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

• Published in: Bioorganic & medicinal chemistry letters 2005-11, Vol.15 (21), p.4699-4702
• Main Authors: Toyokuni, Tatsushi, Dileep Kumar, J.S., Walsh, Joseph C., Shapiro, Alan, Talley, John J., Phelps, Michael E., Herschman, Harvey R., Barrio, Jorge R., Satyamurthy, Nagichettiar
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Contrast media. Radiopharmaceuticals; COX-2; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - pharmacokinetics; Fluorine Radioisotopes - pharmacokinetics; Fluorine-18; Humans; Inhibitor; Inhibitory Concentration 50; Isoxazoles - chemical synthesis; Macrophages - enzymology; Medical sciences; Mice; PET; Pharmacology. Drug treatments; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Radiotracer; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Tissue Distribution; Valdecoxib
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.07.065

The [ 18F]fluoromethyl analogue of valdecoxib (∼2000 Ci/mmol) was synthesized by [ 18F]fluoride-ion displacement of the corresponding tosylate in ∼40% decay-corrected radiochemical yield within ∼120 min from end of bombardment. 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 (∼2000 Ci/mmol at end of synthesis) was synthesized by [ 18F]fluoride-ion displacement of the corresponding tosylate in ∼40% decay-corrected radiochemical yield within ∼120 min from end of bombardment.