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Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 1. Sildenafil Analogs, 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. 1. Sildenafil Analogs, Cuihua Wang, Trent D. Ashton, Alden Gustafson, Nicholas D. Bland, Stefan O. Ochiana, Robert K. Campbell, Michael P. Pollastri
Michael Pollastri
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 report 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.
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 2. Tadalafil Analogs, Stefan O. Ochiana, Alden Gustafson, Nicholas D. Bland, Cuihua Wang, Michael J. Russo, Robert K. Campbell, Michael P. Pollastri
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 2. Tadalafil Analogs, Stefan O. Ochiana, Alden Gustafson, Nicholas D. Bland, Cuihua Wang, Michael J. Russo, Robert K. Campbell, Michael P. Pollastri
Michael Pollastri
In this report 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.