Abstract
Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / chemical synthesis
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Adenosine / chemistry
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Adenosine / pharmacology
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Adenosine Diphosphate / pharmacology
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Animals
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Blood Platelets / drug effects*
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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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Purinergic P2Y Receptor Antagonists / chemical synthesis*
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Purinergic P2Y Receptor Antagonists / chemistry
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Purinergic P2Y Receptor Antagonists / pharmacology
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Rats
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Receptors, Purinergic P2Y12 / chemistry*
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Receptors, Purinergic P2Y12 / metabolism
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Structure-Activity Relationship
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Ticagrelor
Substances
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Platelet Aggregation Inhibitors
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Purinergic P2Y Receptor Antagonists
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Receptors, Purinergic P2Y12
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Adenosine Diphosphate
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Ticagrelor
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Adenosine