Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs
Ashton, Trent D.
Bland, Nicholas D.
Ochiana, Stefan O.
Campbell, Robert K.
Pollastri, Michael P.
MetadataShow full item record
KeywordNeglected disease; Trypanosoma brucei; Target repurposing; Phosphodiesterase inhibitors; TbrPDEB1; PDE5; Sildenafil
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.
Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Bioorganic & Medicinal Chemistry Letters 22 (2012): 2579-2581, doi:10.1016/j.bmcl.2012.01.119.
Showing items related by title, author, creator and subject.
Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs Ochiana, Stefan O.; Gustafson, Alden; Bland, Nicholas D.; Wang, Cuihua; Russo, Michael J.; Campbell, Robert K.; Pollastri, Michael P. (2012-02-02)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 ...
Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1) Woodring, Jennifer L.; Bland, Nicholas D.; Ochiana, Stefan O.; Campbell, Robert K.; Pollastri, Michael P. (2013-08-07)Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our ...
Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1) Amata, Emanuele; Bland, Nicholas D.; Campbell, Robert K.; Pollastri, Michael P. (2015-04-13)Human African trypanosomiasis (HAT) is a parasitic disease, caused by the protozoan pathogen Trypanosoma brucei, which affects thousands every year and which is in need of new therapeutics. Herein we report the synthesis ...