Substituted pyridones and pyrazinones and their use as inhibitors of neutrophil elastase activity

摘要

Substituted 2-pyridones and pyrazinones of formula 1;
and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other auto-immune and allergic disorders, allograft rejection and oncological diseases.

主权项

1. A compounds of the formula 1 wherein A is phenyl or a five- or six-membered, aromatic heteroring comprising one, two or three heteroatoms independently selected from the group consisting of N, (O−)—N+, O and S; R1 is selected from the group consisting of R1.1 is C1-4-alkyl-, C3-6-cycloalkyl- or C1-4-haloalkyl-;R1.2 is selected from the group consisting of H, NC—, O2N—, C1-4-alkyl-, C3-6-cycloalkyl-, C1-4-alkyl-(O)C—, C3-6-cycloalkyl-(O)C—, H2N—(O)C—, C1-4-alkyl-NH—(O)C—, C3-6-cycloalkyl-NH—(O)C—, C1-4-alkyl-O—(O)C—, C3-6-cycloalkyl-O—(O)C—, H2N—(HO—N)C—, morpholinyl-(O)C— and C1-4-alkyl-SO2—,
or a 5-membered aromatic heterocycle containing one, two or three atoms selected from the group consisting of N, O and S; each ring optionally substituted with one or two residues selected independently from each other from the group consisting of C1-4-alkyl-, C3-6-cycloalkyl-, halogen and C1-4-haloalkyl-;R1.3 is selected from the group consisting of H, C1-4-alkyl-, C3-6-cycloalkyl-, C1-4-alkyl-O—, C3-6-cycloalkyl-O—, benzyl-, H2N—, C1-4-alkyl-NH— and (C1-4-alkyl-)2N—;
or two R1.3 are together C2-5-alkylene forming a carbocyclic heteroring;R1.4 is C1-4-alkyl- or C3-6-cycloalkyl-;R1.5 is selected from the group consisting of H, NC—, C1-4-alkyl-, C3-6-cycloalkyl- and C1-4-alkyl-O—C1-4-alkyl-;x is 0 or 1; R2 is phenyl or pyridyl, each ring optionally substituted with one or two residues selected independently from each other from the group consisting of C1-4-alkyl-, halogen and C1-4-haloalkyl-; R3 is selected from the group consisting of C1-4-alkyl-, C3-6-cycloalkyl-, C1-4-haloalkyl- and C1-4-alkyl-O—C1-4-alkyl-;
or phenyl or pyridyl, each ring optionally substituted with one or two residues selected independently from each other from the group consisting of NC—, halogen, C1-4-alkyl- and C1-4-haloalkyl-; Y is CH or N; or a salt thereof.