title: Synthesis of novel and potent vorapaxar analogues.
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.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. v.chudasama@ucl.ac.uk s.caddick@ucl.ac.uk.
authors.forename: Emily
authors.initials: E
authors.lastname: Knight
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. v.chudasama@ucl.ac.uk s.caddick@ucl.ac.uk.
authors.forename: Eifion
authors.initials: E
authors.lastname: Robinson
authors.affiliation: Centre for Inflammation and Tissue Repair, 5 University Street, London WC1E 6JJ, UK.
authors.forename: Natalia
authors.initials: N
authors.lastname: Smoktunowicz
authors.affiliation: Centre for Inflammation and Tissue Repair, 5 University Street, London WC1E 6JJ, UK.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Chambers
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. v.chudasama@ucl.ac.uk s.caddick@ucl.ac.uk.
authors.forename: Abil E
authors.initials: AE
authors.lastname: Aliev
authors.affiliation: GSK, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Inglis
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. v.chudasama@ucl.ac.uk s.caddick@ucl.ac.uk.
authors.forename: Vijay
authors.initials: V
authors.lastname: Chudasama
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. v.chudasama@ucl.ac.uk s.caddick@ucl.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Caddick
mesh_terms: D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044463:Receptor, PAR-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D010975:Platelet Aggregation Inhibitors
chemical_list: D007783:Lactones; D011725:Pyridines; D044463:Receptor, PAR-1; C530299:vorapaxar; D010975:Platelet Aggregation Inhibitors