Patent FR-2925903-A1 (FR)
Title: New 6-heterocyclic-imidazo(1,2-a)pyridine-2-carboxamide compounds are nuclear receptor related protein 1 modulators useful for preparing a 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: 6-Heterocyclic-imidazo[1,2-a]pyridine-2-carboxamide compounds (I) and their acid or base addition salts are new. 6-Heterocyclic-imidazo[1,2-a]pyridine-2-carboxamide compounds of formula (I) and their acid or base addition salts are new. X : phenyl (optionally substituted by 1-6C alkyl, 1-6C alkoxy (both optionally substituted by halo), halo, NR aR b, CN or 1-6C alkoxycarbonyl); R 1 : 1-6C alkoxy, 1-6C alkyl (both optionally substituted by halo, OH, amino or 1-6C alkoxy), H, halo or NR aR b; R 2 : heterocyclic group (optionally substituted by OH, 1-6C alkoxy, halo, CN, NR aR b, -CO-R 5, -CO-NR 6R 7, -COOR 8, -NR 9-CO-R 10, 3-7C cycloalkyl-1-6C alkyl, 3-7C cycloalkyl-1-6C alkoxy, oxido or 1-6C alkyl optionally substituted by OH or NR aR b); R 3 : H, 1-6C alkyl, 1-6C alkoxy or halo; R 4 : H, 1-4C alkyl, 1-4C alkoxy or F; R 5 : H, phenyl or 1-6C alkyl; either R 6, R 7 : H or 1-6C alkyl; or NR 6R 7 : 4-7 membered ring comprising optionally other heteroatoms of N, O or S; R 8 : 1-6C alkyl; R 9, R 10 : H or 1-6C alkyl; either R aR b : H or 1-6C alkyl; or NR aR b : 4-7 membered ring comprising optionally other heteroatoms of N, O or S. Provided that (I) excludes N-(4-bromophenyl)-6-(1-methyl-2-piperidinyl)imidazo[1,2-a]pyridine-2-carboxamide. An independent claim is included for 49 intermediate compounds (A) e.g. 6-bromo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, 6-iodo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, N-phenyl-6-cyano-imidazo[1,2-a]pyridine-2-carboxamide, 6-trimethylstannyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, hydrobromide of N-phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-imidazo[1,2-a]pyridine-2-carboxamide, hydrochloride of 2-phenylcarbamoyl-imidazo[1,2-a]pyridine-6-boronic acid, N-phenyl-6-vinylimidazo[1,2-a]pyridine-2-carboxamide, 6-formyl-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, 6-(2-bromo-acetyl)-N-phenyl-imidazo[1,2-a]pyridine-2-carboxamide, 6-(1-ethoxyvinyl)-N-pheylimidazo[1,2-a]pyridine-2-carboxamide, N-(3,5-difluorophenyl)-6-iodoimidazo[1, 2-a]pyridine-2-carboxamide, 6-(6-{[(1,1-dimethylethoxy)carbonyl]amino}pyridin-2-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(6-aminopyridin-2-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-(6-{[(1,1-dimethylethoxy)carbonyl]amino}pyridin-2-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-(6-{bis[(1,1-dimethylethoxy)carbonyl]amino}pyridin-2-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, (6-pyridin-2-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, (6-pyridin-2-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylic acid and 6-(2-{[(1,1-dimethylethoxy)carbonyl]amino}-thiazol-4-yl)imidazo[1,2-a]pyridine-2-ethyl carboxylate. [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-(1H-[1,2,4]triazol-3-yl)-imidazo[1,2-a]pyridine-2-carboxylic acid (3-fluoro-phenyl)-amide exhibited an EC 5 0value of 0.4 nM.