Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privileged structure that engenders PLD2 selectivity

详细信息    查看全文

• 作者：Robert Lavieri ; Sarah A. Scott ; Jana A. Lewis ; Paige E. Selvy ; Michelle D. Armstrong ; H. Alex Brown ; Craig W. Lindsley
• 关键词：PLD ; Phospholipase ; Cancer ; Privileged structure
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 April 2009
• 年：2009
• 卷：19
• 期：8
• 页码：2240-2243
• 全文大小：541 K

文摘

This Letter describes the synthesis and structure–activity relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of a 1,3,8-triazaspiro[4,5]decan-4-one privileged structure, PLD inhibitors with nanomolar potency and an unprecedented 40-fold selectivity for PLD2 over PLD1 were developed. Interestingly, SAR for this diverged from our earlier efforts, and dual PLD1/2 inhibitors were also discovered within this series.