Pharmaceutical use of pyridine-2,4- and -2,5-dicarboxylic acid amides

A method for inhibiting proline hydroxylase and lysine hydroxylase in a mammal comprising administering a pharmaceutically effective amount of a pyridine-2,4- or -2,5-dicarboxylic acid diamide of the formula I' ##STR9## in which R.sup.1' denotes branched or unbranched C.sub.1 -C.sub.12 -alkyl which is optionally monosubstituted or, in the case of C.sub.2 -C.sub.12 -alkyl, optionally polysubstituted by halogen, hydroxyl, cyano, amino, carboxyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyl- or dialkylamino, wherein the alkyl radicals contain 1-4 carbon atoms, and the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched, or indolyl or phenyl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 -alkyl, the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched and in the case of polysubstitution, for the substituents to be the same or different, or

• R.sup.1' denotes saturated C.sub.5 -C.sub.7 -cycloalkyl, which is optionally benzo-fused, or
• R.sup.1' denotes aryl or heteroaryl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy, in the case of polysubstitution, the substituents being the same or different and in the case of the C.sub.3 - and C.sub.4 -alkyl radicals, the radicals being optionally branched, and
• R.sup.2', independently of R.sup.1', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.2' being optionally identical to R.sup.1',
• R.sup.3', independently of R.sup.1' and R.sup.2', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.3' being optionally identical to R.sup.1' or R.sup.2' or both, and
• R.sup.4', independently of R.sup.1', R.sup.2' and R.sup.3', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.4', being optionally identical to R.sup.1', R.sup.2', R.sup.3', or any combination thereof, and in which the radicals R.sup.1' and R.sup.2' or R.sup.3' and R.sup.4', or R.sup.1', R.sup.2', R.sup.3' and R.sup.4', together with the nitrogen atom, optionally forming a 5-, 6- or 7-membered saturated heterocyclic ring, the heterocyclic ring optionally including a second nitrogen atom and the heterocylic ring being optionally substituted by phenyl or phenyl-C.sub.1 -C.sub.3 -alkyl, or a physiologically tolerated salt thereof, excluding the compounds in which R.sup.1' is the same as R.sup.3', with R.sup.1' and R.sup.3' denoting phenyl which is disubstituted by methyl and bromine and R.sup.2' being the same as R.sup.4', with R.sup.2' and R.sup.4' denoting hydrogen.

A method for fibrosuppression and immunosuppression in a mammal comprising administering a pharmaceutically effective amount of a pyridine-2,4- or -2,5-dicarboxylic acid diamide of the formula I' ##STR10## in which R.sup.1' denotes branched or unbranched C.sub.1 -C.sub.12 -alkyl which is optionally monosubstituted or, in the case of C.sub.2 -C.sub.12 -alkyl, optionally polysubstituted by halogen, hydroxyl, cyano, amino, carboxyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyl- or dialkylamino, wherein the alkyl radicals contain 1-4 carbon atoms, and the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched, or indolyl or phenyl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 -alkyl, the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched and in the case of polysubstitution, for the substituents to be the same or different, or

• R.sup.1' denotes saturated C.sub.5 -C.sub.7 -cycloalkyl, which is optionally benzo-fused, or
• R.sup.1' denotes aryl or heteroaryl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy, in the case of polysubstitution, the substituents being the same or different and in the case of the C.sub.3 - and C.sub.4 -alkyl radicals, the radicals being optionally branched, and
• R.sup.2', independently of R.sup.1', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.2' being optionally identical to R.sup.1',
• R.sup.3', independently of R.sup.1' and R.sup.2', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.3' being optionally identical to R.sup.1' or R.sup.2' or both, and
• R.sup.4', independently of R.sup.1', R.sup.2' and R.sup.3', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.4', being optionally identical to R.sup.1', R.sup.2', R.sup.3', or any combination thereof, and in which the radicals R.sup.1' and R.sup.2' or R.sup.3' and R.sup.4', or R.sup.1', R.sup.2', R.sup.3' and R.sup.4', together with the nitrogen atom, optionally forming a 5-, 6- or 7-membered saturated heterocyclic ring, the heterocyclic ring optionally including a second nitrogen atom and the heterocyclic ring being optionally substituted by phenyl or phenyl-C.sub.1 -C.sub.3 -alkyl,
• or a physiologically tolerated salt thereof, excluding the compounds in which R.sup.1' is the same as R.sup.3', with R.sup.1' and R.sup.3' denoting phenyl which is disubstituted by methyl and bromine and R.sup.2' being the same as R.sup.4', with R.sup.2' and R.sup.4' denoting hydrogen.

