Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs

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• 作者：Stefan O. Ochiana^a ; Alden Gustafson^b ; Nicholas D. Bland^b ; Cuihua Wang^a ; Michael J. Russo^a ; Robert K. Campbell^b ; Michael P. Pollastri^a ; ^{m.pollastri@neu.edu}
• 关键词：Neglected disease ; Trypanosoma brucei ; Target repurposing ; Phosphodiesterase inhibitors ; TbrPDEB1 ; PDE5 ; Tadalafil
• 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：2582-2584
• 文件大小：1400 K

摘要

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.