Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia.
A water soluble choline prodrug (17) of a COX-2 selective inhibitor (16) suitable for intravenous dosing in models of cerebral ischemia has been developed. Constant infusion studies using 17 demonstrate that extrapolated brain levels of 16 may be maintained for over 24h in rats.
Smith
Nicholas D
ND
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. Nicholas_Smith@merck.com
Reger
Thomas S
TS
Payne
Joseph
J
Zunic
Jasmine
J
Lorrain
Dan
D
Correa
Lucie
L
Stock
Nicholas
N
Cramer
Merryl
M
Chen
Weichao
W
Yang
Jennifer
J
Prasit
Peppi
P
Munoz
Benito
B
D000818:Animals; D001769:Blood; D001921:Brain; D002545:Brain Ischemia / Q000188:drug therapy*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D020128:Inhibitory Concentration 50; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D051381:Rats; D012995:Solubility; D014018:Tissue Distribution
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases