title: Ketomethylureas. A new class of angiotensin converting enzyme inhibitors.
abstract: The design rationale for a new series of tripeptide derived angiotensin converting enzyme (ACE) inhibitors, which we term "ketomethylureas", is described. Analogs of tripeptide substrates (i.e. N-benzoyl-Phe-Ala-Pro) in which the nitrogen atom of the scissile amide bond and the adjacent asymmetric carbon atom of the penultimate amino acid residue are formally transposed give rise to this novel class of inhibitors. The most potent ketomethylureas inhibit ACE with I50 values in the nM range.
authors.affiliation: Squibb Institute for Medical Research, Princeton, New Jersey 08540.
authors.forename: S
authors.initials: S
authors.lastname: Natarajan
authors.forename: E M
authors.initials: EM
authors.lastname: Gordon
authors.forename: E F
authors.initials: EF
authors.lastname: Sabo
authors.forename: J D
authors.initials: JD
authors.lastname: Godfrey
authors.forename: H N
authors.initials: HN
authors.lastname: Weller
authors.forename: J
authors.initials: J
authors.lastname: Pluscec
authors.forename: M B
authors.initials: MB
authors.lastname: Rom
authors.forename: J
authors.initials: J
authors.lastname: Engebrecht
authors.forename: D W
authors.initials: DW
authors.lastname: Cushman
authors.forename: J M
authors.initials: JM
authors.lastname: Deforrest
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D000818:Animals; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008782:Methylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007202:Indicators and Reagents; D007659:Ketones; D008782:Methylurea Compounds; D009842:Oligopeptides