title: The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs.
abstract: The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies.
authors.affiliation: GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Watson
authors.forename: Carl
authors.initials: C
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Belton
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Burns-Kurtis
authors.forename: Laiq
authors.initials: L
authors.lastname: Chaudry
authors.forename: Chuen
authors.initials: C
authors.lastname: Chan
authors.forename: Máire A
authors.initials: MA
authors.lastname: Convery
authors.forename: David E
authors.initials: DE
authors.lastname: Davies
authors.forename: Anne M
authors.initials: AM
authors.lastname: Exall
authors.forename: John D
authors.initials: JD
authors.lastname: Harling
authors.forename: Stephanie
authors.initials: S
authors.lastname: Irvine
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Irving
authors.forename: Savvas
authors.initials: S
authors.lastname: Kleanthous
authors.forename: Iain M
authors.initials: IM
authors.lastname: McLay
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Pateman
authors.forename: Angela N
authors.initials: AN
authors.lastname: Patikis
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Roethke
authors.forename: Stefan
authors.initials: S
authors.lastname: Senger
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Stelman
authors.forename: John R
authors.initials: JR
authors.lastname: Toomey
authors.forename: Robert I
authors.initials: RI
authors.lastname: West
authors.forename: Caroline
authors.initials: C
authors.lastname: Whittaker
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Young
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors; D015394:Molecular Structure; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors; D044005:Tetrahydroisoquinolines