New approaches to the synthesis of sildenafil analogues and their enzyme inhibitory activity

Bioorg Med Chem. 2015 Apr 1;23(7):1421-9. doi: 10.1016/j.bmc.2015.02.026. Epub 2015 Feb 21.

Abstract

In the search for new biologically active chemotypes, several sildenafil analogs were prepared and characterized. The presence of the pyrazolo[4,3-e][1,2,4]triazine core is thought to be of interest for the enzyme inhibitory activity of these compounds. The designed derivatives incorporating the sildenafil scaffold were assayed as carbonic anhydrase inhibitors, and for their cytotoxic activity against MCF-7 and K562 cell lines. The X-ray analysis of one of these model compounds was performed and its crystal structure is described/compared to that of sildenafil.

Keywords: DFT calculations; Pyrazolo[4,3-e][1,2,4]triazine; Sildenafil analogues; Sulfonamides; X-ray structure analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Humans
  • K562 Cells
  • MCF-7 Cells
  • Phosphodiesterase 5 Inhibitors / chemical synthesis
  • Sildenafil Citrate / analogs & derivatives*
  • Sildenafil Citrate / chemical synthesis*

Substances

  • Enzyme Inhibitors
  • Phosphodiesterase 5 Inhibitors
  • Sildenafil Citrate