US2004152725A1PendingUtilityA1
Methods of treating cancer
Assignee: BOEHRINGER INGELHEIM PHARMAPriority: Jul 11, 2001Filed: Jan 20, 2004Published: Aug 5, 2004
Est. expiryJul 11, 2021(expired)· nominal 20-yr term from priority
A61P 9/04A61P 9/10A61P 7/00A61P 37/00A61P 9/00A61P 35/00A61P 29/00A61P 27/02A61P 25/28A61P 15/00A61P 1/18A61K 31/216A61P 11/00A61K 31/435A61P 19/08A61P 19/02A61K 31/415A61K 31/5377
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Claims
Abstract
Disclosed are methods of treating certain cytokine mediated diseases or conditions using novel aromatic heterocyclic compounds of the formula(I) wherein Ar 1 , Ar 2 , L, Q and X are described herein.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating cancer said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula (I):
wherein
Ar 1 is a heterocyclic group selected from the group consisting of pyrrole, pyrrolidine, pyrazole, imidazole, oxazole, thiazole, furan and thiophene; and wherein Ar 1 may be substituted by one or more R 1 , R 2 or R 3 ;
Ar 2 is:
phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl or indole each being optionally substituted with one to three R 2 groups;
L is a C 1-10 saturated or unsaturated branched or unbranched carbon chain;
wherein one or more methylene groups are optionally independently replaced by O, N or S; and
wherein said linking group is optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms;
Q is selected from the group consisting of:
a) phenyl, naphthyl, pyridine, pyrimidine, pyridazine, imidazole, benzimidazole, furan, thiophene, pyran, naphthyridine, oxazo[4,5-b]pyridine and imidazo[4,5-b]pyridine, which are optionally substituted with one to three groups selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, hydroxy, mono- or di-(C 1-3 alkyl)amino, C 1-6 alkyl-S(O) m and phenylamino wherein the phenyl ring is optionally substituted with one to two groups consisting of halogen, C 1-6 alkyl and C 1-6 alkoxy;
b) tetrahydropyran, tetrahydrofuran, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine sulfoxide, thiomorpholine sulfone, piperidine, piperidinone, tetrahydropyrimidone, cyclohexanone, cyclohexanol, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide and tetramethylene sulfone which are optionally substituted with one to three groups selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, mono- or di-(C 1-3 alkyl)amino-C 1-3 alkyl, phenylamino-C 1-3 alkyl and C 1-3 alkoxy-C 1-3 alkyl;
c) C 1-6 alkoxy, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to groups selected from the group consisting of C 1-3 alkyl and C 1-5 alkoxyalkyl and phenyl, wherein the phenyl ring is optionally substituted with one to two groups selected from the group consisting of halogen, C 1-6 alkoxy, hydroxy or mono- or di-(C 1-3 alkyl)amino, C 1-6 alkyl-S(O) r , phenyl-S(O) t , wherein the phenyl ring is optionally substituted with one to two groups selected from the group consisting of halogen, C 1-6 alkoxy, hydroxy or mono- or di-(C 1-3 alkyl)amino;
R 1 is selected from the group consisting of:
a) C 3-10 branched or unbranched alkyl, which may optionally be partially or fully halogenated, and optionally substituted with one to three phenyl, naphthyl or heterocyclic groups selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl; each such phenyl, naphthyl or heterocycle selected from the group hereinabove described, being substituted with 0 to 5 groups selected from the group consisting of halogen, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, hydroxy, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, NH 2 C(O) and di(C 1-3 )alkylaminocarbonyl;
b) C 3-7 cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which may optionally be partially or fully halogenated and which may optionally be substituted with one to three C 1-3 alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from O, S, CHOH, >C═O, >C═S and NH;
c) C 3-10 branched alkenyl which may optionally be partially or fully halogenated, and which is optionally substituted with one to three C 1-5 branched or unbranched alkyl, phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each such phenyl, naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from halogen, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, hydroxy, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, NH 2 C(O), mono- or di(C 1-3 )alkylaminocarbonyl;
d) C 5-7 cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group may optionally be substituted with one to three C 1-3 alkyl groups;
e) cyano; and,
f) methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl;
R 2 is selected from the group consisting of:
a C 1-6 branched or unbranched alkyl which may optionally be partially or fully halogenated, acetyl, aroyl, C 1-4 branched or unbranched alkoxy, which may optionally be partially or fully halogenated, halogen, methoxycarbonyl and phenylsulfonyl;
