title: Renin inhibitors. I. Synthesis and structure-activity relationships of transition-state inhibitors containing homostatine analogues at the scissile bond.
abstract: 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.
authors.affiliation: Chemistry of Natural Products, Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Atsuumi
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: Y
authors.initials: Y
authors.lastname: Koike
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Matsuyama
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: H
authors.initials: H
authors.lastname: Morishima
mesh_terms: D006801:Humans; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000092502:Renin Inhibitors