title: The design of potent, selective, non-covalent, peptide thrombin inhibitors utilizing imidazole as a S1 binding element.
abstract: Modeling of neutral or mildly basic functional groups in the S1 site of thrombin led to the targeting of imidazole as a S1 binding element and correctly predicted the optimal chain length for connecting this group with the S2 and S3 binding elements. Derivatives of 4-(3-aminopropyl)-imidazole can be selective inhibitors of thrombin demonstrating potent anticoagulant activity.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Wiley
authors.forename: L C
authors.initials: LC
authors.lastname: Weir
authors.forename: S L
authors.initials: SL
authors.lastname: Briggs
authors.forename: N Y
authors.initials: NY
authors.lastname: Chirgadze
authors.forename: D
authors.initials: D
authors.lastname: Clawson
authors.forename: D S
authors.initials: DS
authors.lastname: Gifford-Moore
authors.forename: A L
authors.initials: AL
authors.lastname: Schacht
authors.forename: G F
authors.initials: GF
authors.lastname: Smith
authors.forename: V
authors.initials: V
authors.lastname: Vasudevan
authors.forename: L L
authors.initials: LL
authors.lastname: Zornes
authors.forename: V J
authors.initials: VJ
authors.lastname: Klimkowski
mesh_terms: D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D007093:Imidazoles; D010455:Peptides