title: The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor.
abstract: The activated serine protease factor Xa is a promising target for new anticoagulants. After studies on naturally occurring factor Xa inhibitors indicated that such agents could be effective and safe, research focused on small-molecule direct inhibitors of factor Xa that might address the major clinical need for improved oral anticoagulants. In 2008, rivaroxaban (Xarelto; Bayer HealthCare) became the first such compound to be approved for clinical use. This article presents the history of rivaroxaban's development, from the structure-activity relationship studies that led to its discovery to the preclinical and clinical studies, and also provides a brief overview of other oral anticoagulants in advanced clinical development.
authors.affiliation: Global Therapeutic Research, Pharma R&D, Bayer HealthCare, Wuppertal, Germany. elisabeth.perzborn@bayer.com
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perzborn
authors.forename: Susanne
authors.initials: S
authors.lastname: Roehrig
authors.forename: Alexander
authors.initials: A
authors.lastname: Straub
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kubitza
authors.forename: Frank
authors.initials: F
authors.lastname: Misselwitz
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000069552:Rivaroxaban; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban