US 2003/0083333 A1Published application

1,4-Disubstituted benzo-fused compounds

AssigneeBoehringer Ingelheim Pharmaceuticals, Inc.

InventorsPier Francesco Cirillo, Daniel R. Goldberg, Abdelhakim Hammach, Neil Moss, Kristen Mueller, John Robinson Regan

Life of this patent

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Abstract

Disclosed are novel 1,4-disubstituted benzo-fused compounds wherein G, X, L, Q, n and Y are defined herein. The compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are processes of making such compounds. 1

Claims37

Dependent claims

A 1,4-disubstituted benzo-fused compound of the formula (I):

282
wherein:
ring A is:
fused saturated or unsaturated ring containing 3-5 carbon atoms wherein ring A or the phenyl ring to which it is fused is optionally substituted by one or more a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-6 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl, phenylsulfonyl, hydroxy, amino, mono- or di-(C1-4 alkyl)amino, mono- or di-(C1-4 alkyl)amino-S(O)2, cyano, nitro or H2NSO2;
G is:
phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl, benzocycloheptenyl, indanyl, indenyl;
pyridinyl, pyridonyl, quinolinyl, dihydroquinolinyl, tetrahydroquinoyl, isoquinolinyl, tetrahydroisoquinoyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dibenzofuranyl, dihydrobenzothiophenyl, benzooxazolonyl, benz[1,4]oxazin-3-onyl, benzodioxolyl, benz[1,3]dioxol-2-onyl, benzofuran-3-onyl, tetrahydrobenzopyranyl, indolyl, 2,3-dihydro-1H-indolyl, indolinyl, indolonyl, indolinonyl, phthalimidyl, chromonyl;
oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, dioxanyl, tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, thiazolinyl, imidazolinyl, tertrahydropyridinyl, homopiperidinyl, pyrrolinyl, tetrahydropyrimidinyl, decahydroquinolinyl, decahydroisoquinolinyl, thiomorpholinyl, thiazolidinyl, dihydrooxazinyl, dihydropyranyl, oxocanyl, heptacanyl, thioxanyl or dithianyl;
wherein G is substituted by one R3 and further substituted by one or more R1 or R2;
L is:
a) —O—;
—NH—;
>C(O);
>C(S);
C1-10 saturated or unsaturated branched or unbranched carbon chain;
wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m;
and
wherein said L is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino;
or
b) >CRxRy wherein Rx and Ry are each independently hydrogen, C1-4alkyl, heterocycleC0-4 alkyl, heteroarylC0-4 alkyl or arylC0-4 alkyl;
Q is:
phenyl, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, benzimidazolyl, furanyl, thienyl, pyranyl, thiazolyl, oxazolyl, naphthyridinyl, pyrazinyl, pyrazolyl, triazolyl, tetrazolyl, pyrazolo[3,4-b]pyrimidinyl, purinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, tubercidinyl, oxazo[4,5-b]pyridinyl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1]heptanyl, imidazo[4,5-b]pyridinyl, 1-oxo-λ4-thiomorpholinyl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene which are optionally substituted with one to three C1-6 alkyl, phenyl, C1-6 alkoxy or hydroxy;
tetrahydropyranyl, 2-oxo-2H-pyranyl, tetrahydrofuranyl, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, piperazinyl, piperidinyl, piperidinonyl, tetrahydropyrimidonyl, cyclohexanone, cyclohexanol, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide or tetramethylene sulfone each optionally substituted with one to three C1-6 alkyl, phenyl, C1-6 alkoxy or hydroxy;
or Q is C1-6 alkoxy, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to C1-3 alkyl or C1-5 alkoxyalkyl, phenylamino, wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy, hydroxy or mono- or di-(C1-3 alkyl)amino, C1-6 alkyl-S(O)m or phenyl-S(O)m wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy, hydroxy or mono- or di-(C1-3 alkyl)amino;
R1 is independently:
C3-10 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-10 cycloalkyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl;
each of the aforementioned being optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C3-8 cycloalkyl, C5-8 cycloalkenyl, hydroxy, cyano, C1-3 alkoxy which is optionally partially or fully halogenated and NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, which are 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 aryl;
