(R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5- tetrahydro-1,5-benzothiazepine-5-acetic acid (CV-5975): a new potent and long-lasting inhibitor of angiotensin converting enzyme.
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-omega-(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 (CV-5975) was selected as the most promising ACE inhibitor for further studies because of its marked inhibitory activity.
Inada
Y
Y
Biology Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Itoh
K
K
Kamiya
K
K
Sugihara
H
H
Nishikawa
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000493:pharmacokinetics / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; C054055:CV 5975