Synthesis of [11C]celecoxib: a potential PET probe for imaging COX-2 expression

✍ Scribed by Jaya Prabhakaran; Vattoly J. Majo; Norman R. Simpson; Ronald L. Van Heertum; J. John Mann; J. S. Dileep Kumar

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 121 KB
• Volume: 48
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1002

✦ Synopsis

11 C]Labeling of celecoxib, a COX-2 selective inhibitor and prescription drug for arthritis and pain has been achieved. The precursor molecule for the radiolabeling was synthesized from 4-bromoacetophenone in 4 steps with 23% overall yield. Stille reaction of N-[bis-(4-methoxyphenyl)phenylmethyl]-4-[5-(4-tributylstannylphenyl)-3trifluoromethylpyrazol-1-yl]benzenesulfonamide ð5Þ with methyl iodide in presence of catalytic amounts of Pd 2 (dba) 3 , tri-o-tolylphosphine, CuCl and excess of K 2 CO 3 in DMF followed by deprotection of the sulfonamide with 20% trifluoroaceticacid yielded 4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide or celecoxib ð6Þ in 30% yield. However, under identical conditions, synthesis of [ 11 C]celecoxib ([ 11 C]6) was unsuccessful. Instead, trapping [ 11 C]CH 3 I in an argon purged solution of catalytic amounts of Pd 2 (dba) 3 and tri-o-tolylphosphine followed by the addition of the precursor 5 in DMF under argon and heating the mixture at 1358C for 4 min resulted in the incorporation of [ 11 C]CH 3 group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [ 11 C]celecoxib in 40 min (EOB) and 8 AE 2% yield (EOB) along with a specific activity of 1080 AE 180 Ci/mmol ðn ¼ 6Þ (EOB).