Patent EA-003553-B1 (EA)
Title: Pyrimidin-aminomethyl-pyridine derivatives, their preparation and their use in the control of helicobacter bacteria
Inventor: HANAUER GUIDO
IPC: A61P31/04
Filed: 1999-05-20
Abstract: 1. A compound of the formula I in which R1, R2 and R3 are identical to or different from one another and are hydrogen, C1-C4alkyl or halogen, R4 is hydrogen or C1-C4alkyl, R5 is hydrogen or C1-C4alkyl, R6 is hydrogen or C1-C4alkyl, R7 is hydrogen, C1-C4alkyl, C1-C4alkoxy or halogen, R8 is hydrogen, C1-C4alkyl, C1-C4alkoxy or halogen, R9 is hydrogen or C1-C4alkyl, A is C1-C7alkylene, C2-C7alkenylene, C3-C7cycloalkylene or phenylene, G is hydrogen, hydroxyl, C1-C7alkyl, C1-C4alkyl which is completely or mainly substituted by fluorine, C2-C7alkenyl, C3-C7cycloalkyl, a mono- or di- C1-C4alkylcarbamoyl or -thiocarbamoyl group, an N- C1-C4alkyl-N'-cyanoamidino group, a 1-N- C1-C4alkylamino-2-nitroethylene group, an N-2-propynyl-N'-cyanoamidino group, an aminosulfonylamidino group, the group (R10)R11, the part of the compound of the above formula I bonded to A (including X and via X), the glucopyranoside group or a cyclic system or bicyclic system which is unsubstituted or substituted by R12 and R13 and which is selected from the group consisting of benzene, naphthalene, furan, thiophene, pyrrole, oxazole, oxazoline, oxazolidinone, isoxazole, thiazole, thiazoline, isothiazole, imidazole, imidazoline, pyrazole, triazole, tetrazole, thiadiazole, thiodiazole 1-oxide, oxadiazole, pyridine, pyridine N-oxide, pyrimidine, halopyrimidine, piperidine, triazine, pyridone, benzimidazole, imidazopyridine, benzothiazole, benzoxazole, quinoline and imidazopyridazine, in which R10 is C3-C7alkyl, C3-C7cycloalkyl or Ar- C1-C4alkyl and R11 is C1-C7-alkyl, C3-C7-cycloalkyl or Ar- C1-C4alkyl, Where Ar is phenyl, furyl, naphthyl, tetrahydronaphthyl or phenyl which is substituted by R14, R15 and R16, or in which R10 and R11, together and including the nitrogen atom to which both are bonded, are an unsubstituted or substituted 5- or 6-membered ring hetero(bi)cyclic system which is selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, indoline, 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline, where a substituted pyrrolidino group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxy, C1-C4alkoxy- C1-C4alkyl, C1-C4alkoxycarbonyl, C1-C4alkylcarbonyloxy, hydroxy- C1-C4alkyl, hydroxyl and carboxyl, a substituted piperidino group is substituted by one, two or three identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxycarbonyl, hydroxy- C1-C4alkyl, phenyl or phenyl- C1-C4alkyl, which is substituted by R14, R15 and R16, benzoyl, benzoyl substituted by halogen and carboxyl, a substituted piperazino group can be substituted in the 2-, 3-, 5- or 6-position by a C1-C4alkyl group, and is substituted in the 4-position by a substituent selected from the group consisting of C1-C4alkyl, C3-C7-cycloalkyl, C3-C7cycloalkyl- C1-C4alkyl, C1-C4alkoxycarbonyl- C1-C4alkyl and carbamoyl, a substituted morpholino group is substituted by one or two identical or different C1-C4alkyl groups, a substituted thiomorpholino group is substituted by one or two identical or different C1-C4alkyl groups or a carboxyl group, a substituted indolin-1-yl group can be substituted in the 2- and/or 3-position by a carboxyl group or by one or two identical or different C1-C4alkyl groups, and can be substituted in the benzo moiety by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, halogen and nitro, a substituted 1,2,3,4-tetrahydroquinoline group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxycarbonyl and halogen, a substituted 1,2,3,4-tetrahydroisoquinoline group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, carboxyl and phenyl, R12 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen, nitro, guanidino, carboxyl, C1-C4alkoxycarbonyl, C1-C4alkyl substituted by R17, phenyl substituted by R14, R15 and R16 or -N(R18)R19, R13 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen or trifluoromethyl, R14 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, C1-C4alkylcarbonyl, halogen, trifluoromethyl, C1-C4alkylamino or nitro, R15 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen or nitro, and R16 is hydrogen or trifluoromethyl, R17 is hydroxyl, C1-C4alkoxy, carboxyl, C1-C4alkoxycarbonyl, pyridinyl or -N(R18)R19, where R18 is hydrogen, C1-C4alkyl or -CO-R20 and R19 is hydrogen or C1-C4alkyl, or where R18 and R19, together and including the nitrogen atom to which both are bonded, are a piperidino or morpholino group, R20 is hydrogen, C1-C4alkyl or C1-C4alkoxy, X is O (oxygen), N- C1-C4alkyl, NH or S, Y is O (oxygen), N- C1-C4alkyl, NH, S, 1,4-piperazinylene or 1,4-piperidinylene, Z is O (oxygen), N- C1-C4alkyl, NH or S or CO, m is a number from 1 to 7, n is a number from 0 to 4, t is the number 0, 1 or 2 and u is the number 0 or 1, or its salts. 