Synthesis, characterization, and activity of metabolites derived from the cyclooxygenase-2 inhibitor rofecoxib (MK-0966, Vioxx).
Metabolites of the COX-2 inhibitor rofecoxib (MK-0966, Vioxx) were prepared by synthetic or biosynthetic methods. Metabolites include products of oxidation, glucuronidation, reduction and hydrolytic ring opening. Based on an in vitro whole blood assay, none of the known human metabolites of rofecoxib inhibits COX-1 nor contributes significantly to the inhibition of COX-2.
Nicoll-Griffith
D A
DA
Merck Frosst Centre for Therapeutic Research, Pointe-Claire-Dorval, Québec, Canada. deborah_nicoll_griffith@merck.com
Yergey
J A
JA
Trimble
L A
LA
Silva
J M
JM
Li
C
C
Chauret
N
N
Gauthier
J Y
JY
Grimm
E
E
Léger
S
S
Roy
P
P
Thérien
M
M
Wang
Z
Z
Prasit
P
P
Zamboni
R
R
Young
R N
RN
Brideau
C
C
Chan
C C
CC
Mancini
J
J
Riendeau
D
D
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D051381:Rats; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat