Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist

N-Acylsulfonamide and N-acylsulfonylurea derivatives of the carboxylic acid prostacyclin receptor agonist 1 were synthesized and their potential as prodrug forms of the carboxylic acid was evaluated in vitro and in vivo. These compounds were converted to the active compound 1 by hepatic microsomes from rats, dogs, monkeys, and humans, and some of the compounds were shown to yield sustained plasma concentrations of 1 when they were orally administered to monkeys. These types of analogues, including NS-304 (2a), are potentially useful prodrugs of 1.

N-Acylsulfonamide and N-acylsulfonylurea derivatives of prostacyclin receptor agonist 1 were evaluated as prodrugs of 1 in vitro and in vivo. These types of analogues, including NS-304 (2a), were found to have potential as new prostacyclin receptor agonist prodrugs with long-lasting activity.Figure optionsDownload as PowerPoint slide