New 2-benzyl-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 psychiatric disorders

摘要

2-Benzyl-imidazo[1,2-a]pyridine compounds (I) and their acid or base addition salts arenew. 2-Benzyl-imidazo[1,2-a]pyridine 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, OH, amino 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 2heterocyclic group (optionally substituted by OH, halo, 1-6C alkoxy, 1-6C alkyl optionally substituted by OH, NR cR d, CO-R 5, -CO-NR 6R 7, -CO-O-R 8, 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 a1-6C alkyl; and R 5, R 9, R 10, R b, R c, R dH or 1-6C alkyl. An independent claim is included for intermediate compounds (A) of (6-iodoimidazo[1,2-a]pyridine-2-yl)(phenyl)methanone and phenyl[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine-2-yl]methanone. [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 phenyl-[7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-2-yl]-methanone exhibited an EC 5 0value of 0.5 nM.