Patent EA-002764-B1 (EA)
Title: Phthalazinones
IPC: A61P11/06
Filed: 1998-01-12
Abstract: 1. A compound of formula    in which R1 is 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R2 is 1-8C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R3 and R4 are both hydrogen or together form an additional bond, R5 is R6, -CmH2m-R7, -Cn H2n-C(O)R8, -CH(R9)2 -Cp H2p-Ar, in which R6 is hydrogen (H), 1-8C-alkyl, 3-10C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, 7-10C-polycycloalkyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, indanyl, benzoxazolyl, benzothiazolyl, oxazolyl, thiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiapyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which R61 is 1-4C-alkyl, 1-4C-alkoxy, nitro, halogen, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, 4-methylphenylsulfonamido, tetrazol-5-yl, 2-(1-4C-alkyl)tetrazol-5-yl or 2-benzyl-tetrazol-5-yl and R62 is 1-4C-alkyl, 1-4C-alkoxy, nitro or halogen, R7 is hydroxyl, halogen, cyano, nitro, nitroxy(-O-NO2), carboxyl, carboxyphenyloxy, phenoxy, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl, pyrrolidinyl or morpholinyl radical, where R71 is hydroxyl, 1-4C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxycarbonyl, and R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl, R8 is an unsubstituted or by R81 and/or R82 substituted phenyl, naphthyl, phenanthrenyl or anthracenyl radical, in which R81 is hydroxyl, halogen, cyano, 1-4C-alkyl, 1-4C-alkoxy, carboxyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, and R82 is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R9 is -Cq H2q -phenyl, Ar is an unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, a 2-(1-4C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which R10 is hydroxyl, halogen, nitro, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-4-4-C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkyl-amino, 1-4-C-alkylcarbonylamino, aminocarbonyl or mono- or di-1-4C-alkylamino-carbonyl, and R11 is hydroxyl, halogen, nitro, 1-4C-alkyl or 1-4C-alkoxy, m is an integer from 1 to 8, n is an integer from 1 to 4, p is an integer from 1 to 6, q is an integer from 0 to 2, or a salt thereof. 2. A compound of formula I according to Claim 1, in which R1 is 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R2 is 1-8C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R3 and R4 are both hydrogen or together form an additional bond, R5 is R6, -CmH2m-R7, -Cn H2n-C(O)R8, -CH(R9)2 -Cp H2p -Ar, in which R6 is hydrogen (H), 1-8C-alkyl, 3-10C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, bornyl, norbornyl, adamantyl or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which R61 is 1-4-C-alkyl, 1-4C-alkoxy, nitro or halogen, and R62 is 1-4C-alkyl, nitro or halogen, R7 is hydroxyl, halogen, cyano, nitro, carboxyl, phenoxy, 1-4-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl, pyrrolidinyl or morpholinyl radical, where R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl, R8 is an unsubstituted or by R81 and/or R82 substituted phenyl, naphthyl, phenanthrenyl or anthracenyl radical, in which R81 is hydroxyl, halogen, cyano, 1-4C-alkyl, 1-4C-alkoxy, carboxyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, and R82 is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R9 is -CqH2q-phenyl, Ar is an unsubstituted phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, quinazolinyl, quinoxalinyl, cinnolinyl, isoquinolyl, quinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, furyl, thienyl, pyrrolyl, a 2-(1-4C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which R10 is hydroxyl, halogen, nitro, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, aminocarbonyl or mono- or di-1-4C-alkylaminocarbonyl, and R11 is hydroxyl, halogen, nitro, 1-4C-alkyl or 1-4C-alkoxy, m is an integer from 1 to 8, n is an integer from 1 to 4, p is an integer from 1 to 4, q is an integer from 0 to 2, or a salt thereof. 