Synthesis and stability study of a modified phenylpropionic acid linker-based esterase-sensitive prodrug

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. (C) 2002 Elsevier Science Ltd. All rights reserved.