Patent FR-2933981-A1 (FR)
Title: New imidazo(1,2-a)pyridine derivatives are mesenchymal-epithelial transition protein kinase inhibitors useful in a pharmaceutical composition for preparing a medicament to treat/prevent e.g. fibrotic disorders, allergies and asthma
Inventor: DAMOUR DOMINIQUE
IPC: A61P17/06
Filed: 2008-07-18
Abstract: Imidazo[1,2-a]pyridine derivatives (I) and their isomers, racemic isomers, enantiomers, diastereomers and inorganic and organic acid or base addition salts are new. Imidazo[1,2-a]pyridine derivatives of formula (I) and their isomers, racemic isomers, enantiomers, diastereomers and inorganic and organic acid or base addition salts are new. Ra1 : aryl, heteroaryl (both optionally substituted), H or halo; Rb : H, Rc, -COORc, -CO-Rc or -CO-NRcRd; Rc : alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl (all optionally substituted); Rd : H, alkyl or cycloalkyl; either R1R2 : alkyl (optionally substituted by OH, alkoxy, NR3R4, heterocycloalkyl, heteroaryl or phenyl (optionally substituted)), cycloalkyl or H, where alkyl(alk) or alkoxy comprising 1-6C; and R3R4 : alkyl (optionally substituted by OH, alkoxy, heterocycloalkyl, heteroaryl or phenyl (optionally substituted)), cycloalkyl or H; or NR1R2 : 3-10 membered cyclic radical or optionally heteroatoms of O, S, N or NH; or NR3R4 : 3-10 membered cyclic radical or optionally heteroatoms of O, S, N or NH; or NR1R2, NR3R4 : cyclic radical optionally substituted by halo, OH, oxo, alkoxy, NH 2, NHalk, N(alk) 2, alkyl, phenyl, CH 2-phenyl or heteroaryl, such as alkyl, phenyl or heteroaryl optionally substituted by halo, OH, alkyl, 1-4C alkoxy, NH 2, NHalk or N(alk) 2. Provided that when: Rc is cycloalkyl, then it is optionally substituted by aryl or heteroaryl (both optionally substituted) or heterocycloalkyl; and Rc is alkyl, then it is optionally substituted by optionally substituted heterocycloalkyl. Where the: alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by halo, OH, alkoxy, CN, CF 3, -NR1R2, -COOH, -COOalk, -CONR1R2 or -NR1COR2; alkyl is optionally substituted by a radical, aryl or heteroaryl, which is optionally substituted by halo, OH, alkyl or NR3R4; and cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by alkyl, which is optionally substituted by halo, OH, alkyl, alkoxy or NR3R4. Independent claims are included for: (1) the preparations of (I); and (2) intermediate compounds comprising 3-bromo-imidazo[1,2-a]pyridine compound of formula (A), N-[4-(imidazo[1,2-a]pyridin-3-ylsul fanyl)-phenyl]-acetamide compound of formula (B), 4-(imidazo[1,2-a]pyridin-3-ylsulfanyl)-phenylamine compound of formula (C), [6-(6-methyl-imidazo[1,2-a]pyridin-3-ylsulfanyl)-benzothiazol-2-yl]-carbamic acid compound of formulae (D) and (E), (6-thiocyanato-benzothiazol-2-yl)-carbamic acid compound of formula (F1), (6-thiocyanato-benzothiazol-2-yl)-urea compound of formula (G) and (6-mercapto-benzothiazol-2-yl)-urea compound of formula (H). R : t-butyl or phenyl. [Image] [Image] [Image] [Image] ACTIVITY : Vasotropic; Antiinflammatory; Cytostatic; Metabolic; Antiallergic; Antiasthmatic; Anticoagulant; Thrombolytic; Neuroprotective; Ophthalmological; Antipsoriatic; Antiarthritic; Antirheumatic; Antidiabetic. MECHANISM OF ACTION : Mesenchymal-epithelial transition (MET) protein kinase inhibitor. The ability of (I) to inhibit MET protein kinase was tested using homogeneous time-resolved fluorescence assay. The result showed that the 6-{[6-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]sulfanyl}-1,3-benzothiazol-2-amine exhibited an IC 50value of less than 100 nM.