Patent ES-8401474-A1 (ES)
Title: N-Phenalkyl:aminoalkyl-3-benzazepine derivs.
IPC: C07D223/16
Filed: 1982-11-29
Abstract: EP--65229 A Benzazepine derivs. of formula (I) and their addition salts are new: (A is CH2CH2, CH:CH, NHCO, CH2CO or CR7:N (NH, CH2 or CR7 being at 5 position), and B is then methylene or carbonyl, or A is COCO and B is then methylene. E is ethylene, n-propylene, or n-butylene, opt. substd. by a 1-3C alkyl or is 2-hydroxy substd. n-propylene or 2- or 3-hydroxy substd. n-butylene G is methylene or ethylene opt. substd. by a 1-3C alkyl. R1 and R2 are hydroxy, 1-3C alkyl or alkoxy, phenyl (1-3C)alkoxy, one of them can also be H, or R1 and R2 are together 1-2C alkylenedioxy. R3 and R4 are H, halo, hydroxy, 1-4C alkyl or alkoxy, trifluoro methyl or cyano, one of them can also be nitro, or R3 and R4 are together 1-2C alkylenedioxy. R5 is H, alkyl, hydroxy, alkoxy, amino (opt. substd. by 1 or 2 alkyl, by one alkanoyl, or by 1 or 2 alkoxycarbonyl) all alkyl having 1-3C, or is a methylamino or ethylamino gp. substd. by trifluoromethyl. R6 is H, alkyl, phenalkyl, alkanoyl or alkoxycarbonyl, (all alkyl 1-3C) or 3-5C alkenyl. R7 is 1-3C alkyl). They are made e.g. by reacting N-H benzazepines with Z.E.N(R6)G- substd. benzenes (Z is a leaving gp.). - (I) reduce the frequency and oxygen-demand of the heart, and have a long-lasting effect with reduced side effects (esp. low antimuscarinic effect), so are useful for treating sinus tachycardia and for preventing or treating ischaemic heart disorders. The only cpd. treated has intravenous and oral LD50's in mice 89-1350 mg per kg, respectively. EPAB- EP--65229 B Benzazepine derivs. of formula (I) and their addition salts are new: (A is CH2CH2, CH:CH, NHCO, CH2CO or CR7:N (NH, CH2 or CR7 being at 5 position), and B is then methylene or carbonyl, or A is COCO and B is then methylene. E is ethylene, n-propylene, or n-butylene, opt. substd. by a 1-3C alkyl or is 2-hydroxy substd. n-propylene or 2- or 3-hydroxy substd. n-butylene G is methylene or ethylene opt. substd. by a 1-3C alkyl. R1 and R2 are hydroxy, 1-3C alkyl or alkoxy, phenyl (1-3C)alkoxy, one of them can also be H, or R1 and R2 are together 1-2C alkylenedioxy. R3 and R4 are H, halo, hydroxy, 1-4C alkyl or alkoxy, trifluoro methyl or cyano, one of them can also be nitro, or R3 and R4 are together 1-2C alkylenedioxy. R5 is H, alkyl, hydroxy, alkoxy, amino (opt. substd. by 1 or 2 alkyl, by one alkanoyl, or by 1 or 2 alkoxycarbonyl) all alkyl having 1-3C, or is a methylamino or ethylamino gp. substd. by trifluoromethyl. R6 is H, alkyl, phenalkyl, alkanoyl or alkoxycarbonyl, (all alkyl 1-3C) or 3-5C alkenyl. R7 is 1-3C alkyl). They are made e.g. by reacting N-H benzazepines with Z.E.N(R6)G- substd. benzenes (Z is a leaving gp.). - (I) reduce the frequency and oxygen-demand of the heart, and have a long-lasting effect with reduced side effects (esp. low antimuscarinic effect), so are useful for treating sinus tachycardia and for preventing or treating ischaemic heart disorders. The only cpd. treated has intravenous and oral LD50's in mice 89-1350 mg per kg, respectively. (135pp) - EP--65229 B Benzazepine derivatives of general formula (1) wherein A represents a -CH2-CH2-, -CH=CH-, -NH-CO-, -CH2-CO- or -CR7=N-group wherein R7 represents an alkyl group containing 1 to 3 carbon atoms, and B represents a methylene or carbonyl group or A represents a -CO-CO group and B represents a methylene group. E represents an ethylene, n-propylene or n-butylene group optionally substituted by an alkyl group containing 1 to 3 carbon atoms,   an n-propylene group substituted by a hydroxy group in the 2 position or an n-butylene group substituted by a hydroxy group in the 2 or 3 position, G represents a methylene or ethylene group optionally substituted by an alkyl group with 1 to 3 catbon atoms, R1 and R2, which may be the same or different, represent hydroxy groups, alkyl, alkoxy or phenylalkoxy groups wherein the alkyl part may contain 1 to 3 carbon atoms, or one of the groups R1 or R2 may also represent a hydrogen atom or R1 together with R2 may represent an alkylenedioxy group with 1 or 2 carbon atoms, R3 and R4, which may be the same or different, represent hydrogen or halogen atoms, hydroxy groups, alkyl or alkoxy groups each having 1 to 4 carbon atoms, trifluoromethyl or cyano groups or one of the groups R3 or R4 may also represent a nitro group or R3 together with R4 may represent an alkylenedioxy group with 1 or 2 carbon atoms, R5 represents a hydrogen atom, an alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino or bis(alkoxycarbonyl)amino group wherein the alkyl part may contain 1 to 3 carbon atoms, or a methylamino or ethylamino group substituted by a trifluoromethyl group, and R6 represents a hydrogen atom, an alkyl, phenylalkyl, alkanoyl or alkoxycarbonyl group wherein the alkyl part may contain from 1 to 3 carbon atoms, or an alkenyl group with 3 to 5 carbon atoms, and the addition salts thereof, particularly the physiologically acceptable acid addition salts thereof with inorganic or organic acids.  (81pp) GBAB- GB2099425 B Compounds of general formula (I) (wherein A represents a group of formula -CH2-CH2-, -CH=CH-, -NH-CO-, -CH2-CO- or CR7-N- (wherein R7 represents an alkyl group containing 1 to 3 carbon atoms) and B represents a methylene or carbonyl group, or A represents a -CO-CO- group and B represents a methylene group; E represents an ethylene, n-propylene or n-butylene group (optionally substituted by an alkyl group containing 1 to 3 carbon atoms), an n-propylene group substituted at the 2-position by a hydroxy group or n-butylene group substituted at the 2- or 3-position by a hydroxy group; G represents a methylene or ethylene group (optionally substituted by an alkyl group containing 1 to 3 carbon atoms); R1 and R2, which may be the same or different, each represents a hydroxy group, an alkyl group containing 1 to 3 carbon atoms, or an alkoxy or phenylalkoxy group (in each of which the alkyl part may contain 1 to 3 carbon atoms) or one of the radicals R1 and R2 represents a hydrogen atom or R1 together with R2 represents an alkylenedioxy group containing 1 or 2 carbon atoms; R3 and R4 which may be the same or different, each represents a hydrogen or halogen atom, a hydroxy group, an alkyl or alkoxy group, each of which may contain 1 to 4 carbon atoms, or a trifluoromethyl or cyano group or one of the radicals R3 or R4 represents a nitro group or R3 together with R4 represents an alkylenedioxy group containing 1 or 2 carbon atoms; R5 represents a hydrogen atom, a hydroxy or amino group, an alkyl, alkoxy or alkylamino group containing 1 to 3 carbon atoms or a dialkylamino, alkanoylamino, alkoxycarbonylamino or bis(alkoxycarbonyl)amino group, in each of which the alkyl part may contain from 1 to 3 carbon atoms, or a methylamino or ethylamino group substituted by a trifluoromethyl group; and R6 represents a hydrogen atom, an alkyl group containing from 1 to 3 carbon atoms, or a phenylalkyl, alkanoyl or alkoxycarbonyl group, in each of which the alkyl part may contain from 1 to 3l - GB2099425 B Compounds of general formula (I) (wherein A represents a group of formula -CH2-CH2-, -CH =CH-, -NH-CO-, -CH2-CO- or CR7-N- (wherein R7 represents an alkyl group containing 1 to 3 carbon atoms) and B represents a methylene or carbonyl group, or A represents a -CO-CO- group and B represents a methylene group; E represents an ethylene, n-propylene or n-butylene group (optionally substituted by an alkyl group containing 1 to 3 carbon atoms), an n-propylene group substituted at the 2-position by a hydroxy group or n-butylene group substituted at the 2- or 3-position by a hydroxy group; G represents a methylene or ethylene group (optionally substituted by an alkyl group containing 1 to 3 carbon atoms); R1 and R2, which may be the same or different, each represents a hydroxy group, an alkyl group containing 1 to 3 carbon atoms, or an alkoxy or phenylalkoxy group (in each of which the alkyl part may contain 1 to 3 carbon atoms) or one of the radicals R1 and R2 represents a hydrogen atom or R1 together with R2 represents an alkylenedioxy group containing 1 or 2 carbon atoms; R3 and R4 which may be the same or different, each represents a hydrogen or halogen atom, a hydroxy group, an alkyl or alkoxy group, each of which may contain 1 to 4 carbon atoms, or a trifluoromethyl or cyano group or one of the radicals R3 or R4 represents a nitro group or R3 together with R4 represents an alkylenedioxy group containing 1 or 2 carbon atoms; R5 represents a hydrogen atom, a hydroxy or amino group, an alkyl, alkoxy or alkylamino group containing 1 to 3 carbon atoms or a dialkylamino, alkanoylamino, alkoxycarbonylamino or bis(alkoxycarbonyl)amino group, in each of which the alkyl part may contain from 1 to 3 carbon atoms, or a methylamino or ethylamino group substituted by a trifluoromethyl group; and R6 represents a hydrogen atom, an alkyl group containing from 1 to 3 carbon atoms, or a phenylalkyl, alkanoyl or alkoxycarbonyl group, in each of which the alkyl part may contain from 1 to 3