Synthesis of 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide, a new [18F]fluorinated analogue of valdecoxib, as a potential radiotracer for imaging cyclooxygenase-2 with positron emission tomography.
Fluoroalkyl and fluoroaryl analogues of valdecoxib were found to possess potent inhibitory activities against cyclooxygenase-2 comparable to that of the parent valdecoxib. Among them, the fluoromethyl analogue was chosen for 18F-labeling. Thus, 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide (approximately 2000 Ci/mmol at end of synthesis) was synthesized by [18F]fluoride-ion displacement of the corresponding tosylate in approximately 40% decay-corrected radiochemical yield within approximately 120 min from end of bombardment.
Toyokuni
Tatsushi
T
Crump Institute for Molecular Imaging and LA Tech Center, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA. ttoyokuni@mednet.ucla.edu
Kumar
J S Dileep
JS
Walsh
Joseph C
JC
Shapiro
Alan
A
Talley
John J
JJ
Phelps
Michael E
ME
Herschman
Harvey R
HR
Barrio
Jorge R
JR
Satyamurthy
Nagichettiar
N
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000138:chemical synthesis*; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis*; D014018:Tissue Distribution; D000096926:Benzenesulfonamides
D016861:Cyclooxygenase Inhibitors; D005462:Fluorine Radioisotopes; D007555:Isoxazoles; D019275:Radiopharmaceuticals; D013449:Sulfonamides; C506411:4-(5-(18F)fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C406224:valdecoxib