Patent FR-2966151-A1 (FR)
Title: New 6-triazolopyridazine-sulfanyl benzothiazole compounds are met kinase inhibitors useful for treating e.g. metabolic disorders, allergies, asthma, thrombosis, nervous system diseases, retinopathy, psoriasis, diabetes and cancers
Inventor: BACQUE ERIC
IPC: A61K31/5025
Filed: 2010-10-14
Abstract: 6-Triazolopyridazine-sulfanyl benzothiazole compounds (I) and their isomeric forms, racemates, enantiomers, diastereoisomers, or addition salts with inorganic or organic acids or bases, are new. 6-Triazolopyridazine-sulfanyl benzothiazole compounds of formula (I) and their isomeric forms, racemates, enantiomers, diastereoisomers, or addition salts with inorganic or organic acids or bases, are new. R1 : alkyl, cycloalkyl or cycloalkylalkyl (al optionally substituted); R1b : H or F; W1 : alkyl, cycloalkyl or heterocycloalkyl (all optionally substituted by optionally substituted alkoxy, optionally substituted heterocycloalkyl or NR3R4), H or COR; R : cycloalkyl, heterocycloalkyl or alkyl (all optionally substituted by one or more cycloalkyl, heterocycloalkyl, heteroaryl, phenyl or NR3R4 (all optionally substituted), halo, OH or alkoxy), alkoxy (optionally substituted by optionally substituted alkyl, heterocycloalkyl or NR3R4), -O-heterocycloalkyl (optionally substituted), or NHR2; R2 : heterocycloalkyl, heteroaryl, phenyl or NR3R4 (all optionally substituted), cycloalkyl, heterocycloalkyl or alkyl (all optionally substituted by OH or alkoxy); either R3, R4 : alkyl, cycloalkyl, heterocycloalkyl, phenyl or heteroaryl (all optionally substituted by one or more OH, alkoxy, NH 2, NHAlk, N(Alk) 2or heterocycloalkyl), or heteroaryl or phenyl (both optionally substituted), or H; or NR3R4 : 3-10 membered ring containing optionally one or more other heteroatoms of O, S, N or NH, optionally S, optionally in the form of SO or SO 2, where the ring includes optional -NH-, which is optionally substituted; R5, R5a : alkyl or cycloalkyl (both optionally substituted by one or more halo or OH), 1-4C alkyl, 1-4C alkoxy, NH 2, NHAlk or N(Alk) 2group; and Alk, alkyl : 1-10C alkyl, where all the cycloalkyl groups are not more than 3-7C cycloalkyl groups. Where all the alkyl, cycloalkyl, heterocycloalkyl, -O-heterocycloalkyl, heteroaryl and phenyl groups in R3 and R4 may form with the nitrogen atom to which they are attached, are optionally substituted by one or more groups of halo, OH, oxo, alkoxy, -O-CO-R5, -COOH, COOR5, -CONH 2, CONHR5, NH 2, NHR5, NR5R5a, or -NH-CO-R5, and the alkyl, cycloalkyl, heterocycloalkyl, alkyl-heterocycloalkyl, CO-heterocycloalkyl, phenyl, CH 2-phenyl, CO-phenyl, heteroaryl or -S-heteroaryl, in which the alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl, are optionally substituted with one or more halo or OH, oxo, alkyl or 1-4C alkoxy, NH 2, NHAlk or N(Alk) 2; all the cycloalkyl, heterocycloalkyl, -O-heterocycloalkyl, phenyl and heteroaryl are optionally substituted by one or more Si(Alk) 3; and all the cycloalkyl and heterocycloalkyl can be optionally substituted on one of the carbon of ring by spirocycloalkyl group, or spiroheterocycloalkyl group (optionally two of the carbons of ring by a fused cycloalkyl or heterocycloalkyl). Independent claims are included for: (1) the preparations of (I); and (2) intermediates comprising benzothiazol-2-ylamine derivatives of formula (C), (D1)-(D6), (G), (K) and (M). [Image] [Image] [Image] ACTIVITY : Cytostatic; Antiinflammatory; Metabolic; Antiallergic; Antiasthmatic; Anticoagulant; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic; Muscular-Gen.; Antibacterial. MECHANISM OF ACTION : Met kinase inhibitor. The ability of (I) to inhibit met kinase was tested using homogeneous time-resolved fluorescence assay. The result showed that 6-[(6-cyclopropyl[1,2,4]triazolo[4,3-b]pyridazin-3-yl)sulfanyl]-1,3-benzothiazol-2-amine exhibited an IC 50value of less than 100 nM.