Abstract
The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)β(3) integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Arginine / analogs & derivatives
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Arginine / metabolism
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Blood Platelets / metabolism
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Drug Design*
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Drug Evaluation, Preclinical
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Fibrinogen / metabolism
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Fluorescein-5-isothiocyanate / metabolism
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Humans
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Isoquinolines / chemistry
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Isoquinolines / metabolism
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Ligands
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Oligopeptides / chemistry
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Oligopeptides / metabolism
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Phthalimides / chemical synthesis*
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Platelet Aggregation Inhibitors / chemical synthesis*
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology*
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
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Protein Binding
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Receptors, Fibrinogen / antagonists & inhibitors*
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Receptors, Fibrinogen / metabolism
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Software
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Stereoisomerism
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Structure-Activity Relationship
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Tirofiban
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Tyrosine / analogs & derivatives
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Tyrosine / chemistry
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Tyrosine / metabolism
Substances
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Isoquinolines
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Ligands
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Oligopeptides
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Phthalimides
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Platelet Aggregation Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex
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Receptors, Fibrinogen
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Tyrosine
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arginyl-glycyl-aspartic acid
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Fibrinogen
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Arginine
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Tirofiban
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Fluorescein-5-isothiocyanate
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isoquinoline