| 摘要 |
Carboxylic acid amides (I), their optical antipodes, racemates and salts are new. Carboxylic acid amides of formula (I), their optical antipodes, racemates and salts are new. [Image] (CHR 1>) m and (CHR 2>) 2CH 2-CH 2; V,U : H or halo, OH, CN, NO 2, amino or 1-4 alkylamino, arylamino, aralkylamino, 1-4C alkylsulfonamido or 1-4C alkanoylamido (all optionally substituted by one or more halo), arylsulfonamido, 1-4C alkylsulfonyloxy, carboxy, CF 3, CF 3O, 1-4C alkyl-SO 2-NH-CH 2, NH 2-(CH 2) 1 - 4 4-SO 2NH-, NH 2-(CH 2) 1-4-(CO)-NH, sulfamoyl, [NH 2-SO 2], formyl, [-CHO], aminomethyl, [CH 2-NH 2], hydroxymethyl, 1-4C alkyl, 1-4C alkoxymethyl, halogenmethyl, tetrazolyl group, or 1-4C alkoxy, 1-4C alkoxycarbonyl, 1-6C alkanoyloxy, phenyl or 1-4C alkoxy, optionally substituted by NH 2; or neighbouring V and U groups with one or more heteroatom and CH= and/or CH 2 groups : an optionally substituted 4-7 membered homo- or heterocyclic ring, preferably morpholne, pyrrole, pyrrolidine, oxo- orthioxo-pyrrolidine, pyrazole, pyrazolidine, imidazole, imidazolidine, oxo- or thioxo-imidazole, imidazolidine, 1,4-oxazine, oxazole, oxazolidine, oxo or thioxo-oxazolidine, or 3-oxo-1,4-oxazine ring; W, X = CO, CH 2; : -CH(alkyl) where alkyl is 1-4C alkyl with the restriction that W and X cannot both be methylene at the same time; Y : O, 1-4C alkylene, 1-4C alkynylene, cycloalkylene, aminocarbonyl, -NH-, -N(alkyl), -CH 2O-, -CH(OH)-, OCH 2 where alkyl is 1-4C alkyl; Z' : H or halo, nitro, NH 2, 1-4C alkyl, 1-4C alkoxy, CN, CF 3, OH or carboxy; n : 0-3; R 1>, R 2>H or alkyl; or R 1> + R 2>optionally substituted 1-3 alkylene bridge. With the proviso when Z is H, Y is CH 2, both of m and n are 2, both of R 1> and R 2> are H, W is CO, X is CH 2 and V is H, then U is other than a 4-bromo-substituent; and when Z' is H, Y is CH 2, both of m and n are 2, both of R 1> and R 2> are H, both of W of W and X are CO and V is H, then U is other than 4-carboxyl or 4-ethoxycarbonyl. ACTIVITY : Analgesic; Anxiolytic; Cerebroprotective; Antidepressant; Ophthalmological: Antiparkinsonian; Antiaddictive; Neuroprotective; Nootropic; Anticonvulsant; Antidiabetic; Antiasthmatic; Auditory. In a mouse formalin test in which injection of formalin into the hind paw elicited biphasic pain, 2-{4-(4-fluoro-benzyl)-piperidin-1-yl]-2-oxo-N(2-oxo-2,3-dihydro-1H-indol-5-yl)acetamide (Ia) had an ED 5 0 of 0.46 mg/kg p.o., cf. greater than 20 mg/kg for a reference compound 6-{2-[4-(4-fluoro-benzyl)-piperidin-1-yl]-ethanesulfinyl}-3H-benzoxazolo-2-one. MECHANISM OF ACTION : (N-Methyl-D-aspartate) NMDA receptor antagonist. |
