Patent FR-2925904-A1 (FR)
Title: New N-heterocyclic-imidazo(1,2-a)pyridine-2-carboxamide 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: N-Heterocyclic-imidazo[1,2-a]pyridine-2-carboxamide compounds (I) and their acid or base addition salts are new. N-Heterocyclic-imidazo[1,2-a]pyridine-2-carboxamide compounds of formula (I) and their acid or base addition salts are new. X : heterocyclic group optionally substituted by halo, 1-6C alkoxy, 1-6C alkyl, NR aR b, CN, oxido or COOR 8, where the alkyl or alkoxy is optionally substituted by halo; R 1H, halo, 1-6C alkoxy, 1-6C alkyl, amino or NR aR b, where the alkyl or alkoxy is optionally substituted by halo, OH, amino or 1-6C alkoxy; R 2either a heterocyclic or a heteroaromatic group (both optionally substituted by OH, 1-6C alkyl, 1-6C alkoxy, CN, NR aR b, -CO-R 5, -CO-NR 6R 7, -CO-O-R 8or -NR 9-CO-R 1 0, where the alkyl or alkoxy is optionally substituted by halo, OH, NR aR bor oxido); R 3H, 1-6C alkyl, 1-6C alkoxy or halo; R 4H, 1-4C alkyl, 1-4C alkoxy or F; R 5H, phenyl or 1-6C alkyl; 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 81-6C alkyl; R 9, R 1 0H 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 6-(6-{[(1,1-dimethylethoxy)carbonyl]amino}pyridin-2-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, (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-carboxylic acid, 6-(2-{[(1,1-dimethylethoxy)carbonyl]amino}-thiazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1H-pyrrol-3-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(furan-2-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(furan-3-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-[5-(hydroxymethyl)furan-2-yl]imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(thiophen-3-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(oxazol-2-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1H-1,2, 4-triazol-3-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-(1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylic acid, 6-iodo-N-(isoxazol-4-yl)imidazo[1,2-a]pyridine-2-carboxamide, 6-iodo-N-(thiazol-2-yl)imidazo[1,2-a]pyridine-2-carboxamide, 6-iodo-N-(pyridin-2-yl)imidazo[1,2-a]pyridine-2-carboxamide, 6-trimethylstannyl-N-(pyridin-2-yl)imidazo[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 and 2-ethoxycarbonyl-imidazo[1,2-a]pyridine-6-boronic acid. [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-imidazol-4-yl)-N-(pyridin-2-yl)imidazo[1,2-a]pyridine-2-carboxamide exhibited an EC 5 0value of 0.8 nM.