3. A compound of formula I according to Claim 1, in which R1 is 1-4C-alkoxy or 1-2C-alkoxy which is completely or predominantly substituted by fluorine, R2 is 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-2C-alkoxy which is completely or predominantly substituted by fluorine, R3 and R4 are both hydrogen or together form an additional bond, R5 is R6, -CmH2m-R7, -CnH2n-C(O)R8, -CH(R9)2 or -CpH2p-Ar, in which R6 is hydrogen, 1-8C-alkyl, 3-8C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-7C-alkenyl, 3-7C-alkynyl, phenyl-3-4C-alkenyl, bornyl, norbornyl, adamantyl, naphthyl, pyridyl, quinoxalinyl, indanyl, benzothiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which R61 is 1-2-C-alkyl, 1-2C-alkoxy, nitro, halogen, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, amino, mono- or di-1-4C-alkylamino, aminocarbonyl, aminosulfonyl, mono- or di-1-4C-alkylaminosulfonyl, 4-methylphenylsulfonamido, tetrazol-5-yl, 2-(1-4C-alkyl)tetrazol-5-yl or 2-benzyltetrazol-5-yl, and R62 is 1-2C-alkyl, 1-2C-alkoxy, nitro, or halogen, R7 is hydroxyl, halogen, carboxyl, nitroxy (-O-NO2), phenoxy, carboxyphenyloxy, 1-4C-alkoxy, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4-C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl or morpholinyl radical, where R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and R72 is 1-4-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl, R8 is an unsubstituted or by R81 and/or R82 substituted phenyl or naphthyl radical, where R81 is hydroxyl, halogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylcarbonyloxy, 1-4C-alkylcarbonylamino, or 1-2C-alkoxy which is completely or predominantly substituted by fluorine, and R82 is halogen, 1-4C-alkyl or 1-4C-alkoxy, R9 is -Cq H2q -phenyl, Ar is an unsubstituted phenyl, naphthyl, pyridyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, N-benzosuccinimidyl, imidazolyl, oxazolyl, thiazolyl, a 2-(1-2C-alkyl)-thiazol-4-yl radical, or a phenyl radical substituted by R10 and/or R11, in which R10 is hydroxyl, halogen, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, carboxyl, carboxy-1-4C-alkyl, 1-4C-alkylcarbonyloxy, 1-4C-alkoxycarbonyl and R11 is hydroxyl, halogen, 1-4C-alkyl or 1-4C-alkoxy, m is an integer from 1 to 8, n is an integer from 1 to 4, p is an integer from 1 to 6, q is an integer from 0 to 1, or a salt thereof. 4. A compound of formula I according to Claim 1 in which R1 is methoxy, ethoxy or difluoromethoxy, R2 is 1-4C-alkoxy, difluoromethoxy, 3-5C-cycloalkoxy or 3-5C-cycloalkylmethoxy, R3 and R4 are both hydrogen or together form an additional bond, R5 is R4, -Cm H2m -R7, -Cn H2n -C(O)R8, -CH(R9)2 or -Cp H2p -Ar, in which R6 is hydrogen, 1-8C-alkyl, 3-8C-cycloalkyl, 3-7C-cycloalkylmethyl, 3-4C-alkenyl, 3-4C-alkynyl, phenyl-3-4C-alkenyl, adamantyl, pyridyl, quinoxalinyl, indanyl, benzothiazolyl, N-methylpiperidyl, tetrahydropyranyl, tetrahydrothiopyranyl, or an unsubstituted or by R61 and/or R62 substituted phenyl radical, in which R61 is 1-2C-alkyl, 1-2C-alkoxy, nitro, halogen, carboxyl, carboxy-1-2C-alkyl, 1-4C-alkoxycarbonyl, hydroxy-1-2C-alkyl, amino, aminosulfonyl, 4-methylphenylsulfonamido, 2-(1-2C-alkyl)tetrazol-5-yl or 2-benzyltetrazol-5-yl, and R62 is 1-2C-alkyl or halogen, R7 is hydroxyl, halogen, carboxyl, nitroxy (-O-NO2), phenoxy, carboxyphenyloxy, 1-4C-alkoxycarbonyl, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, amino, mono- or di-1-4C-alkylamino, or an unsubstituted or by R71 and/or R72 substituted piperidyl, piperazinyl or morpholinyl radical, where R71 is hydroxyl, 1-4C-alkyl, 1-4C-hydroxyalkyl or 1-4C-alkoxycarbonyl, and R72 is 1-4C-alkyl, carboxyl, aminocarbonyl or 1-4C-alkoxycarbonyl, R8 is an unsubstituted or by R81 subst