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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Wang, Cuihua¹  Ashton, Trent D.²  Gustafson, Alden³  Bland, Nicholas D.³  Ochiana, Stefan O.¹  Campbell, Robert K.³  Pollastri, Michael P.¹ 

[1] Northeastern Univ, Dept Chem & Chem Biol, Egan Res Ctr 417, Boston, MA 02115 USA

[2] Boston Univ, Dept Chem, Boston, MA USA

[3] Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA 02543 USA

关键词: Neglected disease;    Trypanosoma brucei;    Target repurposing;    Phosphodiesterase inhibitors;    TbrPDEB1;    PDE5;    Sildenafil;   

DOI  :  10.1016/j.bmcl.2012.01.119

来源: Elsevier

【 摘 要 】

Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and wellbeing 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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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