[摘要]：We report the synthesis and evaluation of a series of iodinated celecoxib analogues as cyclooxygenase-2 (COX-2)-targeted single photon emission computerized tomography (SPECT)-imaging agents for the detection of inflammation. The structure-activity relationship identified 5-(4-iodophenyl)-1-{4-(methylsulfonyl)-phenyl}-3-(trifuloromethyl)-1H-py razole (8) as a promising compound with IC50 values of 0.05 mu M against purified COX-2 and 0.03 mu M against COX-2 in activated macrophages. The arylstannane of 8-undergoes facile radio-[I-123]-iodination upon treatment with (NaI)-I-123/NaI and chloramine T using an EtOAc/H2O two-phase system. The [I-123]-8 was produced in a radiochemical yield of 85% and a radiochemical purity of 99%. In vivo SPECT imaging demonstrated that the radiotracer was taken up by inflamed rat paws with an average 1.7-fold enrichment over contralateral noninflamed paws. This study suggests that conversion of celecoxib into its isomeric iodo [I-123]-analogues is a useful approach for generating novel and efficacious agents for COX-2-targeted SPECT imaging of inflammation. |
