The successful quest for oral factor Xa inhibitors; learnings for all of medicinal chemistry?
The successful quest for oral factor Xa inhibitors; learnings for all of medicinal chemistry?
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DOI：
10.1016/j.bmcl.2011.08.119
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发表时间：
2011-11-01
影响因子：
2.7
通讯作者：
Young, Robert J.
中科院分区：
文献类型：
--
作者：
Young, Robert J.
讨论了口服小分子Xa因子抑制剂的药物化学，突出了导致临床候选药物和第一批许可药物的关键进展。鉴定主要特异性口袋的中性配体是一项关键发现;通过基于结构的设计和组合方法进行资本化，以提供主题的许多变化;但在优化物理性质方面，这是良好的药物化学实践，最终提供了具有足够口服暴露的有效化合物。作为一个回顾性的评估，代表性的化合物进行了分析，使用更现代的配体效率和属性预测指数的概念，这些原则的价值给出了明确的指示。(C)2011爱思唯尔有限公司版权所有。
The medicinal chemistry of oral small molecule factor Xa inhibitors is discussed, highlighting key advances that led to clinical candidates and the first licensed medicines. Identification of neutral ligands for the primary specificity pocket was a key discovery; capitalised upon by structure based design and combinatorial methods to deliver many variations on the theme; but it was good medicinal chemistry practice, in the optimisation of physical properties, which ultimately delivered efficacious compounds with adequate oral exposure. As a retrospective appraisal, representative compounds were profiled using the more contemporary concepts of Ligand Efficiency and Property Forecast Indices; which gave clear indications of the value of these principles. (C) 2011 Elsevier Ltd. All rights reserved.