| 摘要 |
#CMT# #/CMT# N-Phenyl-imidazo[1,2-a]pyridine-2-carboxamide compounds (I) and their acid or base addition salts are new. #CMT# : #/CMT# N-Phenyl-imidazo[1,2-a]pyridine-2-carboxamide compounds of formula (I) and their acid or base addition salts are new. X : phenyl substituted by CN, 1-6C alkoxycarbonyl, 1-6C alkoxy substituted by one or more halo, 1-6C alkyl substituted by one or more halo or phenyl (optionally substituted by halo); R 1H, halo, 1-6C alkoxy, 1-6C alkyl or NR aR b, 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 0or 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); 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 1 1, R 1 2H or 1-6C alkyl; or NR 1 1R 1 24-7 membered ring comprising optionally other heteroatoms of N, O or S; either R aR bH or 1-6C alkyl; or NR aR b4-7 membered ring. Provided that (I) excludes the compound in which R 1and R 3are methyl or R 2is Cl. 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-(3-hydroxymethyl-phenyl)-imidazo[1,2-a]pyridine-2-ethyl carboxylate and 6-(3-hydroxymethyl-phenyl)-imidazo[1,2-a]pyridine-2-carboxylic acid. #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# 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. #CMT#MECHANISM OF ACTION : #/CMT# 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 N-(2-cyano-3-fluorophenyl)-6-[3-(hydroxymethyl)phenyl]imidazo[1,2-a]pyridine-2-carboxamide exhibited an EC 5 0value of 0.4 nM. #CMT#USE : #/CMT# (I) are useful for preparing a medicament intended to treat and prevent neurodegenerative diseases, brain injuries, epilepsy, psychiatric disorders, inflammatory diseases, osteoporosis, cancer, Parkinson disease, Alzheimer diseases, tauopathies, multiple sclerosis, schizophrenia, depression, substance dependence disorders and attention deficit hyperactivity disorder. (A) are useful for the preparation of products of (I) (all claimed), where the inflammatory diseases includes: CNS inflammatory diseases such as encephalitis, myelitis and encephalomyelitis; other inflammatory diseases such as vascular diseases, atherosclerosis, joints inflammation, osteoarthritis, rheumatoid arthritis, Crohn's disease and ulcerative colitis; and allergic inflammatory diseases such as asthma, autoimmune diseases such as type 1 diabetes, lupus, scleroderma, Guillain-Barre syndrome, Addison's disease. (I) are useful treat and prevent other immune-mediated diseases. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (Disclosed): Preparation of (I) comprises reacting 2-amino-pyridine compound of formula (II) with halo compound of formula (Hal-CH 2-C(=O)-C(=O)-NH-X) (III) to give (I). Hal : Cl, Br or I. #CMT#[Image]#/CMT# #CMT#DEFINITIONS : #/CMT# Preferred Definitions: X : phenyl substituted by CN, CO 2CH 3or OCF 3, where the phenyl is optionally substituted by F; R 1, R 3, R 4H; and R 2N-dimethyl or phenyl substituted by hydroxymethyl. #CMT#ADMINISTRATION : #/CMT# Administration of (I) is 50 mg, orally, sublingually, subcutaneously, intramuscularly, intravenously, topically, locally, intratracheally, intranasally, transdermally or rectally. #CMT#SPECIFIC COMPOUNDS : #/CMT# 9 Compounds (I) are disclosed e.g. N-(3-cyano-5-fluorophenyl)-7-[3-(hydroxymethyl)phenyl]imidazo[1,2-a]pyridine-2-carboxamide of formula (Ia), N-(3-cyanophenyl)-7-(dimethylamino)imidazo[1,2-a]pyridine-2-carboxamide, 3-({[7-(dimethylamino)imidazo[1,2-a]pyridin-2-yl] carbonyl}amino)methyl benzoate, N-(4-cyano-2-fluorophenyl)-7-dimethylamino-imidazo[1,2-a]pyridine-2-carboxamide and N-(3-cyano-5-fluorophenyl)-7-dimethylamino-imidazo[1,2-a]pyridine-2-carboxamide. #CMT#[Image]#/CMT# #CMT#EXAMPLE : #/CMT# A suspension of 6-dimethylamino-imidazo[1,2-a]pyridine-2-carboxylic acid (120 mg) and hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (224 mg) in anhydrous pyridine (2 ml) was placed under argon and then methyl 3-aminobenzoate (265 mg) was added. The reaction mixture was stirred for 48 hours at 50[deg] C and then concentrated to dryness under reduced pressure. The residue was taken up by chloroform (5 ml) and washed with water (2 ml). The resulting mixture was worked up to give 3-({[6-(dimethylamino)imidazo[1,2-a]pyridin-2-yl] carbonyl}amino)methyl benzoate (105 mg). |
