Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs
Date
2012-02-02Metadata
Show full item recordCitable URI
https://hdl.handle.net/1912/5037As published
https://doi.org/10.1016/j.bmcl.2012.01.118Keyword
Neglected disease; Trypanosoma brucei; Target repurposing; Phosphodiesterase inhibitors; TbrPDEB1; PDE5; TadalafilAbstract
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.
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): 2582-2584, doi:10.1016/j.bmcl.2012.01.118.
Suggested Citation
Preprint: Ochiana, Stefan O., Gustafson, Alden, Bland, Nicholas D., Wang, Cuihua, Russo, Michael J., Campbell, Robert K., Pollastri, Michael P., "Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs", 2012-02-02, https://doi.org/10.1016/j.bmcl.2012.01.118, https://hdl.handle.net/1912/5037Related items
Showing items related by title, author, creator and subject.
-
Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs
(2012-01)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. ... -
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 ... -
Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1)
(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 ...
