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.
