Racemic and chiral sulfoxides as potential prodrugs of 4-pyrone COX-2 inhibitors.
The preparation of the sulfoxide analogues 7, 8, and 9 and their enantiomerically pure forms is discussed as well as their ability to act as prodrugs of the potent and selective sulfone-containing COX-2 inhibitors 1, 2, and 3. Sulfoxide derivatives 7 and 9 were shown to be rapidly transformed in vivo into the corresponding sulfone derivatives 1 and 3, after oral administration to rats.
Caturla
Francisco
F
Department of Medicinal Chemistry, Almirall Prodesfarma S.A., Research Center, Cardener 68-74, 08024 Barcelona, Spain. jfcaturl@almirall.es
Amat
Mercè
M
Reinoso
Raquel F
RF
Calaf
Elena
E
Warrellow
Graham
G
D000818:Animals; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D011355:Prodrugs; D013450:Sulfones; D013454:Sulfoxides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2