Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs
Date
2012-01Metadata
Show full item recordCitable URI
https://hdl.handle.net/1912/5036As published
https://doi.org/10.1016/j.bmcl.2012.01.119Keyword
Neglected disease; Trypanosoma brucei; Target repurposing; Phosphodiesterase inhibitors; TbrPDEB1; PDE5; SildenafilAbstract
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.
Description
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.
Suggested Citation
Preprint: Wang, Cuihua, Ashton, Trent D., Gustafson, Alden, Bland, Nicholas D., Ochiana, Stefan O., Campbell, Robert K., Pollastri, Michael P., "Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs", 2012-01, https://doi.org/10.1016/j.bmcl.2012.01.119, https://hdl.handle.net/1912/5036Related items
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
(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 ... -
Repurposing human PDE4 inhibitors for neglected tropical diseases : design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors
(2014-07)A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the ... -
Xenon hydrate as an analog of methane hydrate in geologic systems out of thermodynamic equilibrium
(American Geophysical Union, 2019-05-06)Methane hydrate occurs naturally under pressure and temperature conditions that are not straightforward to replicate experimentally. Xenon has emerged as an attractive laboratory alternative to methane for studying hydrate ...
