| 摘要 |
Pyrimidinylacetic acid derivatives (I) are new. Pyrimidinylacetic acid derivatives of formula (I), their tautomeric or stereoisomeric forms and salts are new. [Image] R 1 : -C(O)-(CH 2) n-Y', -C(O)-CH=CH-Y', -SO 2-(CH 2) n-Y', -CH 2-(CH 2) n-Y', -CH 2-CH=CH-Y', or -C(O)-NH-(CH 2) n-Y'; n : 0-6; Y' : H, 3-8C cycloalkyl (optionally substituted by 1-6C alkyl or optionally fused by benzene), or (hetero)aryl (optionally substituted by CN, halo, nitro, guanidino, pyrrolyl, sulfamoyl, 1-6C alkylaminosulfonyl, di(1-6C alkyl)aminosulfonyl, phenyloxy, phenyl, amino, 1-6C alkylamino, di-1-6C alkylamino, 1-6C alkoxycarbonyl, 1-6C alkanoyl, 1-6C alkanoylamino, carbamoyl, 1-6C alkylcarbamoyl, di-(1-6C alkyl)carbamoyl, 1-6C alkylsulfonyl, 1-6C alkyl (optionally mono- to tri-substituted by halo), 1-6C alkoxy (optionally mono- to tri-substituted by halo), 1-6C alkylthio (optionally mono- to tri-substituted by halo), or aryl (fused by 1,3-dioxolane)); R 2 : H or 1-6C alkyl; R 3 : q : 1-3; R 3 c : H, OH, carboxy, or 1-6C alkyl (optionally substituted by OH, carboxy, or (phenyl-substituted C1-6 alkyl)carbamoyl); X a : -O-, -S- or -N(R 3 d)-; R 3 d : 1-6C alkyl or -N(R 3 a)(R 3 b); R 3 a, R 3 b : 3-8C cycloalkyl, or 1-6C alkyl (optionally substituted by carboxy, 3-8C cycloalkyl, carbamoyl, 1-6C alkylcarbamoyl, aryl-substituted 1-6C alkylcarbamoyl, 1-6C alkylcarbamoyl, di(1-6C alkyl)carbamoyl, 3-8C cycloalkylcarbamoyl, 3-8C heterocyclocarbonyl, 1-6C alkylamino, di-1-6C alkylamino or 1-6C alkoxy); and R 4 : H, halo, 1-6C alkoxy, di(1-6C alkyl)amino or 1-6C alkyl (optionally mono- to tri-substituted by halo). ACTIVITY : Antiasthmatic; Antiallergic; Antiinflammatory; Dermatological; Ophthalmological; Cytostatic. MECHANISM OF ACTION : G-Protein-coupled chemoattractant receptor, expressed on Th2 cells (CRTH2) antagonist. [2-(4-Benzoylamino-benzyl)-4-chloro-6-(cyclopentylcarbamoylmethyl-methyl-amino)-pyrimidin-5-yl]-acetic acid (A) was tested for binding activity of human CRTH2 receptor. A cell suspension (2X10 5> cells) (100 mu l), [ 3>H]-labeled PGD 2, and (A) were mixed with 96-well U-bottom polypropylene plate and incubated for 60 minutes at room temperature to allow binding. After incubation, the cell suspension was transferred to a filtration plate and washed 3 times with binding buffer. Non-specific binding was determined. IC 5 0 of (A) was found to be = 0.5 nM. |
