New substrate analogue furin inhibitors derived from 4-amidinobenzylamide

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 16; pp. 4695 - 4697
• Main Authors: Becker, Gero L., Hardes, Kornelia, Steinmetzer, Torsten
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.08.2011; Elsevier
• Subjects: Amidines - chemical synthesis; Amidines - chemistry; Amidines - pharmacology; amino acids; Analytical, structural and metabolic biochemistry; Benzyl Compounds - chemical synthesis; Benzyl Compounds - chemistry; Benzyl Compounds - pharmacology; Biological and medical sciences; cell culture; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Furin; Furin - antagonists & inhibitors; Hydrolases; Medical sciences; Miscellaneous; Molecular Conformation; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptidomimetic inhibitor; Peptidomimetics - chemical synthesis; Peptidomimetics - chemistry; Peptidomimetics - pharmacology; Pharmacology. Drug treatments; Proprotein convertase; Protease inhibitor; proteinase inhibitors; Serine protease; Structure-Activity Relationship; Furin; Serine protease; Peptidomimetic inhibitor; Proprotein convertase; Protease inhibitor; Serine endopeptidases; Peptides; Enzyme; Peptidomimetic compound; Tripeptide; Enzyme inhibitor; Guanidines; In vitro; Peptidases; Amidine; Structure activity relation; Hydrolases; Peptide synthesis; Solid phase; Valine derivatives

A series of new peptidomimetic furin inhibitors was synthesized, which was derived from our previously described lead structure phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide (1). Substitution of Val by other amino acid residues revealed several highly potent furin inhibitors with Ki values of less t...