R 3 is selected from the group consisting of:
a) a phenyl, naphthyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl; wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a C 1-6 branched or unbranched alkyl, phenyl, naphthyl, heterocycle selected from the group hereinabove described, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C 1-5 alkyl, naphthyl C 1-5 alkyl, halo, hydroxy, cyano, C 1-3 alkyloxy which may optionally be partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described, nitro, amino, mono- or di-(C 1-3 )alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described, NH 2 C(O), a mono- or di-(C 1-3 )alkyl aminocarbonyl, C 1-5 alkyl-C(O)—C 1-4 alkyl, amino-C 1-5 alkyl, mono- or di-(C 1-3 )alkylamino-C 1-5 alkyl, amino-S(O) 2 , di-(C 1-3 )alkylamino-S(O) 2 , R 4 —C 1-5 alkyl, R 5 —C 1-5 alkoxy, R 6 —C(O)—C 1-5 alkyl and R 7 —C 1-5 alkyl(R 8 )N;
b) a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heterocyclyl selected from the group consisting of cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, and isothiazolyl, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, halo, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described, nitro, amino, mono- or di-(C 1-3 )alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described, NH 2 C(O), a mono- or di-(C 1-3 )alkyl aminocarbonyl, C 1-4 alkyl-OC(O), C 1-5 alkyl-C(O)—C 1-4 branched or unbranched alkyl, an amino-C 1-5 alkyl, mono- or di-(C 1-3 )alkylamino-C 1-5 alkyl, R 9 —C 1-5 alkyl, R 10 —C 1-5 alkoxy, R 11 —C(O)—C 1-5 alkyl and R 12 —C 1-5 alkyl(R 13 )N;
c) cycloalkyl selected from the group consisting of cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which the cycloalkyl may optionally be partially or fully halogenated and which may optionally be substituted with one to three C 1-3 alkyl groups;
d) C 5-7 cycloalkenyl, selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group may optionally be substituted with one to three C 1-3 alkyl groups; and
e) acetyl, aroyl, alkoxycarbonylalkyl or phenylsulfonyl;
f) C 1-6 branched or unbranched alkyl which may optionally be partially or fully halogenated;
wherein
or R 1 and R 2 taken together may optionally form a fused phenyl or pyridinyl ring,
each R 8 , R 13 is independently selected from the group consisting of:
hydrogen and C 1-4 branched or unbranched alkyl which may optionally be partially or fully halogenated;
each R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R 11 and R 12 is independently selected from the group consisting of:
morpholine, piperidine, piperazine, imidazole and tetrazole;
m=0, 1, 2;
r=0, 1, 2;
t=0, 1, 2; and
X═O or S or
the physiologically acceptable acids or salts thereof.
2 . The method according to claim 1 wherein Ar 2 is naphthyl, tetrahydronaphthyl, indanyl or indenyl.
3 . The method according to claim 2 wherein Ar 2 is naphthyl.
4 . The method according to claim 3 wherein:
Ar 1 is thiophene or pyrazole;
Ar 2 is 1-naphthyl;
L is C 1-6 saturated or unsaturated branched or unbranched carbon chain wherein one or more methylene groups are optionally independently replaced by O, N or S; and
wherein said linking group is optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms;
R 1 is selected from the group consisting of C 3-10 alkyl branched or unbranched, cyclopropyl and cyclohexyl which may optionally be partially or fully halogenated and which may optionally be substituted with one to three C 1-3 alkyl groups;
R 3 is selected from the group consisting of C 1-4 alkyl branched or unbranched, cyclopropyl, cyclopentyl, phenyl, pyridinyl each being optionally substituted as described in claim 1 and alkoxycarbonylalkyl.
5 . The method according to claim 4 wherein Ar, is pyrazole.
6 . The method according to claim 5 wherein L is C 1-5 saturated carbon chain wherein one or more methylene groups are optionally independently replaced by O, N or S; wherein said linking group is optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms; and
X═O.
7 . The method according to claim 6 wherein L is propoxy, ethoxy or methoxy each being optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms.
8 . The method according to claim 7 wherein L is ethoxy optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms.
9 . The method according to claim 6 wherein L is methyl or propyl each being optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms.
10 . The method according to claim 6 wherein L is C 3-5 acetylene optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms.
11 . The method according to claim 6 wherein L is methylamino optionally substituted with 0-2 oxo groups and one or more C 1-4 branched or unbranched alkyl which may be substituted by one or more halogen atoms.
