Patent FR-2941229-A1 (FR)
Title: 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
Inventor: DAMOUR DOMINIQUE
IPC: A61K31/437
Filed: 2009-01-21
Abstract: 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 3>R 4>, heterocycloalkyl, heteroaryl or phenyl (all optionally substituted)) or H; or NR 1>R 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 1>R 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 1>R 2>, COOH, -COOalk, -CONR 1>R 2>, -NR 1>COR 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 3>R 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 3>R 4>), cycloalkyl, heterocycloalkyl, heteroaryl or aryl being optionally substituted by alkyl (optionally substituted by one or more halo, OH, alkyl, alkoxy or NR 3>R 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.