New 6-triazolopyridazinesulfanyl benzothiazole and benzimidazole derivatives are Met kinase inhibitors, useful e.g. to treat/prevent fibrotic disorders, mesangial cell proliferation disorders, metabolic disorders, asthma and thrombosis

摘要

6-Triazolopyridazinesulfanyl benzothiazole and benzimidazole derivatives (I) and their racemic isomers, enantiomers, diastereomers, inorganic/organic acid addition salts, or inorganic/organic bases, are new. 6-Triazolopyridazinesulfanyl benzothiazole and benzimidazole derivatives of formula (I) and their racemic isomers, enantiomers, diastereomers, inorganic/organic acid addition salts, or inorganic/organic bases, are new. Bond with dotted lines : single or double bond; R a : H, halo, alkoxy (optionally substituted by Cl, OH or optionally substituted heterocycloalkyl), O-cycloalkyl, optionally substituted heteroaryl, phenyl, NHCOalk, NHCOcycloalk or NR 1R 2; X : S, SO or SO 2; A : NH or S; W 1 : H, alkyl (optionally substituted by alkoxy, heterocycloalkyl or NR 3R 4) or COR; R : cycloalkyl, alkyl (both optionally substituted by NR 3R 4, alkoxy, hydroxy, phenyl, heteroaryl or optionally substituted heterocycloalkyl), alkoxy (optionally substituted by NR 3R 4, alkoxy, hydroxy, heterocycloalkyl, O-phenyl or O-(CH 2) n-phenyl, where the phenyl is optionally substituted) or NR 1R 2; n : 1-4; either R 1, R 2 : H, alkyl (optionally substituted by OH, alkoxy, heteroaryl, heterocycloalkyl, NR 3R 4or optionally substituted phenyl) or cycloalkyl; or NR 1R 2 : 3-10 membered ring containing optionally one or more heteroatoms of O, S, N or NH; either R 3, R 4 : H, alkyl, cycloalkyl, heteroaryl or optionally substituted phenyl; or NR 3R 4 : 3-10 membered ring containing optionally one or more heteroatoms of O, S, N or NH (where heterocycloalkyl, heteroaryl, phenyl and the ring formed by R 1and R 2or R 3and R 4are optionally substituted by halo, OH, oxo, alkoxy, NH 2, NHalk, N(alk) 2, alkyl, cyloalkyl, heterocycloalkyl, CH 2-heterocycloalkyl, phenyl, CH 2-phenyl, heteroaryl, CO-phenyl or S-heteroaryl, such that in these radicals, the alkyl, heterocycloalkyl, phenyl and heteroaryl are optionally substituted by halo, OH, oxo, alkyl, 1-4C alkoxy, NH 2, NHalk or N(alk) 2). Independent claims are included for: (1) the preparations of (I); and (2) the use of (I) or their salts for the preparation of a medicament intended to inhibit the activity of Met protein kinase and its mutant forms. [Image] ACTIVITY : Cytostatic; Metabolic; Antiallergic; Antiasthmatic; Thrombolytic; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic; Antiinflammatory. MECHANISM OF ACTION : Met kinase inhibitor. The ability of (I) to inhibit Met kinase was tested using homogeneous time-resolved fluorescence assays. The result showed that IC 5 0value of (I) was 500 nM, preferably 100 nM.