Identification of an active metabolite of PAR-1 antagonist RWJ-58259 and synthesis of analogues to enhance its metabolic stabilityElectronic supplementary information (ESI) available: Full characterisation of all synthesised compounds. See DOI: 10.1039/c6ob00332j

The discontinuation of PAR-1 antagonist RWJ-58259 beyond use as a biological probe is most likely due to it's short half-life in vivo . However, retention of significant in vivo activity beyond the point where most of the RWJ-58259 had been consumed implies the generation of an active metabolit...

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Main Authors Robinson, Eifion, Knight, Emily, Smoktunowicz, Natalia, Chambers, Rachel C, Inglis, Graham G, Chudasama, Vijay, Caddick, Stephen
Format Journal Article
Published 15.03.2016
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Abstract The discontinuation of PAR-1 antagonist RWJ-58259 beyond use as a biological probe is most likely due to it's short half-life in vivo . However, retention of significant in vivo activity beyond the point where most of the RWJ-58259 had been consumed implies the generation of an active metabolite. Herein we describe the biological activity of a predicted metabolite of RWJ-58259 and the synthesis of analogues designed to enhance the metabolic stability of RWJ-58259. Understanding the pharmacokinetic behaviour of PAR-1 antagonist RWJ-58259 and the synthesis of analogues to enhance metabolic stability.
AbstractList The discontinuation of PAR-1 antagonist RWJ-58259 beyond use as a biological probe is most likely due to it's short half-life in vivo . However, retention of significant in vivo activity beyond the point where most of the RWJ-58259 had been consumed implies the generation of an active metabolite. Herein we describe the biological activity of a predicted metabolite of RWJ-58259 and the synthesis of analogues designed to enhance the metabolic stability of RWJ-58259. Understanding the pharmacokinetic behaviour of PAR-1 antagonist RWJ-58259 and the synthesis of analogues to enhance metabolic stability.
Author Robinson, Eifion
Chambers, Rachel C
Smoktunowicz, Natalia
Chudasama, Vijay
Caddick, Stephen
Inglis, Graham G
Knight, Emily
AuthorAffiliation Department of Chemistry
University College London
Centre for Inflammation and Tissue Repair
GSK
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Title Identification of an active metabolite of PAR-1 antagonist RWJ-58259 and synthesis of analogues to enhance its metabolic stabilityElectronic supplementary information (ESI) available: Full characterisation of all synthesised compounds. See DOI: 10.1039/c6ob00332j
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