title: Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. Nicholas_Smith@merck.com
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Smith
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Reger
authors.forename: Joseph
authors.initials: J
authors.lastname: Payne
authors.forename: Jasmine
authors.initials: J
authors.lastname: Zunic
authors.forename: Dan
authors.initials: D
authors.lastname: Lorrain
authors.forename: Lucie
authors.initials: L
authors.lastname: Correa
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
authors.forename: Merryl
authors.initials: M
authors.lastname: Cramer
authors.forename: Weichao
authors.initials: W
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yang
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
mesh_terms: 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
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases