- 著者
- Yasuki YAMADA Koji ANDO Yukishige IKEMOTO Hiroki TADA Eiji SHIRAKAWA Eiji INAGAKI Saizo SHIBATA Ikuro NAKAMURA Yoshiharu HAYASHI Kiyoteru IKEGAMI Itsuo UCHIDA
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.45, no.10, pp.1631-1641, 1997-10-15 (Released:2008-03-31)
- 参考文献数
- 32
- 被引用文献数
- 4 4
A series of renin inhibitors containing the (2S, 3S, 5S)-2-amino-1-cyclohexyl-6-methyl-3, 5-heptanediol (2-amino-3, 5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3, 5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10-8-10-10M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.