Patent FR-2945806-A1 (FR)
Title: New imidazo(1,2-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: 2009-05-19
Abstract: Imidazo[1,2-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. Imidazo[1,2-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>, R 2> : H or alkyl; and other of R 1>, R 2> : H, cycloalkyl or alkyl (optionally substituted by one or more OH, alkoxy, NR 3>R 4>, heterocycloalkyl, heteroaryl or phenyl (all optionally substituted by halo, OH, alkyl, alkoxy, NH 2, NHalk or N(alk) 2); 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 optionally 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 by OH, alkyl, alkoxy, NH 2, NHalk or N(alk) 2); 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 optionally 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>, COR 1>, oxo or heterocycloalkyl (optionally substituted by one or more halo, OH, CN, CF 3, -NR 2>R 3>, COOH, -COOalk, -CONR 3>R 4>, -NR 3>COR 4>, COR 3>, or oxo), 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 or 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 or N(alk) 2), halo, OH, oxo, alkoxy, NH 2, NHalk or N(alk) 2), halo, OH, oxo, alkoxy, NH 2, NHalk, and N(alk) 2, and all the alkyl(alk) and alkoxy contain 1-6C. Independent claims are included for: (1) the preparations of (I); and (2) intermediates comprising 3-bromo-imidazo[1,2-a]pyridine compound of formula (A), N-[4-(imidazo[1,2-a]pyridin-3-ylsulfanyl)-phenyl]-acetamide compound of formula (B), 4-(imidazo[1,2-a]pyridin-3-ylsulfanyl)-phenylamine compound of formula (C), [6-(imidazo[1,2-a]pyridin-3-ylsulfanyl)-benzothiazol-2-yl]-carbamic acid compound of formula (D) or (E), (6-thiocyanato-benzothiazol-2-yl)-carbamic acid compound of formula (F), (6-thiocyanato-benzothiazol-2-yl)-urea compound of formula (G), (6-mercapto-benzothiazol-2-yl)-urea compound of formula (H), N-(6-thiocyanato-benzothiazol-2-yl)-acetamide compound of formula (J), and N-(6-mercapto-benzothiazol-2-yl)-acetamide (K). R : tert-butyl or phenyl. [Image] [Image] [Image] [Image] ACTIVITY : Cytostatic; Metabolic; Antiallergic; Antiasthmatic; Anticoagulant; Thrombolytic; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic; Muscular-Gen.; Antiinflammatory. MECHANISM OF ACTION : Met protein kinase inhibitor. The ability of (I) to inhibit Met kinase was tested using a 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 mu M.