Global Therapeutic Research, Pharma R&D, Bayer HealthCare, Wuppertal, Germany.
Nat Rev Drug Discov. 2011 Jan;10(1):61-75. doi: 10.1038/nrd3185. Epub 2010 Dec 17.
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.
活化的丝氨酸蛋白酶因子 Xa 是新型抗凝剂的一个有前途的靶点。在对天然存在的因子 Xa 抑制剂的研究表明，这些药物可能是有效和安全的之后，研究的重点转向了小分子直接因子 Xa 抑制剂，这可能满足了对改善口服抗凝剂的主要临床需求。2008 年，利伐沙班（拜耳健康护理的拜瑞妥）成为第一个获准临床使用的此类化合物。本文介绍了利伐沙班的开发历史，从导致其发现的构效关系研究到临床前和临床研究，并简要概述了其他处于临床开发后期的口服抗凝剂。
