Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs

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• 作者：Cuihua Wang^a ; Trent D. Ashton^b ; Alden Gustafson^c ; Nicholas D. Bland^c ; Stefan O. Ochiana^a ; Robert K. Campbell^c ; Michael P. Pollastri^a ; ^{m.pollastri@neu.edu}
• 关键词：Neglected disease ; Trypanosoma brucei ; Target repurposing ; Phosphodiesterase inhibitors ; TbrPDEB1 ; PDE5 ; Sildenafil
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 April, 2012
• 卷：22
• 期：7
• 页码：2579-2581
• 文件大小：554 K

摘要

Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.