The 2010 Patent Landscape for Spleen Tyrosine Kinase Inhibitors
The 2010 Patent Landscape for Spleen Tyrosine Kinase Inhibitors
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DOI：
10.2174/187221312800166895
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Thorarensen, Atli
中科院分区：
文献类型：
--
作者：
Moretto, Alessandro F.;Dehnhardt, Christoph;Thorarensen, Atli
用于治疗类风湿性关节炎的小分子抑制剂的发现是制药行业内的主要持续努力。脾酪氨酸激酶（SYK）是临床开发的主要小分子靶点之一，主要是由于Rigel和Portola的努力。在本文中，我们对SYK专利格局进行了全面概述。我们评估的专利文献涉及任何已提交申请的组织，这些申请暗示SYK是预期目标。对SYK的兴趣始于21世纪初，许多组织，包括几家大型制药公司，多年来一直很活跃。通常，这些应用中的大多数化合物的结构主题是传统的ATP竞争性抑制剂，其中每个组织具有不同的铰链结合元件。通常，与铰链的连接是用增溶基团修饰的芳基胺。其他取代基在许多公司中变化很大，表明SYK在激酶的该部分中的相互作用具有显著的灵活性。SYK专利文献的概述和对抑制剂取代模式的了解将是该领域工作人员的重要参考。
Discovery of small molecular inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of leading small molecular targets with regard to clinical development primarlly due to efforts by Rigel and Portola. In this review, we provide a comprehensive overview of the SYK patent landscape. The patent literature we evaluated relates to any organization that has filed applications that imply that SYK is the intended target. The interest in SYK was initiated in the early 2000's with many organizations, including several large pharmaceutical companies, and has been active for years. In general, the structural theme of most of the compounds in these applications is a traditional ATP competitive inhibitor with each organization having a different hinge binding element. In general, the attachment to the hinge is an aryl amine that is decorated with a solubilizing group. The other substituents are broadly variable across the numerous companies indicating that SYK has significant flexibility in its interactions in that portion of the kinase. This overview of the SYK patent literature and the learnings of the inhibitors' substitution patterns would be an important reference for anyone working in this area.