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

Cuihua Wang, Trent D Ashton, Alden Gustafson, Nicholas D Bland, Stefan O Ochiana, Robert K Campbell, Michael P Pollastri

Bioorganic & medicinal chemistry letters 2012 Apr 01

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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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Cuihua Wang, Trent D Ashton, Alden Gustafson, Nicholas D Bland, Stefan O Ochiana, Robert K Campbell, Michael P Pollastri. Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs. Bioorganic & medicinal chemistry letters. 2012 Apr 01;22(7):2579-81