NOVEL RENIN INHIBITORS CONTAINING ,5S)-2-AMINO-1-CYCLOHEXYL-6-METHYL-3,5-HEPTANEDIOL FRAGMENT AS A TRANSITION-STATE MIMIC AT THE P1-P1' CLEAVAGE SITE

Authors
YAMADA Y ANDO K IKEMOTO Y TADA H SHIRAKAWA E INAGAKI E SHIBATA S NAKAMURA I HAYASHI Y IKEGAMI K UCHIDA I
Citation
Y. Yamada et al., NOVEL RENIN INHIBITORS CONTAINING ,5S)-2-AMINO-1-CYCLOHEXYL-6-METHYL-3,5-HEPTANEDIOL FRAGMENT AS A TRANSITION-STATE MIMIC AT THE P1-P1' CLEAVAGE SITE, Chemical and Pharmaceutical Bulletin, 45(10), 1997, pp. 1631-1641
Citations number
32
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
Chemical and Pharmaceutical Bulletin → ACNP
ISSN journal
00092363
Volume
45
Issue
10
Year of publication
1997
Pages
1631 - 1641
Database
ISI
SICI code
0009-2363(1997)45:10<1631:NRIC,>2.0.ZU;2-W
Abstract
A series of renin inhibitors containing the ,5S)-2-amino-1-cyclohexyl- 6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel t ransition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-ami no-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(-10)M rang e, and most of them caused a reduction of blood pressure when administ ered orally to salt-depleted, conscious marmosets, The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the hig hest activity in terms of both potency and duration of the blood press ure-lowering effect.