New triazolo(4,3-a)pyridine derivatives are Met protein kinase inhibitors useful to treat e.g. fibrotic disorders, metabolic disorders, allergies, asthma, thrombosis, retinopathy, psoriasis, rheumatoid arthritis, diabetes and cancer

摘要

Triazolo(4,3-a)pyridine derivatives (I) and their all possible isomeric forms, racemates, enantiomers and diastereoisomers, and addition salts with organic or inorganic acid and bases, are new. Triazolo(4,3-a)pyridine derivatives of formula (I) and their all possible isomeric forms, racemates, enantiomers and diastereoisomers, and addition salts with organic or inorganic acid and bases, are new. R1a : aryl or heteroaryl (both optionally substituted), H or halo; R1b : H, R1c, -COOR1c, CO-R1c or CO-NR1cR1d; R1c : alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted); one of R 1 and R 2 : H or alkyl; and other of R 1 and R 2 : cycloalkyl or alkyl (both optionally substituted by one or more OH, alkoxy, NR 3R 4, heterocycloalkyl, heteroaryl or phenyl (all optionally substituted)) or H; or NR 1R 2 : 3-10 membered ring optionally containing one or more other heteroatoms(s) comprising O, S, N or NH, and including the possible substituted NH group; one of R 3 and R 4 : H or alkyl; and other of R 3 and R 4 : H, cycloalkyl or alkyl (optionally substituted by one or more OH, alkoxy, heterocycloalkyl, heteroaryl or phenyl (all optionally substituted)); or NR 1R 2 : 3-10 membered ring optionally containing one or more other heteroatoms(s) comprising O, S, N or NH, and including the possible substituted NH group; and R1d : alkyl, cycloalkyl or H, where the cycloalkyl, heterocycloalkyl, heteroaryl or aryl being optionally substituted by halo, OH, alkoxy, CN, CF 3, -NR 1R 2, COOH, -COOalk, -CONR 1R 2, -NR 1COR 2 or heterocycloalkyl, alkyl and cycloalkyl being optionally substituted by one or more aryl or heteroaryl (both optionally substituted by one or more radicals of halo or OH, alkyl, alkoxy or NR 3R 4), alkyl and cycloalkyl being optionally substituted by one or more aryl or heteroaryl (both optionally substituted by one or more radicals of halo or OH, alkyl, alkoxy or NR 3R 4), cycloalkyl, heterocycloalkyl, heteroaryl or aryl being optionally substituted by alkyl (optionally substituted by one or more halo, OH, alkyl, alkoxy or NR 3R 4), the ring formed by R 1 and R 2 or R 3 and R 4 with the nitrogen atom is optionally substituted by alkyl, phenyl, CH 2-phenyl or heteroaryl (all optionally substituted by one or more halo, OH, alkyl, 1-4C alkoxy, NH 2, NHalk, N(alk) 2, halo, OH, oxo, alkoxy, NH 2, NHalk, or N(alk) 2), and all the alkyl(alk) and alkoxy containing 1-6C. Independent claims are included for: (1) the preparations of (I); and (2) intermediates comprising [1,2,4]triazolo[4,3-a]pyridine-3-thiol compound of formula (A), 3-(4-nitro-phenylsulfanyl)-[1,2,4]triazolo[4,3-a]pyridine compound of formula (B), 3-(4-amino-phenylsulfanyl)-[1,2,4]triazolo[4,3-a]pyridine compound of formula (C), [6-(triazolo[4,3-a]pyridin-3-ylsulfanyl)-benzothiazol-2-yl]-carbamic acid compound of formula (D) or (E), 2-methylamino-benzothiazole-6-diazonium compound of formula (H), N-(6-thiocyanato-benzothiazol-2-yl)-acetamide compound of formula (J), N-(6-mercapto-benzothiazol-2-yl)-acetamide compound of formula (K), 3-bromo-triazolo[4,3-a]pyridine compound of formula (L), or triazolo[4,3-a]pyridine compound of formula (L1). [Image] [Image] [Image] [Image] [Image] ACTIVITY : Antiinflammatory; Cytostatic; Metabolic; Antiallergic; Antiasthmatic; Anticoagulant; Thrombolytic; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic; Muscular-Gen. MECHANISM OF ACTION : Met protein kinase inhibitor. The ability of (I) to inhibit Met kinase was tested using an enzyme-linked-immunosorbent serologic assay. The results showed that 6-{[6-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]sulfanyl}-1,3-benzothiazol-2-amine exhibited an IC 50 value of 1-10~mM.