title: Synthesis and stability study of a modified phenylpropionic acid linker-based esterase-sensitive prodrug.
abstract: An esterase-sensitive amide prodrug 1 with a modified phenylpropionic acid linker was synthesized. The prodrug can be converted to the drug using isolated porcine esterase and human plasma. Paraoxon, an esterase inhibitor, can inhibit prodrug-to-drug conversion. The conversion of prodrug 1 was via phenol intermediate 9 followed by a lactonization reaction to give lactone 2 and the drug.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Song
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004355:Drug Stability; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007783:Lactones / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D010261:Paraoxon / Q000494:pharmacology; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013379:Substrate Specificity; D013552:Swine; D013997:Time Factors
chemical_list: D000577:Amides; D002800:Cholinesterase Inhibitors; D007783:Lactones; D010666:Phenylpropionates; D011355:Prodrugs; D004950:Esterases; D010261:Paraoxon