Patent EA-005215-B1 (EA)
Title: Alkylated imidazopyridine derivatives
Inventor: SIMON WOLFGANG-ALEXANDER
IPC: A61K31/415
Filed: 2001-03-28
Abstract: 1. A compound of the formula 1 in which R1 is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy(C1-C4)-alkyl or hydroxy-(C1-C4)-alkyl, R2 is hydrogen, C1-C4-alkyl, hydroxy-(C1-C4)-alkyl, halogen, C2-C4-alkenyl or C2-C4-alkynyl, R3 is hydrogen, halogen, trifluoromethyl, C1-C4-alkyl, C2-C4-alkenyl or C2-C4-alkynyl, carbo, -CO-(C1-C4)-alkoxy, hydroxy-(C1-C4)-alkyl, C1-C4-alkoxy-(C1-C4)-alkyl, fluoro-(C1-C4)-alkoxy-(C1-C4)-alkyl or the radical-CO-NR3aR3b, one of the substituents R4a and R4b is hydrogen, C1-C7-alkyl, C2-C7-alkenyl, phenyl or phen(C1-C4)-alkyl and the other is hydroxyl, C1-C4-alkoxy, C1-C4-alkoxy-(C1-C4)-alkoxy, C1-C4-alkylcarbonyloxy or in which R4a and R4b together are O (oxygen C1-C7-alkylidene, one of the substituents R5a and R5b is hydrogen, C1-C7-alkyl, C2-C7-alkenyl, phenyl or phen(C1-C4)-alkyl and the other is hydrogen, hydroxyl, C1-C4-alkoxy, C1-C4-alkoxy-(C1-C4)-alkoxy, C1-C4 alkylcarbonyloxy or R5a and R5b together are O (oxygen); C1-C7-alkylidene, or one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, C1-C7-alkyl, C2-C7-alkenyl, phenyl or phen(C1-C4)alkyl, and the other substituents in each case together form a C1-C4-alkylenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning C1-C7-alkyl, C1-C7-alkenyl, phenyl or phen-(C1-C4)-alkyl or where either R4a and R4b or R5a and R5b together must be C1-C7-alkylidene, R6 is hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxycarbonylamino, C1-C4-alkoxy (C1-C4)-alkoxycarbonylamino or trifluoromethyl, R7 is hydrogen, halogen, C1-C4-alkyl or C1-C4-alkoxy and X is O (oxygen) or NH, where R3a is hydrogen, C1-C7-alkyl, hydroxy-(C1-C4)-alkyl or C1-C4-alkoxy-(C1-C4)-alkyl and R3b is hydrogen, C1-C7-alkyl, hydroxy-(C1-C4)-alkyl or C1-C4-alkoxy-(C1-C4)-alkyl, or where R3a and R3b together, including the nitrogen atom to which both are bonded, are pyrrolidino, piperidino or morpholino radical, or its salts. 2. A compound of the formula 1 as claimed in claim 1, in which R1 is C1-C4-alkyl, R2 is C1-C4-alkyl or hydroxy-(C1-C4)-alkyl, R3 is hydrogen, halogen, carboxyl, -CO-(C1-C4)-alkoxy, hydroxy-(C1-C4)-alkyl, C1-C4-alkoxy-(C1-C4) alkyl, fluoro-(C1-C4)-alkoxy-(C1-C4)-alkyl or the radical-CO-NR3aR3b, one of the substituents R4a and R4b is hydrogen, C1-C7-alkyl, C2-C7-alkenyl, phenyl or phen-(C1-C4)-alkyl and the other is hydroxyl, C1-C4-alkoxy, C1-C4-alkoxy-(C1-C4)-alkoxy or the radical -OR', or R4a and R4b together are O (oxygen) or C1-C4-alkylidene, or one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, C1-C7-alkyl, C2-C7-alkenyl, phenyl or phen(C1-C4)-alkyl, and the other substituents in each case together form a C1-C4-alkylenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning C1-C7 alkyl, C1-C7-alkenyl, phenyl or phen(C1-C4)-alkyl or where either R4a and R4b or R5a and R5b together must be C1-C4-alkylidene, R6 is hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxycarbonylamino, C1-C4-alkoxy(C1-C4)-alkoxycarbonylamino or trifluoromethyl, R7 