C3-10 branched or unbranched alkenyl optionally partially or fully halogenated, and optionally substituted with one to three C1-5 branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl, each of the aforementioned are optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, hydroxy, cyano, C1-3 alkoxy optionally partially or fully halogenated, NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C1-3 alkyl groups;
N-morpholinyl;
cyano, halogen;
methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl;
silyl containing three C1-4 independently branched or unbranched alkyl groups optionally partially or fully halogenated;
C1-6 branched or unbranched alkyl-C(O), C1-6 branched or unbranched-S(O)m;
C2-6 alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH and S(O)m and wherein said alkynyl group is optionally independently substituted with 0-2 oxo groups, pyrrolidinyl, pyrrolyl, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, nitrile, morpholinyl, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or C1-4 branched or unbranched alkylamino optionally substituted by one or more halogen atoms;
R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-4 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl;
hydroxy, amino, or mono- or di-(C1-4 alkyl)amino, cyano, halogen;
OR5;
nitro;
or
mono- or di-(C1-4 alkyl)amino-S(O)2 optionally partially or fully halogenated, or H2NSO2;
each R3 is independently:
(J)p—L′—S(O)m—NH— or (J)p—L′—O—C(O)—NH—,
wherein for R3:
L′ is a bond or
C1-10 saturated or unsaturated branched or unbranched carbon chain;
wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m;
and
wherein said L′ is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino;
J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl;
cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl;
phenyl, naphthyl, morpholinyl, pyridinyl, piperidinyl, piperazinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazoyl, [1,3,4]oxadiazol, triazolyl, tetrazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl,
or J is a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl, cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl, cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl, cyclohexanoquinolinyl, cyclopentanoisoquinolinyl, cyclohexanoisoquinolinyl, cyclopentanoindolyl, cyclohexanoindolyl, cyclopentanobenzimidazolyl, cyclohexanobenzimidazolyl, cyclopentanobenzoxazolyl, cyclohexanobenzoxazolyl, cyclopentanoimidazolyl, cyclohexanoimidazolyl, cyclopentanothienyl and cyclohexanothienyl;
each J is optionally substituted by one to three R4;
each R4 is independently
C1-6 alkyl, arylC0-6 alkyl, heterocycleC0-6 alkyl, heteroarylC0-6 alkyl each optionally substituted by halogen, hydroxy, carboxy, oxo, nitro or nitrile, or R4 is amino optionally mono- or di-substituted by C1-6 alkyl, C0-6 alkylaryl, C0-6 alkylheterocycle or C0-6 alkylheteroaryl, halogen, hydroxy, carboxy, oxo, nitro or nitrile;
wherein if p is 0, then L′ cannot be a bond;
each R5 or R6 is independently:
hydrogen, arylC0-3 alkyl optionally substituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, or R5 or R6 are C1-3 acyl, aroyl or C1-6 branched or unbranched alkyl optionally substituted by C1-5 alkoxy, hydroxy, mono- or di-C1-3alkylaminocarbonyl or mono or diC,3 alkyl amino wherein said C1-6 alkyl optionally partially or fully halogenated;
or R5 and R6 taken together optionally form a heterocyclic or heteroaryl ring;
Y, which covalently attached to Q, is
a bond, —O—, >C(O), —NH—, —C(O)—NH—, —S—, C1-5 alkyl branched or unbranched, C1-3 alkyl(OH), C2-5 alkenyl, C1-3 acyl, heterocycle selected from morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl or tetrahydrofuryl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, quinoxalinyl, quinazolinyl or indazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-4 acyl, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—;
wherein each Y is optionally further covalently attached to NR5R6, C1-4 alkyl, C3-7 cycloalkylC0-4 alkyl, C1-4 alkoxy, aryloxy, hydroxy, arylC0-4 alkyl, heteroarylC0-4 alkyl or heterocycleC0-4 alkyl as wherein the heteroaryl and heterocycle moieties are as hereinabove described for Y and the heterocycle, heteroaryl and aryl moieties are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C13 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—;
m, n and p are each independently 0, 1 or 2;
X is O or S;
and
the pharmaceutically acceptable derivatives thereof.

67 more elements

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.

