Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist |
| |
Authors: | Nakamura Akio Yamada Tetsuhiro Asaki Tetsuo |
| |
Institution: | aDiscovery Research Laboratories, Nippon Shinyaku Co., Ltd, 14 Nishinosho-Monguchi-Cho, Kisshoin, Minami-Ku, Kyoto 601 8550, Japan |
| |
Abstract: | 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. |
| |
Keywords: | Prostacyclin IP receptor agonist N-Acylsulfonamide N-Acylsulfonylurea Prodrug |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|