Abstract
The synthetic design and the biological activities of structurally new angiotensin converting enzyme (ACE) inhibitors, (R)-3-amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine-5-acetic acid derivatives, are described. A number of compounds in this series showed potent ACE inhibitory activity in vitro and in vivo. Structure-activity studies indicated that a piperidyl moiety on the amino group at the 3-position in this series conferred long-lasting ACE inhibitory activity and that the duration of activity depended on the length of the carbon chain in the 1-carboxy-ω-(4-piperidyl)alkyl group. (R)-3-[(S)-1-carboxy-5-(4-piperidyl)-pentyl]amino -4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine-5-acetic acid (CV5975) was selected as the most promising ACE inhibitor for further studies because of its marked inhibitory activity.
