Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist
Synthesis and evaluation of N-acylsulfonamide and N-acylsulfonylurea prodrugs of a prostacyclin receptor agonist
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DOI：
10.1016/j.bmc.2007.08.052
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发表时间：
2007-12-15
影响因子：
3.5
通讯作者：
Asaki, Tetsuo
中科院分区：
文献类型：
--
作者：
Nakamura, Akio;Yamada, Tetsuhiro;Asaki, Tetsuo
合成了羧酸前列环素受体激动剂1的N-酰基磺酰胺和N-酰基磺酰脲衍生物，并在体外和体内评价了它们作为羧酸前药形式的潜力。这些化合物通过大鼠、狗、猴子和人类的肝微粒体转化为活性化合物 1，其中一些化合物在给猴子口服时显示出持续的血浆浓度 1。这些类型的类似物，包括 NS-304 (2a)，是 1 的潜在有用的前药。(c) 2007 Elsevier Ltd. 保留所有权利。
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. (c) 2007 Elsevier Ltd. All rights reserved.