12 . The method according to claim 1 wherein the compound is chosen from:
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(cis-2,6-dimethylmorpholin-4-yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(trans-2,6-dimethylmorpholin-4-yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(2-(methoxymethyl)morpholin-4-yl)-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl)-2-oxoethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl)-2-methylethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl)-1-methylethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-thiomorpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(1-oxothiomorpholin-4-yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)-3-methylnaphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl-carbonyloxo)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(tetrahydropyran-4yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(1-oxo-tetrahydrothiophen-3-yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-morpholin-4-yl-propyl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(morpholin-4-yl-methyl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-pyridin-4-yl-ethyl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(morpholin-4-yl)propyn-1-yl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(tetrahydropyran-2-yl-oxy)propyn-1-yl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(tetrahydropyran-2-yl-oxy)butyn-1-yl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(piperdin-1-yl)propyn-1-yl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(2-methoxymethylmorpholin-4-yl)propyn-1-yl)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yl-methoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-pyridin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-pyridin-4-yl-propoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-imidazol-1-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(3,4-dimethoxyphenyl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yl-methylamino)naphthalen-1-yl]-urea;
1-[5-iso-Propyl-2-phenyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-cyclohexyl-2-phenyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-(2,2,2-trifluoroethyl)-2-phenyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-(1-methylcycloprop-1-yl)-2-phenyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-(1-methylcyclohex-1-yl)-2-phenyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-methyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(4-chlorophenyl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(4-methyl-3-carbamylphenyl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(4-methyl-3-(morpholin-4-yl)methylphenyl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(4-methyl-3-dimethylaminomethylphenyl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(3-dimethylaminomethylphenyl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-chloropyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methylpyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methoxypyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methylpyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-pyridin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methylpyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-(trans-2,6-dimethylmorpholin-4-yl)ethoxy)naphthalen-1-yl]-urea and
1-[5-tert-butyl-2-(2-methylpyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(3-morpholin-4-yl-propyn-1-yl)naphthalen-1-yl]-urea
or the physiologically acceptable acids or salts thereof.
13 . The method according to claim 12 wherein the compound is chosen from the group consisting of:
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(1-oxothiomorpholin-4yl)ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methylpyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-pyridin-4-yl-ethoxy)naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(2-methoxypyridin-5-yl]-2H-pyrazol-3-yl-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea and
1-[5-tert-butyl-2-methyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea
or the physiologically acceptable acids or salts thereof.
14 . The method according to claim 13 wherein the compound is:
1-[5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea
or the physiologically acceptable acids or salts thereof.
15 . The method according to claim 1 wherein the disease is cancer and the treatment is done in conjunction with genotoxic therapy.
16 . A method of treating cancer said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound chosen from
1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(3-hydroxy-4-methyl-phenyl)-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-[2-(3-oxo-morpholin-4-
yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-[2-(4-oxy-morpholin-4-
yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-2-(6-methyl-pyridin-3-yl)-2H-
pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl)-2-(1-oxy-6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-[2-(4-
oxy-morpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-2-(6-methyl-pyridin-3-yl)-2H-
pyrazol-3-yl]-3-[4-(2-pyridin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(2-
hydroxy-2-pyridin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-[2-(1-
oxy-pyridin-4-yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-[2-
(1-oxo-thiomorpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-tert-butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{4-[2-(1-
oxo-thiomorpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-[2-(1,3 dioxo-
thiomorpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-2-methyl-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
1-[5-tert-butyl-2-methyl-2H-pyrazol-3-yl]-3-{4-[2-(4-oxy-morpholin-4-
yl)-ethoxy]-naphthalen-1-yl}-urea;
1-[5-tert-Butyl-2-(2-hydroxy-4-methyl-phenyl)-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
4-(3-tert-Butyl-5-{3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-
ureido}-pyrazol-1-yl)-benzoic acid;
1-[5-(1,1-Dimethyl-2-oxo-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-
morpholin-4-yl-ethoxy)-naphthalen-1-yl]-urea;
2-Methyl-2-(5-{3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-ureido}-
1-p-tolyl-1H-pyrazol-3-yl)-propionic acid;
1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-2-oxo-
ethoxy)-naphthalen-1-yl]-urea and
1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{4-[2-(1-oxo-1λ 4 -
thiomorpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea
or physiologically acceptable acids or salts thereof.Join the waitlist — get patent alerts
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