is hydrogen, halogen, C1-C4-alkyl or C1-C4-alkoxy and X is O (oxygen) or NH, where R3a is hydrogen, C1-C7-alkyl, hydroxy(C1-C4)-alkyl or C1-C4-alkoxy-(C1-C4)-alkyl and R3b is hydrogen, C1-C7-alkyl, hydroxy(C1-C4)-alkyl or C1-C4-alkoxy-(C1-C4)-alkyl, or where R3a and R3b together, including the nitrogen atom to which both are bonded, are a pyrrolidino, piperidino or morpholino radical, and where R' is selected from the group consisting of -C(O)-NR8R9, -C(O)-alk-NR8R9, -C(O)-alk-C(O)-NR8R9, -P(O)(OH)2, -S(O)2NR8R9, -C(O)-R8, -C(O)-C6H3R9OR11, -C(O)-OR8, -C(O)-alk-C(O)-R8, -C(O)-alk-C(O)-OR8, -C(O)-C(O)-R8, -C(O)-C(O)-OR8 and -CH2-OR8, where alk is C1-C7-alkylene, R8 is hydrogen, C1-C10-alkyl or C1-C4-alkyl substituted by halogen, carboxyl, hydroxyl, sulfo (-SO3H), sulfamoyl(-SO2NH2), carbamoyl(-CONH2), C1-C4-alkoxy or C1-C4-alkoxycarbonyl, R9 is hydrogen or C1-C4-alkyl, R10 is hydrogen, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxycarbonyl, C1-C4 alkoxycarbonylamino, C1-C4-alkoxy-(C1-C4)-alkoxycarbonylamino or trifluoromethyl, and R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-alkoxy; or salts thereof. 3. A compound as claimed in claim 1, having the formula 1*, in which R1 is C1-C4-alkyl, R2 is C1-C4-alkyl, R3 is hydrogen, chlorine, fluorine, hydroxymethyl, difluoromethoxymethyl or the radical -CO-NR3aR3b, one of the substituents R4a and R4b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl, the other is hydroxyl, C1-C4-alkoxy, C1-C4-alkoxy(C1-C4)-alkoxy or the radical-OR', or R4a and R4b together are O (oxygen) or methylene, one of the substituents R5a and R5b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyls the other is hydroxyl, C1-C4-alkoxy, C1-C4-alkoxy(C1-C4)-alkoxy or the radical-OR', or R5a and R5b together are O (oxygen) or methylene, or in which one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand in each case is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyls the other substituents in each case together form a methylenedioxy, ethylenedioxy isopropylidenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl or where either R4a and R4b or R5a and R5b together must be methylene, R6 is hydrogen, R7 is hydrogen and X is O (oxygen) or NH, where R3a is hydrogen, C1-C4-alkyl, hydroxy(C1-C4)-alkyl or C1-C4-alkoxy(C1-C4)-alkyl and R3b is hydrogen, C1-C4-alkyl, hydroxy(C1-C4)-alkyl or C1-C4-alkoxy(C1-C4)-alkyl, and where R' is selected from the group consisting of -C(O)-NR8R9, -C(O)-alk-NR8R9, -C(O)-alk-C (O)-NR8R9, -P(O)(OH)2, -S(O)2NR8R9, -C(O)-R8, -C(O)-C6H3R10R11, -C(O)-OR8, -C(O)-alk-C(O)-OR8, -C(O)-C(O)-OR8 and -CH2-OR8, where alk is C1-C7-alkylene, R8 is hydrogen, C1-C10-alkyl, or C1-C4-alkyl, substituted by carboxyl or sulfo(-SO3H), R9 is hydrogen or C1-C4-alkyl, R10 is hydrogen, halogen, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxycarbonyl, C1-C4 alkoxycarbonylamino, C1-C4-alkoxy(C1-C4)-alkoxycarbonylamino or trifluoromethyl and R11 is hydrogen, halogen, C1-C4-alkyl or C1-C4-alkoxy; or salts thereof. 