4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors

Eur J Med Chem. 2014 Apr 9:76:53-60. doi: 10.1016/j.ejmech.2014.01.056. Epub 2014 Jan 30.


Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]-pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6.

Keywords: 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines; Anti-cancer drugs; Heat shock protein 90.

MeSH terms

  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Flow Cytometry
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • K562 Cells
  • Magnetic Resonance Spectroscopy
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization


  • HSP90 Heat-Shock Proteins
  • Pyridines