| 摘要 |
Disclosed are 8-([Hetero]aryl)-6-(4-alkyl-piperazin-1-yl)-9H-purine derivatives as represented by the general formula (I), wherein R1 is selected from H, F, Cl, alkyl, CF3, cyclopropyl, OCH3, OCF3 and CN; R2 is selected from tetrahydrofuranyl, tetrahydropyranyl, azetidine-1-carboxylic acid methyl ester and tetrahydrothiophene-1,1-dioxide; R3 is H or combines with R4 to form a fused pyrrolidin-2-one; R4 is selected from alkyl, fluoroalkyl, cyclopropyl and COCH3; R5 is selected from H, CH3 and CF3; n is 0 or 1; X1 and X3 are independently selected from N, CH and CR6; X2 is selected from CH and CR6; with the proviso that only one of X1, X2 and X3 may be other than CH; R6 is selected from F, Cl, CF3, OCH3 and OCF3; or a pharmaceutically acceptable salt thereof. Representative compounds include 8-(2-chloro-pyridin-3-yl)-2-methyl-6-(4-methyl-piperazin-1-yl)-9-(R)-tetrahydro-furan-3-yl-9H-purine, 2-methyl-6-(4-methyl-piperazin-1-yl)-9-(tetrahydro-pyran-4-yl)-8-(2-trifluoromethylphenyl)-9H-purine and 8-(2-chloro-phenyl)-2-methyl-6-(4-methyl-piperazin-1-yl)-9-(tetrahydro-pyran-4-yl)-9H-purine. Also disclosed is a pharmaceutical composition which comprises a compound as defined above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier, for the treatment of pain and osteoarthritic pain.
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