4. A compound as claimed in claim 1, which has the formula 1* as claimed in claim 3, in which R1 is methyl, R2 is methyl, R3 is hydrogen, chlorine, fluorine, hydroxymethyl, difluoromethoxymethyl or the radical-CO-NR3aR3b, one of the substituents R4a and R4b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl, the other is hydroxyl, C1-C4-alkoxy or C1-C4-alkoxy(C1-C4)-alkoxy, or R4a and R4b together are O (oxygen) or methylene, one of the substituents R5a and R5b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl the other is hydroxyl, or one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, C1-C4-alkyl, C2-C4-alkenyl, and the substituents in each case together are a methylenedioxy, ethylenedioxy isopropylidenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl or where R4a and R4b together must be methylen, R6 is hydrogen, R7 is hydrogen and X is O (oxygen) or NH, where R3a is hydrogen, methyl, ethyl, propyl, 2-hydroxyethyl or 2-methoxyethyl and R3b is hydrogen, methyl or ethyl, or salts thereof. 5. A compound as claimed in claim 1, which has the formula 1* as claimed in claim 3, in which R1 is methyl, R2 is methyl, R3 is hydrogen, chlorine, fluorine, hydroxymethyl, difluoromethoxymethyl or the radical-CO-NR3aR3b, one of the substituents R4a and R4b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl the other is hydroxyl, C1-C4-alkoxy or C1-C4-alkoxy(C1-C4)-alkoxy, or in which R4a and R4b together are O (oxygen) or methylene, R5a is C1-C4-alkyl, C2-C4-alkenyl, phenyl, benzyl or hydroxyl, R5b is hydrogen or hydroxyl, where R5a and R5b are not simultaneously hydroxyl, or one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, C1-C4-alkyl, C2-C4-alkenyl, and the substituents in each case together are a methylenedioxy, ethylenedioxy isopropylidenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl or where R4a and R4b together must be methylene R6 is hydrogen, R7 is hydrogen and X is O (oxygen) or NH, where R3a is hydrogen, methyl, ethyl, propyl, 2-hydroxyethyl or 2-methoxyethyl and R3b is hydrogen, methyl or ethyl, or salts thereof. 6. A compound as claimed in claim 1, which has the formula 1* as claimed in claim 3, in which R1 is methyl, R2 is methyl, R3 is hydrogen, one of the substituents R4a and R4b is hydrogen, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl, and the other is hydroxyl, C1-C4-alkoxy or C1-C4-alkoxy(C1-C4)-alkoxy, or in which R4a and R4b together are O (oxygen) or methylene, R5a is C1-C4-alkyl, C2-C4-alkenyl, phenyl, benzyl or hydroxyl, R5b is hydrogen or hydroxyl, where R5a and R5b are not simultaneously hydroxyl, or one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand is in each case hydrogen, C1-C4-alkyl, C2-C4-alkenyl, alkenyl, and the substituents in each case together are a methylenedioxy, ethylenedioxy isopropylidenedioxy radical, where at least one of the substituents R4a, R4b, R5a and R5b must have the meaning, C1-C4-alkyl, C2-C4-alkenyl, phenyl or benzyl or where R4a and R4b together must be methylene, R6 is hydrogen, R7 is hydrogen and X is O (oxygen) or NH, or salts thereof. 7. A medicament comprising a compound as claimed in claim 1 and/or a pharmacologically tolerable salt thereof together with customary pharmaceutical excipients