Patent FR-2925902-A1 (FR)
Title: New 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 psychiatric disorders
Inventor: PEYRONEL JEAN FRANCOIS
IPC: A61K31/437
Filed: 2008-01-02
Abstract: Imidazo[1,2-a]pyridine-2-carboxamide compounds (I) and their acid or base addition salts are new. Imidazo[1,2-a]pyridine-2-carboxamide compounds of formula (I) and their acid or base addition salts are new. NXY 1saturated or partially saturated 5-10 membered mono- or bi-cyclic amine comprising optionally 1-4 heteroatoms of N, O or S, optionally substituted by 1-6C alkoxy, 1-6C alkyl (both optionally substituted by halo), halo, CN, NR aR bor COOR 8; R 1H, halo, 1-6C alkoxy, 1-6C alkyl, NR cR d, where the alkyl or alkoxy is optionally substituted by one or more halo, OH, amino or 1-6C alkoxy; R 2H, 1-6C alkyl (optionally substituted by one or more OH, halo, amino, NR aR b, 1-6C alkoxy or phenyl), 1-6C alkoxy (optionally substituted by one or more OH, halo, amino or NR aR b), 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, -N=CH-NR aR b, halo, CN, nitro, hydroxyiminoalkyl, alkoxyiminoalkyl, 1-6C alkylthio, 1-6C alkylsulfinyl, 1-6C alkylsulfonyl, ((1-6C alkyl) 3)silylethynyl, -SO 2-NR 9R 1 0, phenyl (optionally substituted by one or more halo, 1-6C alkoxy, CN, NR aR b, -CO-R 5, -CO-NR 6R 7, -CO-O-R 8, 3-7C cycloalkyl-1-6C alkyl, 3-7C cycloalkyl-1-6C alkoxy or 1-6C alkyl optionally substituted by OH or NR aR b) or heterocyclic group (optionally substituted by one or more 1-6C alkoxy, 1-6C alkyl (both optionally substituted by halo), halo, CN, NR aR bor COOR 8); R 3H, 2-6C 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; R 1 1, R 1 2H or 1-6C alkyl; either R aR bH or 1-6C alkyl; or NR aR b4-7 membered ring; R cH; and R d1-6C alkyl. Provided that (I) excludes 2-(2,3-dihydro-1H-indol-1-ylcarbonyl)-5-methylimidazo[1,2-a]pyridine. An independent claim is included for the compounds (A) of 6-dimethylamino-imidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-dimethylamino-imidazo[1,2-a]pyridine-2-carboxylic acid, 6-methoxy-5-methylimidazo[1,2-a]pyridine-2-ethyl carboxylate, 6-methoxy-5-methylimidazo[1,2-a]pyridine-2-carboxylic acid, 6-(3-hydroxymethyl-phenyl)-imidazo[1,2-a]pyridine-2-ethyl carboxylate and 6-(3-hydroxymethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic 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-(3-hydroxymethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid (3,6-dihydro-2H-pyridin-1-yl)-amide exhibited an EC 5 0value of 0.8 nM.