247 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/120,028Filed 10 Apr 2002
Priority: 13 Apr 2001
Published: 1 May 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07D 213/79
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: acids; Esters
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/04
Drugs for disorders of the cardiovascular system: inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Family

Application60/283,642Us provisional application · filed 13 Apr 2001
US 6,765,009 B2Related patent
US 2003/0083333 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A 1,4-disubstituted benzo-fused compound of the formula (I):

282
wherein:
ring A is:
fused saturated or unsaturated ring containing 3-5 carbon atoms wherein ring A or the phenyl ring to which it is fused is optionally substituted by one or more a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-6 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl, phenylsulfonyl, hydroxy, amino, mono- or di-(C1-4 alkyl)amino, mono- or di-(C1-4 alkyl)amino-S(O)2, cyano, nitro or H2NSO2;
G is:
phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl, benzocycloheptenyl, indanyl, indenyl;
pyridinyl, pyridonyl, quinolinyl, dihydroquinolinyl, tetrahydroquinoyl, isoquinolinyl, tetrahydroisoquinoyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl, benzopyrazolyl, dihydrobenzofuranyl, dibenzofuranyl, dihydrobenzothiophenyl, benzooxazolonyl, benz[1,4]oxazin-3-onyl, benzodioxolyl, benz[1,3]dioxol-2-onyl, benzofuran-3-onyl, tetrahydrobenzopyranyl, indolyl, 2,3-dihydro-1H-indolyl, indolinyl, indolonyl, indolinonyl, phthalimidyl, chromonyl;
oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, dioxanyl, tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, thiazolinyl, imidazolinyl, tertrahydropyridinyl, homopiperidinyl, pyrrolinyl, tetrahydropyrimidinyl, decahydroquinolinyl, decahydroisoquinolinyl, thiomorpholinyl, thiazolidinyl, dihydrooxazinyl, dihydropyranyl, oxocanyl, heptacanyl, thioxanyl or dithianyl;
wherein G is substituted by one R3 and further substituted by one or more R1 or R2;
L is:
a) —O—;
—NH—;
>C(O);
>C(S);
C1-10 saturated or unsaturated branched or unbranched carbon chain;
wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m;
and
wherein said L is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino;
or
b) >CRxRy wherein Rx and Ry are each independently hydrogen, C1-4alkyl, heterocycleC0-4 alkyl, heteroarylC0-4 alkyl or arylC0-4 alkyl;
Q is:
phenyl, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, benzimidazolyl, furanyl, thienyl, pyranyl, thiazolyl, oxazolyl, naphthyridinyl, pyrazinyl, pyrazolyl, triazolyl, tetrazolyl, pyrazolo[3,4-b]pyrimidinyl, purinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, tubercidinyl, oxazo[4,5-b]pyridinyl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, 2-thia-5-aza-bicyclo[2.2.1]heptanyl, imidazo[4,5-b]pyridinyl, 1-oxo-λ4-thiomorpholinyl or 13-oxa-11-aza-tricyclo[7.3.1.0-2,7]trideca-2,4,6-triene which are optionally substituted with one to three C1-6 alkyl, phenyl, C1-6 alkoxy or hydroxy;
tetrahydropyranyl, 2-oxo-2H-pyranyl, tetrahydrofuranyl, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, piperazinyl, piperidinyl, piperidinonyl, tetrahydropyrimidonyl, cyclohexanone, cyclohexanol, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide or tetramethylene sulfone each optionally substituted with one to three C1-6 alkyl, phenyl, C1-6 alkoxy or hydroxy;
or Q is C1-6 alkoxy, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to C1-3 alkyl or C1-5 alkoxyalkyl, phenylamino, wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy, hydroxy or mono- or di-(C1-3 alkyl)amino, C1-6 alkyl-S(O)m or phenyl-S(O)m wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy, hydroxy or mono- or di-(C1-3 alkyl)amino;
R1 is independently:
C3-10 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-10 cycloalkyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl;
each of the aforementioned being optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C3-8 cycloalkyl, C5-8 cycloalkenyl, hydroxy, cyano, C1-3 alkoxy which is optionally partially or fully halogenated and NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, which are 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 aryl;
C3-10 branched or unbranched alkenyl optionally partially or fully halogenated, and optionally substituted with one to three C1-5 branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl, each of the aforementioned are optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, hydroxy, cyano, C1-3 alkoxy optionally partially or fully halogenated, NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C1-3 alkyl groups;
