title: Fused bicyclic Gly-Asp beta-turn mimics with potent affinity for GPIIb-IIIa. Exploration of the arginine isostere.
abstract: 6-[4-Amidinobenzoyl]amino]-tetralone-2-acetic acid is a potent antagonist of GPIIb-IIIa. Substitution in the meta position of the benzamidine, or replacement with a heteroaryl amidine was tolerated in this series. Use of an acyl-linked 4-alkyl piperidine as an arginine isostere also provided active compounds. Compounds from this series provided substantial systemic exposure in the rat following oral administration.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana 46028, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fisher
authors.forename: U
authors.initials: U
authors.lastname: Giese
authors.forename: C S
authors.initials: CS
authors.lastname: Harms
authors.forename: M D
authors.initials: MD
authors.lastname: Kinnick
authors.forename: T D
authors.initials: TD
authors.lastname: Lindstrom
authors.forename: J R
authors.initials: JR
authors.lastname: McCowan
authors.forename: H J
authors.initials: HJ
authors.lastname: Mest
authors.forename: J M
authors.initials: JM
authors.lastname: Morin
authors.forename: J T
authors.initials: JT
authors.lastname: Mullaney
authors.forename: M
authors.initials: M
authors.lastname: Paal
authors.forename: A
authors.initials: A
authors.lastname: Rapp
authors.forename: G
authors.initials: G
authors.lastname: Rühter
authors.forename: K J
authors.initials: KJ
authors.lastname: Ruterbories
authors.forename: D J
authors.initials: DJ
authors.lastname: Sall
authors.forename: R M
authors.initials: RM
authors.lastname: Scarborough
authors.forename: T
authors.initials: T
authors.lastname: Schotten
authors.forename: W
authors.initials: W
authors.lastname: Stenzel
authors.forename: R D
authors.initials: RD
authors.lastname: Towner
authors.forename: S L
authors.initials: SL
authors.lastname: Um
authors.forename: B G
authors.initials: BG
authors.lastname: Utterback
authors.forename: V L
authors.initials: VL
authors.lastname: Wyss
authors.forename: J A
authors.initials: JA
authors.lastname: Jakubowski
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000578:Amidines / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001550:Benzamidines / Q000737:chemistry; D001682:Biological Availability; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D051381:Rats; D013237:Stereoisomerism; D044024:Tetralones
chemical_list: C407727:6-((4-amidinobenzoyl)amino)tetralone-2-acetic acid; D000085:Acetates; D000578:Amidines; D001550:Benzamidines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011355:Prodrugs; D044024:Tetralones; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D001120:Arginine; C032157:benzamidine