymethyl-6-methyl-morpholin-2-yl)-acetic acid methyl ester; (4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalene-1-carbonyl}-6-hydroxymethyl-6-methyl-morpholin-2-yl)-acetic acid methyl ester; (4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalene-1-carbonyl}-6-hydroxymethyl-6-phenyl-morpholin-2-yl)-acetic acid methyl ester; (4-{4-[3-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl)-ureido]-naphthalene-1-carbonyl}-6-hydroxymethyl-6-phenyl-morpholin-2-yl)-acetic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(2-hydroxy-ethyl)-2-phenyl-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-3-(3-{4-[2-(2-hydroxy-ethyl)-2-phenyl-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-2-methoxy-phenyl]-methanesulfonamide; (4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalene-1-carbonyl}-6-phenyl-morpholin-2-yl)-acetic acid methyl ester; (4-{4-[3-(5-tert-Butyl-2-methoxy-3-methoxycarbonylamino-phenyl)-ureido]-naphthalene-1-carbonyl}-6-phenyl-morpholin-2-yl)-methanesulfonamide; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-phenyl-6-(1H-pyrrol-3-yl)-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-phenyl-6-(1H-indol-3-yl)-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-phenyl-6-(1H-indol-3-yl)-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-phenyl]-carbamic acid methyl ester; [5-tert-Butyl-2-methoxy-3-(3-{4-[2-phenyl-6-(1H-pyrrol-3-yl)-morpholine-4-carbonyl]-naphthalen-1-yl}-ureido)-phenyl]-methanesulfonamide; (5-tert-Butyl-3-{3-[4-(6,7-diphenoxy-8-oxa-3-aza-bicyclo[3.2.1]octane-3-carbonyl)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-carbamic acid methyl ester; (5tert-Butyl-3-{3-[4-(6,7-diphenoxy-8-oxa-3-aza-bicyclo [3.2.1]octane-3-carbonyl)-naphthalen-1-yl]-ureido}-2-methoxy-phenyl)-methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenyl-1-pyridin-4-yl-ethyl)naphthalen-1-yl]ureido}phenyl)methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenyl-1-(2-dimethylaminomethyl)pyridin-4-yl-ethyl)naphthalen-1-yl]ureido}phenyl)methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[(1-methylpiperdin-4-yl)-tetrahyrdopyran-4-yl)methyl]naphthalen-1-yl}ureido)phenyl]methanesulfonamide; N-[5-tert-Butyl-2-methoxy-3-(3-{4-[(1-methylpiperdin-4-yl)-(morpholin-4-yl)methyl]naphthalen-1-yl}ureido)phenyl]methanesulfonamide; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(2-phenyl-1-(2-(methylaminocarbonyl)morpholin-4-yl)ethyl)naphthalen-1-yl]ureido}phenyl)methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[(2-dimethylamino-pyridin-4-yl)-morpholin-4-yl-methyl]naphthalen-1-yl}ureido)-2-methoxyphenyl]methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[(2-dimethylamino-pyridin-4-yl)-imidazol-1-yl-methyl]naphthalen-1-yl}ureido)-2-methoxyphenyl]methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(imidazol-1-yl-pyridin-4-yl)methyl]naphthalen-1-yl]ureido}-2-methoxyphenyl)methanesulfonamide; N-(5-tert-Butyl-3-{3-[4-(2-dimethylamino-pyridin-4-yl)-methyl)naphthalen-1-yl]ureido}-2-methoxyphenyl]methanesulfonamide; N-[5-tert-Butyl-3-(3-{4-[(2-dimethylaminomethyl-pyridin-4-yl)-piperazin-1-yl-methyl]naphthalen-1-yl}ureido)-2-methoxyphenyl]methanesulfonamide and the pharmaceutically acceptable derivatives thereof.
- 32. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 1.
- 33. A method of treating a cytokine mediated disease or condition which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1.
- 34. The method according to claim 33 wherein cytokine mediated disease or condition is selected from rheumatoid arthritis, osteoarthritis, Crohn's disease, ulcerative colitis, multiple sclerosis, Guillain-Barre syndrome, psoriasis, graft versus host disease, systemic lupus erythematosus, diabetes, toxic shock syndrome, Alzheimer's disease, acute and chronic pain, contact dermatitis, atherosclerosis, traumatic arthritis, glomerulonephritis, reperfusion injury, sepsis, bone resorption diseases, chronic obstructive pulmonary disease, congestive heart failure, asthma, stroke, myocardial infarction, thermal injury, adult respiratory distress syndrome (ARDS), multiple organ injury secondary to trauma, dermatoses with acute inflammatory components, acute purulent meningitis, necrotizing entrerocolitis and syndromes associated with hemodialysis, leukopherisis and granulocyte transfusion.
- 35. The method according to claim 34 wherein the disease is selected from rheumatoid arthritis, osteoarthritis, Crohn's disease, psoriasis, ulcerative colitis, osteoporosis, chronic obstructive pulmonary disease and congestive heart failure.
- 36. The method according to claim 35 wherein the disease is selected from rheumatoid arthritis, Crohn's disease, psoriasis, chronic obstructive pulmonary disease and congestive heart failure.
- 37. A method of making a compound of the formula(I):
RELATED APPLICATION DATA
[0001] This application claims benefit to U.S. provisional application No. 60/283,642 filed Apr. 13, 2001.
Provisional Applications (1)
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Number |
Date |
Country |
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60283642 |
Apr 2001 |
US |
Patent Application
20030083333
