Novel approach to pro-drugs of lactones: water soluble imidate and ortho-ester derivatives of a furanone-based COX-2 selective inhibitor

Steve F Poon; Nicholas Stock; Joseph E Payne; Angela R McGuire; Brian Stearns; Xiaoqing Yang; Weichao Chen; Benito Munoz; Nicholas D Smith

doi:10.1016/j.bmcl.2005.03.009

Novel approach to pro-drugs of lactones: water soluble imidate and ortho-ester derivatives of a furanone-based COX-2 selective inhibitor

Bioorg Med Chem Lett. 2005 May 2;15(9):2259-63. doi: 10.1016/j.bmcl.2005.03.009.

Authors

Steve F Poon¹, Nicholas Stock, Joseph E Payne, Angela R McGuire, Brian Stearns, Xiaoqing Yang, Weichao Chen, Benito Munoz, Nicholas D Smith

Affiliation

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

PMID: 15837305
DOI: 10.1016/j.bmcl.2005.03.009

Abstract

Interest in water soluble COX-2 inhibitors that can be administered intravenously led to the development of novel pro-drugs of a furanone based COX-2 inhibitor 2. Transforming the lactone moiety of the furanone to an imidate or an ortho-ester with a hydrophilic, endogenous appendage resulted in water soluble pro-drugs that converted to the parent drug in vivo.

MeSH terms

Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology
Esters
Furans
Imides
Indicators and Reagents
Lactones / chemical synthesis*
Lactones / chemistry
Lactones / pharmacology
Models, Molecular
Molecular Structure
Prodrugs / chemical synthesis*
Prodrugs / chemistry
Prodrugs / pharmacology
Prostaglandin-Endoperoxide Synthases / metabolism*
Solubility

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Esters
Furans
Imides
Indicators and Reagents
Lactones
Prodrugs
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases