Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2582-4. doi: 10.1016/j.bmcl.2012.01.118. Epub 2012 Feb 9.

Abstract

In this Letter 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Carbolines / chemical synthesis*
  • Carbolines / chemistry
  • Humans
  • Phosphodiesterase 5 Inhibitors / chemical synthesis*
  • Phosphodiesterase 5 Inhibitors / chemistry
  • Phosphoric Diester Hydrolases / chemistry*
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / chemistry
  • Solutions
  • Structure-Activity Relationship
  • Tadalafil
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Carbolines
  • Phosphodiesterase 5 Inhibitors
  • Protozoan Proteins
  • Solutions
  • Trypanocidal Agents
  • Tadalafil
  • Phosphoric Diester Hydrolases