A method for influencing the metabolism of collagen and collagen-like substances or the biosynthesis of Clq in a mammal comprising administering a pharmaceutically effective amount of a pyridine-2,4- or -2,5-dicarboxylic acid diamide of the formula I' ##STR11## in which R.sup.1' denotes branched or unbranched C.sub.1 -C.sub.12 -alkyl which is optionally monosubstituted or, in the case of C.sub.2 -C.sub.12 -alkyl, optionally polysubstituted by halogen, hydroxyl, cyano, amino, carboxyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyl- or dialkylamino, wherein the alkyl radicals contain 1-4 carbon atoms, and the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched, or indolyl or phenyl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 alkyl, the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched and in the case of polysubstitution, for the substituents to be the same or different, or

• R.sup.1' denotes saturated C.sub.5 -C.sub.7 -cycloalkyl, which is optionally benzo-fused, or
• R.sup.1' denotes aryl or heteroaryl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy, in the case of polysubstitution, the substituents being the same or different and in the case of the C.sub.3 - and C.sub.4 -alkyl radicals, the radicals being optionally branched, and
• R.sup.2', independently of R.sup.1', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.2' being optionally identical to R.sup.1',
• R.sup.3', independently of R.sup.1' and R.sup.2', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.3' being optionally identical to R.sup.1' or R.sup.2' or both, and
• R.sup.4', independently of R.sup.1', R.sup.2' and R.sup.3', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.4', being optionally identical to R.sup.1', R.sup.2', R.sup.3', or any combination thereof, and in which the radicals R.sup.1' and R.sup.2' or R.sup.3' and R.sup.4', or R.sup.1', R.sup.2', R.sup.3' and R.sup.4', together with the nitrogen atom, optionally forming a 5-, 6- or 7-membered saturated heterocyclic ring, the heterocyclic ring optionally including a second nitrogen atom and the heterocyclic ring being optionally substituted by phenyl or phenyl-C.sub.1 -C.sub.3 -alkyl,
• or a physiologically tolerated salt thereof, excluding the compounds in which R.sup.1' is the same as R.sup.3', with R.sup.1' and R.sup.3' denoting phenyl which is disubstituted by methyl and bromine and R.sup.2' being the same as R.sup.4', with R.sup.2' and R.sup.4' denoting hydrogen.

A method for treating a disturbance of the metabolism of collagen and collagen-like substances or the biosynthesis of Clq in a mammal comprising administering a pharmaceutically effective amount of a pyridine-2,4- or -2,5-dicarboxylic acid diamide of the formula I' ##STR12## in which R.sup.1' denotes branched or unbranched C.sub.1 -C.sub.12 -alkyl which is optionally monosubstituted or, in the case of C.sub.2 -C.sub.12 -alkyl, optionally polysubstituted by halogen, hydroxyl, cyano, amino, carboxyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyl- or dialkylamino, wherein the alkyl radicals contain 1-4 carbon atoms, and the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched, or indolyl or phenyl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, C.sub.1 -C.sub.4 -alkoxy or C.sub.1 -C.sub.4 -alkyl, the C.sub.3 - and C.sub.4 -alkyl radicals being optionally branched and in the case of polysubstitution, for the substituents to be the same or different, or

• R.sup.1' denotes saturated C.sub.5 -C.sub.7 -cycloalkyl, which is optionally benzo-fused, or
• R.sup.1' denotes aryl or heteroaryl, which is in turn optionally mono-, di- or trisubstituted by halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy, in the case of polysubstitution, the substituents being the same or different and in the case of the C.sub.3 - and C.sub.4 -alkyl radicals, the radicals being optionally branched, and
• R.sup.2', independently of R.sup.1', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.2' being optionally identical to R.sup.1',
• R.sup.3', independently of R.sup.1' and R.sup.2', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.3' being optionally identical to R.sup.1' or R.sup.2' or both, and
• R.sup.4', independently of R.sup.1', R.sup.2' and R.sup.3', is hydrogen or has one of the meanings described for R.sup.1', with R.sup.4', being optionally identical to R.sup.1', R.sup.2', R.sup.3', or any combination thereof, and in which the radicals R.sup.1' and R.sup.2' or R.sup.3' and R.sup.4', or R.sup.1', R.sup.2', R.sup.3' and R.sup.4', together with the nitrogen atom, optionally forming a 5-, 6- or 7-membered saturated heterocyclic ring, the heterocyclic ring optionally including a second nitrogen atom and the heterocyclic ring being optionally substituted by phenyl or phenyl-C.sub.1 -C.sub.3 -alkyl,
• or a physiologically tolerated salt thereof, excluding the compounds in which R.sup.1' is the same as R.sup.3', with R.sup.1' and R.sup.3' denoting phenyl which is disubstituted by methyl and bromine and R.sup.2' being the same as R.sup.4', with R.sup.2' and R.sup.4' denoting hydrogen.