New patented histone deacetylase inhibitors

Expert Opinion on Therapeutic Patents
Haishan Wang, Brian W Dymock

Abstract

Following FDA approval of vorinostat in 2006, several novel HDAC inhibitors (HDACis) have entered clinical trials, and there are numerous published patent applications claiming novel HDACis which were optimized as potential drug candidates, designed for regional or systemic release, and created as dual or multifunctional inhibitors. Given the breadth and depth of recent reporting of novel HDACis, there has emerged a need to review the field from a chemist's perspective in one compact article. This review provides a summary of published patent applications claiming novel HDACis from 2007 until mid-2009, covering mainly classes I, II and IV anticancer HDACis including those that have recently advanced to the clinic. Readers will rapidly gain an overview of the majority of HDACi scaffolds with representative structure-activity relationships; they will learn how these new compounds were created, how their drug like properties were improved and which companies are the main players in the field. Although competition in this field is intense, the future application of HDACis to treat human disease either as single agents or in combination with existing drugs holds real promise.

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