2. A compound of the formula I as claimed in claim 1, in which R1, R2 and R3 are identical to or different from one another and are hydrogen, C1-C4alkyl or halogen, R4 is hydrogen or C1-C4alkyl, R5 is hydrogen or C1-C4alkyl, R6 is hydrogen or C1-C4alkyl, R7 is hydrogen, C1-C4alkyl, C1-C4alkoxy or halogen, R8 is hydrogen, C1-C4alkyl, C1-C4alkoxy or halogen, R9 is hydrogen or C1-C4alkyl, A is C1-C7alkylene, C2-C7alkenylene, C3-C7cycloalkylene or phenylene, G is hydrogen, C1-C7alkyl, C1-C4alkyl which is completely or mainly substituted by fluorine, C2-C7alkenyl, C3-C7cycloalkyl, a mono- or di- C1-C4alkylcarbamoyl or -thiocarbamoyl group, an N- C1-C4alkyl-N'-cyanoamidino group, a 1-N- C1-C4alkylamino-2-nitroethylene group, an N-2-propynyl-N'-cyanoamidino group, an aminosulfonylamidino group, the group -N(R10)R11, or a cyclic system or bicyclic system which is unsubstituted or substituted by R12 and R13 and which is selected from the group consisting of benzene, naphthalene, furan, thiophene, pyrrole, oxazole, oxazoline, isoxazole, thiazole, thiazoline, isothiazole, imidazole, imidazoline, pyrazole, triazole, tetrazole, thiadiazole, thiodiazole 1-oxide, oxadiazole, pyridine, pyridine N-oxide, pyrimidine, halopyrimidine, piperidine, triazine, pyridone, benzimidazole, imidazopyridine, benzothiazole, benzoxazole, quinoline and imidazopyridazine, in which R10 is or Ar- C1-C4alkyl and R11 is C1-C7alkyl, C3-C7cycloalkyl or Ar- C1-C4alkyl, where Ar is phenyl, furyl, naphthyl, tetrahydronaphthyl or phenyl which is substituted by R14, R15 and R16, or in which R10 and R11, together and including the nitrogen atom to which both are bonded, are an unsubstituted or substituted 5- or 6-membered ring hetero(bi)cyclic system which is selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, indoline, 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline, where a substituted pyrrolidino group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxy, C1-C4alkoxy- C1-C4alkyl, C1-C4alkoxycarbonyl, C1-C4alkylcarbonyloxy, hydroxy- C1-C4alkyl, hydroxyl and carboxyl, a substituted piperidino group is substituted by one, two or three identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxycarbonyl, hydroxy- C1-C4alkyl, phenyl or phenyl- C1-C4alkyl, which is substituted by R14, R15 and R16, benzoyl, benzoyl substituted by halogen and carboxyl, a substituted piperazino group can be substituted in the 2-, 3-, 5- or 6-position by a C1-C4alkyl group, and is substituted in the 4-position by a substituent selected from the group consisting of C1-C4alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl- C1-C4alkyl, C1-C4alkoxycarbonyl- C1-C4alkyl and carbamoyl, a substituted morpholino group is substituted by one or two identical or different C1-C4alkyl groups, a substituted thiomorpholino group is substituted by one or two identical or different C1-C4alkyl groups or a carboxyl group, a substituted indolin-1-yl group can be substituted in the 2- and/or 3-position by a carboxyl group or by one or two identical or different C1-C4alkyl groups, and can be substituted in the benzo moiety by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, halogen and nitro, a substituted 1,2,3,1-tetrahydroquinoline group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, C1-C4alkoxycarbonyl and halogen, a substituted 1,2,3,4-tetrahydroisoquinoline group is substituted by one or two identical or different substituents selected from the group consisting of C1-C4alkyl, carboxyl and phenyl, R12 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen, nitro, guanidino, carboxyl, C1-C4alkoxycarbonyl, C1-C4alkyl substituted by R17, phenyl substituted by R14, R15 and R16 or -N(R18)R19, R13 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen or trifluoromethyl, R14 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, C1-C4alkylcarbonyl, halogen, trifluoromethyl, C1-C4alkylamino or nitro, R15 is hydrogen, C1-C4alkyl, hydroxyl, C1-C4alkoxy, halogen or nitro, and R16 is hydrogen or trifluoromethyl, R17 is hydroxyl, C1-C4alkoxy, carboxyl, C1-C4alkoxycarbonyl or -N (R18) R19, where R18 is hydrogen, C1-C4alkyl or -CO-R20 and R19 is hydrogen or C1-C4alkyl, or where R18 and R19, together and including the nitrogen atom to which both are bonded, are a piperidino or morpholino group, R20 is hydrogen, C1-C4alkyl or C1-C4alkoxy, X is O (oxygen), N- C1-C4alkyl, NH or S, Y is O (oxygen), N- C1-C4alkyl, NH, S, 1,4-piperazinylene or 1,4-piperidinylene, Z is O (oxygen), N- C1-C4alkyl, NH or S or CO, m is a number from 1 to 7, n is a number from 0 to 4, t is the number 0 or 1 and u is the number 0 or 1, or its salts. 3. A compound of the formula I as claimed in claim 1, in which R1 is hydrogen or C1-C4