Patent FR-2925907-A1 (FR)
Title: New 2-heteroaryl-imidazo(1,2-a)pyridine compounds are nuclear receptor related protein 1 modulators useful for preparing medicament to treat and prevent e.g. neurodegenerative diseases, brain injuries, epilepsy and cancer
Inventor: PEYRONEL JEAN FRANCOIS
IPC: A61K31/437
Filed: 2008-01-02
Abstract: 2-Heteroaryl-imidazo[1,2-a]pyridine compounds (I) and their acid or base addition salts are new. 2-Heteroaryl-imidazo[1,2-a]pyridine compounds of formula (I) and their acid or base addition salts are new. X : benzodioxole or heteroaromatic group linked by C atom, optionally substituted by halo, 1-6C alkoxy, 1-6C alkyl or NR aR b; R 1H, halo, 1-6C alkoxy, 1-6C alkyl, OH or amino, where the alkyl or alkoxy is optionally substituted by one or more halo, OH, amino or 1-6C alkoxy; R 21-6C alkyl, 1-6C alkoxy (both optionally substituted by one or more OH, halo or NR aR b), 1-6C alkylthio, 2-6C alkenyl, 2-6C alkynyl, -CO-R 5, -CO-NR 6R 7, -CO-O-R 8, -NR 9-CO-R 1 0, -NR 1 1R 1 2, CN, phenyl (optionally substituted by one or more halo, 1-6C alkoxy or 1-6C alkyl (optionally substituted by OH, NR cR d, CO-R 5, -CO-NR 6R 7, -CO-O-R 8, halo or CN)) or heterocyclic group (optionally substituted by one or more OH, halo, 1-6C alkoxy or 1-6C alkyl (optionally substituted by OH, NR cR d, CO-R 5, -CO-NR 6R 7, -CO-O-R 8, -NR 9-CO-R 1 0, CN or oxido)); R 3H, halo, 1-6C alkyl or OH; R 4H or halo; either R 6, R 7H or 1-6C alkyl; or NR 6R 74-7 membered ring comprising optionally other heteroatoms of N, O or S; R 8, R 1 11-6C alkyl; R 5, R 9, R 1 0, R 1 2, R c, R dH or 1-6C alkyl; either R aR bH or 1-6C alkyl; or NR aR b4-7 membered ring comprising optionally other heteroatoms of N, O or S. An independent claim is included for intermediate compounds (A) of N-methoxy-N-methyl-6-chloroimidazo [1,2-a]pyridine-2-carboxamide, N-methoxy-N-methyl-5-methylimidazo [1,2-a]pyridine-2-carboxamide, N-methoxy-N-methyl-6-methylimidazo [1,2-a]pyridine-2-carboxamide, hydrobromide of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-pyridin-2-ylimidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-pyridin-2-yl-imidazo[1,2-a]pyridine-2-carboxylic acid and N-methoxy-N-methyl-6-pyridin-2-yl-imidazo[1,2-a]pyridine-2-carboxamide. [Image] ACTIVITY : Neuroprotective; Cerebroprotective; Anticonvulsant; Neuroleptic; Antiinflammatory; Osteopathic; Cytostatic; Antiparkinsonian; Nootropic; Antidepressant; Antiaddictive; Tranquilizer; CNS-Gen.; Vasotropic; Antiarteriosclerotic; Antiarthritic; Antirheumatic; Gastrointestinal-Gen; Antiulcer; Gastrointestinal-Gen.; Antiallergic; Antiasthmatic; Immunosuppressive; Antidiabetic; Dermatological; Endocrine-Gen; Immunusuppressant; Immunomodulator. MECHANISM OF ACTION : Nuclear receptor related protein 1 (NURR1) modulator; Hippocampus zinc finger protein 3 (HZF-3) modulator; Nuclear receptor of T-cells (NOT) modulator; Regenerating liver nuclear receptor 1 (RNR1) modulator; Transcriptionally inducible nuclear receptor (TINUR) modulator; Nuclear receptor subfamily 4, group A, member 2 (NR4A2) modulator. The ability of (I) to modulate nuclear receptor related protein 1 was tested using N2A cell lines. The results showed that the (7-chloroimidazo[1,2-a]pyridin-2-yl)(thien-2-yl)methanone exhibited an EC 5 0value of 4.7 nM.