title: Novel approach to pro-drugs of lactones: water soluble imidate and ortho-ester derivatives of a furanone-based COX-2 selective inhibitor.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. steve_poon@merck.com
authors.forename: Steve F
authors.initials: SF
authors.lastname: Poon
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Payne
authors.forename: Angela R
authors.initials: AR
authors.lastname: McGuire
authors.forename: Brian
authors.initials: B
authors.lastname: Stearns
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
authors.forename: Weichao
authors.initials: W
authors.lastname: Chen
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Smith
mesh_terms: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004952:Esters; D005663:Furans; D007094:Imides; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012995:Solubility
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004952:Esters; D005663:Furans; D007094:Imides; D007202:Indicators and Reagents; D007783:Lactones; D011355:Prodrugs; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases