title: Slow, tight binding to human renin of some nonpeptidic renin inhibitors containing a 4-methoxymethoxypiperidinylamide at the P4 position.
abstract: A series of nonpeptidic human renin inhibitors with a 4-methoxymethoxypiperidinylamide at the P4 position of the molecule exhibited slow tight binding to the enzyme. Replacement of the methoxymethoxy moiety on the piperidine ring with H, OH, methoxyethyl, propyloxy or n-butyl eliminated the effect. The inhibition was partially reversed by prolonged dialysis at 4 degrees C, arguing against formation of a covalent bond in the tightened complex.
authors.affiliation: Abbott Laboratories, Cardiovascular Research Division, Abbott Park, Illinois 60064.
authors.forename: H H
authors.initials: HH
authors.lastname: Stein
authors.forename: A K
authors.initials: AK
authors.lastname: Fung
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: W R
authors.initials: WR
authors.lastname: Baker
authors.forename: S H
authors.initials: SH
authors.lastname: Rosenberg
authors.forename: S A
authors.initials: SA
authors.lastname: Boyd
authors.forename: B D
authors.initials: BD
authors.lastname: Dayton
authors.forename: Y L
authors.initials: YL
authors.lastname: Armiger
authors.forename: S L
authors.initials: SL
authors.lastname: Condon
authors.forename: R A
authors.initials: RA
authors.lastname: Mantei
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation; D006801:Humans; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D012083:Renin / Q000097:blood / Q000737:chemistry; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D010880:Piperidines; D012083:Renin; D000092502:Renin Inhibitors; C032727:piperidine