Identification of an active metabolite of PAR-1 antagonist RWJ-58259 and synthesis of analogues to enhance its metabolic stability. Issue 12 (1st March 2016)

• Record Type: Journal Article
• Authors: Robinson, Eifion; Knight, Emily; Smoktunowicz, Natalia; Chambers, Rachel C.; Inglis, Graham G.; Chudasama, Vijay; Caddick, Stephen
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 12(2016)
• Page Start: 3198
• Page End: 3201
• Publication Date: 2016-03-01
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob00332j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Understanding the pharmacokinetic behaviour of PAR-1 antagonist RWJ-58259 and the synthesis of analogues to enhance metabolic stability. 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.