Novel approach to pro-drugs of lactones: water soluble imidate and ortho-ester derivatives of a furanone-based COX-2 selective inhibitor.
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.
Poon
Steve F
SF
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. steve_poon@merck.com
Stock
Nicholas
N
Payne
Joseph E
JE
McGuire
Angela R
AR
Stearns
Brian
B
Yang
Xiaoqing
X
Chen
Weichao
W
Munoz
Benito
B
Smith
Nicholas D
ND
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
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