Patent EP-0199845-B1 (EP)
IPC: C07D409/12
Filed: 1985-11-07
Granted: 1990-08-01
Abstract: 1. Claims for the Contracting States : DE FR GB BE NL LU IT SE CH LI Imidazolyl alkyl guanidine derivatives corresponding to the general formula I   see diagramm : EP0199845,P73,F1   in which R denotes the group :   see diagramm : EP0199845,P73,F2   wherein R**1 and R**2 , which may be identical or different, denote hydrogen, straight chain C1 -C3 alkyl or C5 -C6 cycloalkyl or R**1 and R**2 together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or homopiperidine ring, R**3 stands for a hydrogen atom, a halogen atom or a C1 -C3 alkoxy group, A stands for the group -O-(CH2 )k -, -O-CH2 CH(OH)CH2 -, -O-CH2 CH(CH3 )-CH2 -, -CH2 -O-CH2 -CH(OH)-CH2 or -O-CH2 -CH(OH)-CH(OH)-CH2 wherein k has the value 3 or 4 or in which R denotes the group   see diagramm : EP0199845,P73,F3   or   see diagramm : EP0199845,P73,F4   wherein R**4 stands for a hydrogen atom, a halogen atom preferably attached in the para position to A, a C1 -C3 alkoxy group or a C1 -C3 alkyl group and A has the meaning indicated above, or in which R denotes the group :   see diagramm : EP0199845,P73,F5   wherein R**5 and R**6 , which may be identical or different, stand for a hydrogen atom, a halogen atom or a straight chain C1 -C3 alkyl group or a straight chain C1 -C3 alkoxy group, B may be attached in position 2, 3 or 4 of the pyridine ring and denotes the group   see diagramm : EP0199845,P73,F6   wherein 1 has the value 2, 3 or 4 and Y stands for a hydrogen atom or for a straight chain C1 -C3 alkyl group, or in which R denotes the group R"-A'-B' wherein R" stands for a phenyl or naphthyl group which may be unsubstituted or substituted with a halogen atom, with a C1 -C3 alkyl group or with a C1 -C3 alkoxy group. A' stands for a single bond or for the group -CR'**1 R'**2 or for a nitrogen atom substituted with an optionally halogen-substituted phenyl or benzyl group or with a straight chain C1 -C3 alkyl group, R'**1 denoting a hydrogen atom or a methyl group. R'**2 stands for a phenyl or pyridyl group optionally substituted with a halogen atom or with a C1 -C3 alkyl group. B' stands for the following groups : -CH(Y)-S-(CH2 )m' -, -CH2 -S-CH2 -CH(Y)-CH2 -, -CH2 -S-CH(Y)-CH2 -, -CH2 -S-CH2 -CH(Y)-, -(CH2 )n" -, -CH2 -CH(Y)-, -(CH2 )n" -CH(Y)-, -O-(CH2 )2 -, -CH2 -O-(CH2 )o' -, -CH2 -O-CH2 -CH(Y)-CH2 -, -O-CH2 -CH(Y)-, -O-CH(Y)-CH2 -, -S-(CH2 )q -, -S-CH2 -CH(Y)-, -S-CH(Y)-CH2 - or -S-CH2 -CH(Y)-CH2 wherein Y denotes a hydrogen atom or a straight chain C1 -C3 alkyl group, m' and o' have the value 2 or 3 and n" and q have the value 2, 3, 4 or 5, or in which R denotes the group R'"-A"-B"- wherein R'" stands for a pyridyl, thiophenyl, furanyl, quinolyl or benzimidazolyl group, which groups may be unsubstituted or substituted with halogen atoms, with C1 -C3 alkyl groups or with the group R**1 R**2 N-CH2 -, A" stands for a single bond or for the group -CR'**1 R'**2 or for a nitrogen atom substituted with a phenyl or benzyl group which is optionally substituted with halogen atoms, with C1 -C3 alkyl groups or with C1 -C3 alkoxy groups, R'**1 denoting a hydrogen atom or a methyl group and R'**2 denoting a phenyl or thiophenyl group optionally substituted with halogen atoms, under the condition