New heterocyclyl substituted triazolo(4,3-b)pyridazine compounds are Met protein kinase inhibitors useful to treat e.g. allergies, asthma, thrombosis, retinopathy, psoriasis, rheumatoid arthritis, diabetes, muscle degeneration and cancer

摘要

Heterocyclyl substituted triazolo[4,3-b]pyridazine compounds (I) and their isomers, racemic forms, enantiomers, diastereoisomers, or mineral or organic acid addition salts or bases, are new. Heterocyclyl substituted triazolo[4,3-b]pyridazine compounds of formula (I) and their isomers, racemic forms, enantiomers, diastereoisomers, or mineral or organic acid addition salts or bases, are new. dotted line : single bond or absent; R1a : H, halo or phenyl (optionally substituted); X : S (preferred), O or SO 2; A : NH or S; W 1>H or COR radical; R : cycloalkyl, alkyl (optionally substituted by phenyl, heteroaryl, NR 3>R 4>or optionally substituted heterocycloalkyl), alkoxy radical (optionally substituted by NR 3>R 4>, -O-(CH 2) nNR 3>R 4>, -O-phenyl or -O-(CH 2) n-phenyl); either R 1>, R 2>H, cycloalkyl, alkyl (optionally substituted by OH, alkoxy, heteroaryl, heterocycloalkyl, NR 3>R 4>or optionally substituted phenyl); or NR 1>R 2>cyclic radical optionally containing one or more heteroatoms of O, S, N or NH, where the radical has optionally substituted NH; either R 3>, R 4>H, alkyl, cycloalkyl, heteroaryl radical or phenyl (optionally substituted); or NR 3>R 4>cyclic radical optionally containing one or more heteroatoms of O, S, N or NH, where the radical has optionally substituted NH; and n : 1-4. Where the heterocycloalkyl, heteroaryl and phenyl in R1 and R2 or R3 and R4 form cyclic radical with the nitrogen atom, and the cyclic radical is optionally substituted by one or more radical comprising alkyl, cycloalkyl, CH 2-heterocycloalkyl, CH 2-phenyl, CO-phenyl or S-heteroaryl (all optionally substituted by alkyl, heterocycloalkyl, phenyl or heteroaryl (all optionally substituted by halo, OH, oxo, alkyl, 1-4C alkoxy, NH 2, NHalk or N(alk) 2), halo, OH, oxo, alkoxy, NH 2, NHalk or N(alk) 2). An independent claim is included for the preparation of (I). [Image] ACTIVITY : Metabolic; Antiallergic; Antiasthmatic; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic; Cytostatic; Prevention: Anticoagulant/Treatment: Thrombolytic. MECHANISM OF ACTION : Met protein kinase inhibitor. The ability of (I) to inhibit Met protein kinase was tested in MKN45 cells using enzyme-linked immunosorbent assay. The result showed that (6-([6-(4-fluorophenyl) [1,2,4] triazolo [4,3-b]pyridazin-3-yl]sulfanyl)-1,3-benzothiazol-2-yl) methyl carbamate exhibited an IC 5 0value of less than 1 mu M.