Titre du document / Document title

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

Auteur(s) / Author(s)

PRABHAKARAN Jaya ⁽¹⁾ ; MAJO Vattoly J. ⁽¹⁾ ; SIMPSON Norman R. ^{(2 3)} ; VAN HEERTUM Ronald L. ⁽³⁾ ; MANN J. John ^{(1 2 3)} ; DILEEP KUMAR J. S. ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Psychiatry, Columbia University, New York, NY 10032, ETATS-UNIS
⁽²⁾ Division of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, ETATS-UNIS
⁽³⁾ Department of Radiology, Columbia University, New York, NY 10032, ETATS-UNIS

Résumé / Abstract

[¹¹C]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)-3-trifluoromethylpyrazol-1-yl]benzenesulfonamide (5) with methyl iodide in presence of catalytic amounts of Pd₂(dba)₃, tri-o-tolylphosphine, CuCl and excess of K₂CO₃ in DMF followed by deprotection of the sulfonamide with 20% trifluoroaceticacid yielded 4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide or celecoxib (6) in 30% yield. However, under identical conditions, synthesis of [¹¹C]celecoxib ([C]6) was unsuccessful. Instead, trapping [¹¹C]CH₃I in an argon purged solution of catalytic amounts of Pd₂(dba)₃ and tri-o-tolylphosphine followed by the addition of the precursor 5 in DMF under argon and heating the mixture at 135°C for 4min resulted in the incorporation of [¹¹C]CH₃ group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [C]celecoxib in 40min (EOB) and 8 ± 2% yield (EOB) along with a specific activity of 1080 ± 180Ci/mmol (n = 6) (EOB).

Revue / Journal Title

Journal of labelled compounds & radiopharmaceuticals   ISSN 0362-4803 

Source / Source

2005, vol. 48, n^o12, pp. 887-895 [9 page(s) (article)] (24 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley, Chichester, ROYAUME-UNI  (1976) (Revue)

Mots-clés anglais / English Keywords

Pyrazole derivatives ; Sulfonamide ; Prostaglandin-endoperoxide synthase ; Enzyme inhibitor ; Cyclooxygenase 2 inhibitor ; Enzyme ; Oxidoreductases ; Carbon Isotopes ; Iodomethane ; Scintigraphic agent ; Non steroidal antiinflammatory agent ; Cyclooxygenase 2 ; Celecoxib ; Carbon 11 ; Chemical synthesis ;

Mots-clés français / French Keywords

Pyrazole dérivé ; Sulfonamide ; Prostaglandin-endoperoxide synthase ; Inhibiteur enzyme ; Inhibiteur cyclooxygenase 2 ; Enzyme ; Oxidoreductases ; Acétophénone(4-bromo) ; Carbone Isotope ; Méthane(iodo) ; Agent scintigraphique ; Antiinflammatoire non stéroïde ; Cyclooxygenase 2 ; Célécoxib ; Carbone 11 ; Synthèse chimique ;

Mots-clés espagnols / Spanish Keywords

Pirazol derivado ; Sulfonamida ; Prostaglandin-endoperoxide synthase ; Inhibidor enzima ; Inhibidor cyclooxygenase 2 ; Enzima ; Oxidoreductases ; Carbono Isótopo ; Metano(iodo) ; Agente centelleográfico ; Antiinflamatorio no esteroide ; Cyclooxygenase 2 ; Celecoxib ; Síntesis química ;

Mots-clés d'auteur / Author Keywords

celecoxib ; COX-2 expression ; prostaglandins ; NSAIDs ; PET ligand ;

Localisation / Location

INIST-CNRS, Cote INIST : 12609, 35400013252656.0030