title: New renin inhibitors--stability and activity determination. Part I.
abstract: A series of new six potential renin inhibitors containing pseudodipeptides were synthesized. Stability for all compounds (1-6) in homogenates of liver, kidney, lung and in serum, gastric, intestinal juice and in the presence of alpha-chymotrypsin was determined. Compound 5 was unstable, compound 6 was stable, other compounds were partly unstable, compound 2 was stable except kidney homogenate and compound 4 was stable except liver homogenate. Inhibitory activity of the compounds was measured in vitro by HPLC determination of lowering concentration of substrate (angiotensinogen) in the presence of renin and the potential renin inhibitor (compounds 1-6). Compound 2, 4 and 6 showed inhibitory activity (1.4 x 10(-6), 5.2 x 10(-6), 1.5 x 10(-7) M, respectively). Other compounds (1, 3, 5) showed no inhibitory activity up to 10(-5) M.
authors.forename: Dorota
authors.initials: D
authors.lastname: Marszałek
authors.forename: Anna
authors.initials: A
authors.lastname: Goldnik
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
authors.forename: Iwona
authors.initials: I
authors.lastname: Winiecka
authors.forename: Paweł
authors.initials: P
authors.lastname: Jaworskpi
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000494:pharmacology; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D000092502:Renin Inhibitors
chemical_list: D002918:Chymotrypsin; D004791:Enzyme Inhibitors; D000092502:Renin Inhibitors; C117608:alpha-chymotrypsin