Synthesis and biological testing of Acyl-CoA-ketoprofen conjugates as selective irreversible inhibitors of COX-2.

Nicolas Levoin, Françoise Chrétien, Françoise Lapicque, Yves Chapleur

Unité Mixte 7561 CNRS-Université Henri Poincaré-Nancy 1, BP 187, F-54506 Nancy, Vandoeuvre, France.

Bioorganic & medicinal chemistry 2002 Mar

filter terms:

Ketoprofenoyl-CoA thioester 3 was synthesized by coupling ketoprofen to coenzyme A using the mixed anhydride method. Diastereoisomeric compounds 3a and 3b corresponding to the enantiomers of ketoprofen, were obtained in optically pure form by preparative HPLC. A non-acylating analogue, rac-3-(3-benzoylphenyl)-2-oxo-butanoyl-CoA (7) was also prepared. The biological evaluation suggested that 3a and 3b are reversible inhibitors of COX-1 and irreversible inhibitors of COX-2. Compound 7 appears to be a poor but selective inhibitor of COX-1.

Citation

Nicolas Levoin, Françoise Chrétien, Françoise Lapicque, Yves Chapleur. Synthesis and biological testing of Acyl-CoA-ketoprofen conjugates as selective irreversible inhibitors of COX-2. Bioorganic & medicinal chemistry. 2002 Mar;10(3):753-7