that A" does not stand for a single bond when R'" is a pyridyl group. B" stands for the group -CH(Y)-S-(CH2 )m' -, -CH2 -S-CH2 -CH(Y)-CH2 -, -CH2 -S-CH(Y)-CH2 -, -(CH2 )n" -CH(Y)-, -CH2 -S-CH2 -CH(Y)-, -(CH2 )n" -, -O(CH2 )n" -, -S-CH2 -CH(Y)-, -S-CH(Y)-CH2 -, -S-(CH2 )q - or -S-CH2 -CH(Y)-CH2 - wherein Y denotes a hydrogen atom or a straight chain C1 -C3 alkyl group, m' has the value 2 or 3 and n" and q have the value 2, 3, 4 or 5, X denotes a hydrogen atom or a benzoyl group, p has the value 2 or 3 and R' denotes a hydrogen atom or a methyl group, and the physiologically acceptable salts thereof. 1. Claims for the Contracting State : AT Process for the preparation of imidazolyl alkyl guanidine derivatives corresponding to the general formula I   see diagramm : EP0199845,P77,F2   in which R denotes the group   see diagramm : EP0199845,P77,F3   wherein R**1 and R**2 , which may be identical or different, denote hydrogen, straight chain C1 -C3 alkyl or C5 -C6 cycloalkyl or R**1 and R**2 together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or homopiperidine ring, R**3 stands for a hydrogen atom, a halogen atom or a C1 -C3 alkoxy group, A denotes the group -O-(CH2 )k -, -O-CH2 CH(OH)CH2 -, -O-CH2 CH(CH3 )-CH2 -, -CH2 -O-CH2 -CH(OH)-CH2 or -O-CH2 -CH(OH)-CH(OH)-CH2 wherein k has the value 3 or 4 or in which R denotes the group   see diagramm : EP0199845,P77,F4   or   see diagramm : EP0199845,P77,F5   wherein R**4 stands for a hydrogen atom, a halogen atom preferably attached in the para position to A, a C1 -C3 alkoxy group or a C1 -C3 alkyl group and A has the meaning indicated above, or in which R denotes the group :   see diagramm : EP0199845,P77,F6   wherein R**5 and R**6 , which may be identical or different, stand for a hydrogen atom, a halogen atom or a straight chain C1 -C3 alkyl group or a straight chain C1 -C3 alkoxy group, B may be attached in position 2, 3 or 4 of the pyridine ring and denotes the group   see diagramm : EP0199845,P78,F1   wherein 1 has the value 2, 3 or 4 and Y stands for a hydrogen atom or for a straight chain C1 -C3 alkyl group, or in which R denotes the group R"-A'-B' wherein R" stands for a phenyl or naphthyl group which may be unsubstituted or substituted with a halogen atom, a C1 -C3 alkyl group or a C1 -C3 alkoxy group. A' stands for a single bond or for the group -CR'**1 R'**2 or for a nitrogen atom substituted with an optionally halogen-substituted phenyl or benzyl group or straight chain C1 -C3 alkyl group, R'**1 denoting a hydrogen atom or a methyl group. R'**2 stands for a phenyl or pyridyl group optionally substituted with a halogen atom or with a C1 -C3 alkyl group. B' stands for the groups : -CH(Y)-S-(CH2 )m' -, -CH2 -S-CH2 -CH(Y)-CH2 -, -CH2 -S-CH(Y)-CH2 -, -CH2 -S-CH2 -CH(Y)-, -(CH2 )n" -, -CH2 -CH(Y)-, -(CH2 )n" -CH(Y)-, -O-(CH2 )2 -, -CH2 -O-(CH2 )o' -, -CH2 -O-CH2 -CH(Y)-CH2 -, -O-CH2 -CH(Y)-, -O-CH(Y)-CH2 -, -S-(CH2 )q -, -S-CH2 -CH(Y)-, -S-CH(Y)-CH2 - or -S-CH2 -CH(Y)-CH2 wherein Y denotes a hydrogen atom or a straight chain C1 -C3 alkyl group, m' and o' have the value 2 or 3 and n" and q have the value 2, 3, 4 or 5, or in which R denotes the group R'"-A"-B"- wherein R'" stands for a pyridyl, thiophenyl, furanyl, quinolyl or benzimidazolyl group, which may be unsubstituted or substituted with halogen atoms, with C1 -C3 alkyl groups or with the group R**1 R**2 N-CH2 -, A" stands for a single bond or for the group -CR'**1 R'**2 or for a nitrogen atom substituted with a phenyl or benzyl group, which phenyl or benzyl group is optionally substituted with halogen atoms, with C1 -C3 alkyl groups or with C1 -C3 alkoxy groups, R'**1 denotes a hydrogen atom or a methyl group and R'**2 denotes an optionally halogen-substituted phenyl or thiophenyl group, under the condition that A" does not stand for a single bond when R'" is a pyridyl group. B" stands for the group -CH(Y)-S-(CH2 )m' -, -CH2 -S-CH2 -CH(Y)-CH2 -, -CH2 -S-CH(Y)-CH2 -, -(CH2 )n" -CH(Y)-, -CH2 -S-CH2 -CH(Y)-, -(CH2 )n" -, -O(CH2 )n" -, -S-CH2 -CH(Y)-, -S-CH(Y)-CH2 -, -S-(CH2 )q - or -S-CH2 -CH(Y)-CH2 - wherein Y denotes a hydrogen atom or a straight chain C1 -C3 alkyl group, m' has the value 2 or 3 and n" and q have the value 2, 3, 4 or 5, X denotes a hydrogen atom or a benzoyl group, p has the value 2 or 3 and R' denotes a hydrogen atom or a methyl group, and the physiologically acceptable salts thereof, characterised in that a) for the preparation of compounds corresponding to the general formula I in which R, A, B, p and R' are defined as above and X stands for a benzoyl group, (a1 ) a compound corresponding to the general formula II   see diagramm : EP0199845,P78,F2   in which R has the meaning indicated above is reacted with a compound corresponding to the general formula III   see diagramm : EP0199845,P79,F1   wherein R' and p have the meanings indicated above to form a compound corresponding to the general formula I or (a2 ) a compound corresponding to the general formula IV   see diagramm : EP0199845,P79,F2   wherein R' and p have the meanings indicated above is reacted with a compound corresponding to the general formula V R-NH2 in which R has the meaning indicated above to form a compound corresponding to the general formula I or b) for the preparation of compounds corresponding to the general formula I in which R, A, B, p and R' are defined as above and X stands for a hydrogen atom, (b1 ) a compound corresponding to formula Ia   see diagramm : EP0199845,P79,F3   wherein R, p and R' have the meanings indicated above is hydrolysed or (b2 ) a compound corresponding to the general formula VI   see diagramm : EP0199845,P79,F4   wherein R, p and R' have the meanings indicated above is hydrolysed by means of an acid to form a compound corresponding to the general formula I or (b3 ) a compound corresponding to the general formula VII   see diagramm : EP0199845,P79,F5   wherein R has the meaning indicated above is reacted with a compound corresponding to the above indicated general formula III wherein R' and p have the meanings indicated above to form a compound corresponding to the general formula I, or (b4 ) a compound corresponding to the general formula VIII   see diagramm : EP0199845,P80,F1   wherein R' and p have the meanings indicated above is reacted with a compound corresponding to the above indicated general formula V in which R has the meaning indicated above to form a compound corresponding to the general formula I and in that the compounds obtained under a) and b) are optionally converted into their physiologically acceptable salt.