New 4-cyano-2-sulfonylphenyl-pyrazolyl-substituted pyridinones and pyrazinones compounds are human neutrophil elastase inhibitors, useful to treat and prevent e.g. pulmonary arterial hypertension and chronic obstructive pulmonary disease

摘要

4-Cyano-2-sulfonylphenyl-pyrazolyl-substituted pyridinone and pyrazinone compounds (I) are new. 4-Cyano-2-sulfonylphenyl-pyrazolyl-substituted pyridinone and pyrazinone compounds of formula (I) and their salts, solvates or solvates of the salts, are new. A : CH or N; R1 : CH 3or ethyl; R2, R3 : (1-4C)-alkyl or H; R4 : H, F or Cl; and R5 : (1-6C)-alkyl (optionally substituted with (1-4C)-alkoxy, di(1-4C)-alkylamino, (3-6C)-cycloalkyl, phenyl or 6-membered heteroaryl or up to five times with F). Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with one or more inert, non-toxic excipients. [Image] ACTIVITY : Hypotensive; Respiratory-Gen.; CNS-Gen.; Antiasthmatic; Antiinflammatory; Antitussive; Virucide; Antiallergic; Cardiant; Vasotropic; Antibacterial; Immunosuppressive; Antiarteriosclerotic; Uropathic; Antiarthritic; Antirheumatic; Dermatological; Ophthalmological; Anticoagulant; Thrombolytic; Nephrotropic; Antiarrhythmic; Cerebroprotective; Antilipemic; Hemostatic; Analgesic; Antianginal; Antidiabetic; Metabolic; Anorectic; Cytostatic; Gastrointestinal-Gen.; Antidiarrheic; Hepatotropic; Neuroprotective; Nootropic; Antiparkinsonian; Anticonvulsant; Antidepressant; Immunomodulator; Antithyroid; Antipsoriatic; Antiseborrheic; Osteopathic. MECHANISM OF ACTION : Human neutrophil elastase inhibitor; Cytochrome P450 inhibitor. The human neutrophil elastase inhibiting activity of (I) was tested in vitro. The results showed that 5-{1-[4-cyano-2-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridin-3-carboxamide exhibited an IC 50value of 0.5 nM.