N-morpholinyl;
cyano, halogen;
methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl;
silyl containing three C1-4 independently branched or unbranched alkyl groups optionally partially or fully halogenated;
C1-6 branched or unbranched alkyl-C(O), C1-6 branched or unbranched-S(O)m;
C2-6 alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH and S(O)m and wherein said alkynyl group is optionally independently substituted with 0-2 oxo groups, pyrrolidinyl, pyrrolyl, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, nitrile, morpholinyl, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or C1-4 branched or unbranched alkylamino optionally substituted by one or more halogen atoms;
R2 is independently:
a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-4 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl;
hydroxy, amino, or mono- or di-(C1-4 alkyl)amino, cyano, halogen;
OR5;
nitro;
or
mono- or di-(C1-4 alkyl)amino-S(O)2 optionally partially or fully halogenated, or H2NSO2;
each R3 is independently:
(J)p—L′—S(O)m—NH— or (J)p—L′—O—C(O)—NH—,
wherein for R3:
L′ is a bond or
C1-10 saturated or unsaturated branched or unbranched carbon chain;
wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m;
and
wherein said L′ is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino;
J is:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl;
cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl;
phenyl, naphthyl, morpholinyl, pyridinyl, piperidinyl, piperazinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazoyl, [1,3,4]oxadiazol, triazolyl, tetrazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl,
or J is a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl, cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl, cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl, cyclohexanoquinolinyl, cyclopentanoisoquinolinyl, cyclohexanoisoquinolinyl, cyclopentanoindolyl, cyclohexanoindolyl, cyclopentanobenzimidazolyl, cyclohexanobenzimidazolyl, cyclopentanobenzoxazolyl, cyclohexanobenzoxazolyl, cyclopentanoimidazolyl, cyclohexanoimidazolyl, cyclopentanothienyl and cyclohexanothienyl;
each J is optionally substituted by one to three R4;
each R4 is independently
C1-6 alkyl, arylC0-6 alkyl, heterocycleC0-6 alkyl, heteroarylC0-6 alkyl each optionally substituted by halogen, hydroxy, carboxy, oxo, nitro or nitrile, or R4 is amino optionally mono- or di-substituted by C1-6 alkyl, C0-6 alkylaryl, C0-6 alkylheterocycle or C0-6 alkylheteroaryl, halogen, hydroxy, carboxy, oxo, nitro or nitrile;
wherein if p is 0, then L′ cannot be a bond;
each R5 or R6 is independently:
hydrogen, arylC0-3 alkyl optionally substituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, or R5 or R6 are C1-3 acyl, aroyl or C1-6 branched or unbranched alkyl optionally substituted by C1-5 alkoxy, hydroxy, mono- or di-C1-3alkylaminocarbonyl or mono or diC,3 alkyl amino wherein said C1-6 alkyl optionally partially or fully halogenated;
or R5 and R6 taken together optionally form a heterocyclic or heteroaryl ring;
Y, which covalently attached to Q, is
a bond, —O—, >C(O), —NH—, —C(O)—NH—, —S—, C1-5 alkyl branched or unbranched, C1-3 alkyl(OH), C2-5 alkenyl, C1-3 acyl, heterocycle selected from morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl or tetrahydrofuryl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, quinoxalinyl, quinazolinyl or indazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-4 acyl, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—;
wherein each Y is optionally further covalently attached to NR5R6, C1-4 alkyl, C3-7 cycloalkylC0-4 alkyl, C1-4 alkoxy, aryloxy, hydroxy, arylC0-4 alkyl, heteroarylC0-4 alkyl or heterocycleC0-4 alkyl as wherein the heteroaryl and heterocycle moieties are as hereinabove described for Y and the heterocycle, heteroaryl and aryl moieties are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C13 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6—C(O)—;
m, n and p are each independently 0, 1 or 2;
X is O or S;
and
the pharmaceutically acceptable derivatives thereof.

67 more elements

Facts

Application

10/120,028Filed 10 Apr 2002

Priority

13 Apr 2001

Published

1 May 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07D 213/79
Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals: acids; Esters
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/04
Drugs for disorders of the cardiovascular system: inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure