title: Synthesis of human renin inhibitory peptides, angiotensinogen transition-state analogs containing a retro-inverso amide bond.
abstract: The experimental details for the synthesis of human renin inhibitors are described. In order to avoid metabolic degradation of the Phe-His (P3-P2) amide bond in transition-state analogs, structurally modified acyl residues (P4-P3) were incorporated into the inhibitors. Compound 1a, which contained 2-(1-naphthylmethyl)-3-(N-phenethylcarbamoyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and norstatine isoamylamide residue (P1-P1) as a transition-state mimic, had potent human renin inhibitory activity, and it lowered blood pressure when administered orally to common marmosets.
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Iizuka
authors.forename: T
authors.initials: T
authors.lastname: Kamijo
authors.forename: K
authors.initials: K
authors.lastname: Akahane
authors.forename: R
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: A
authors.initials: A
authors.lastname: Tsubaki
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: I
authors.initials: I
authors.lastname: Shimaoka
authors.forename: H
authors.initials: H
authors.lastname: Umeyama
mesh_terms: D000577:Amides; D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000808:Angiotensinogen; D000092502:Renin Inhibitors