Renin inhibitors. I. Synthesis and structure-activity relationships of transition-state inhibitors containing homostatine analogues at the scissile bond.
The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3-hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result suggests that S1, S3 and S4 form a huge hydrophobic core together in renin.
Atsuumi
S
S
Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Nakano
M
M
Koike
Y
Y
Tanaka
S
S
Matsuyama
K
K
Nakano
M
M
Morishima
H
H
D006801:Humans; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000092502:Renin Inhibitors