Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia

Nicholas D Smith; Thomas S Reger; Joseph Payne; Jasmine Zunic; Dan Lorrain; Lucie Correa; Nicholas Stock; Merryl Cramer; Weichao Chen; Jennifer Yang; Peppi Prasit; Benito Munoz

doi:10.1016/j.bmcl.2005.05.002

Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia

Bioorg Med Chem Lett. 2005 Jul 1;15(13):3197-200. doi: 10.1016/j.bmcl.2005.05.002.

Authors

Nicholas D Smith¹, Thomas S Reger, Joseph Payne, Jasmine Zunic, Dan Lorrain, Lucie Correa, Nicholas Stock, Merryl Cramer, Weichao Chen, Jennifer Yang, Peppi Prasit, Benito Munoz

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. [email protected]

PMID: 15936193
DOI: 10.1016/j.bmcl.2005.05.002

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.

MeSH terms

Animals
Blood
Brain
Brain Ischemia / drug therapy*
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / pharmacokinetics*
Cyclooxygenase Inhibitors / pharmacology
Disease Models, Animal
Infusions, Intravenous
Inhibitory Concentration 50
Prodrugs / chemical synthesis*
Prodrugs / pharmacokinetics
Prostaglandin-Endoperoxide Synthases / drug effects*
Rats
Solubility
Tissue Distribution

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Prodrugs
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases