Design and campaign synthesis of pyridine-based histone deacetylase inhibitors
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- 作者：David M. Andrews ; Keith M. Gibson ; Mark A. Graham ; Zbigniew S. Matusiak ; Craig A. Roberts ; Elaine S.E. Stokes ; Madeleine C. Brady ; Christine M. Chresta
- 关键词：HDAC ; Histone ; Deacetylase ; HCT-116 ; Benzamide
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：15 April 2008
- 年：2008
- 卷：18
- 期：8
- 页码：2525-2529
- 全文大小：140 K
文摘
A lead benzamide, bearing a cyanopyridyl moiety (3), was identified as a potent and low molecular weight histone deacetylase (HDAC) inhibitor. Various replacements of the cyano group were explored at the C3-position, along with the exploration of solubility-enhancing groups at the C5-position. It was determined that cyano substitution at the C3-position of the pyridyl core, along with a methylazetidinyl substituent at the C5-position yielded optimal HDAC1 inhibition and anti-proliferative activity in HCT-116 cells.