Synthesis of novel and potent vorapaxar analogues. Issue 12 (2nd March 2016)

• Record Type: Journal Article
• Authors: Knight, Emily; Robinson, Eifion; Smoktunowicz, Natalia; Chambers, Rachel C.; Aliev, Abil E.; Inglis, Graham G.; Chudasama, Vijay; Caddick, Stephen
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 12(2016)
• Page Start: 3264
• Page End: 3274
• Publication Date: 2016-03-02
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob02541a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Unlocking novel and potent vorapaxar analogues by functionalisation of previously unexplored positions on the parent vorapaxar scaffold. Abstract : Vorapaxar is a first-in-class PAR-1 antagonistic drug based on the ent -himbacine scaffold. Detailed in this article are enantioselective and racemic routes to various novel vorapaxar analogues. Biological testing revealed these compounds to have moderate to excellent potencies against PAR-1 with the most potent analogue demonstrating an IC50 of 27 nM.