Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system xc- transporter: Initial homology model

Bioorg Med Chem Lett. 2013 Nov 1;23(21):5931-5. doi: 10.1016/j.bmcl.2013.08.080. Epub 2013 Aug 27.

Abstract

Microwave accelerated reaction system (MARS) technology provided a good method to obtain selective and open isoxazole ligands that bind to and inhibit the Sxc- antiporter. The MARS provided numerous advantages, including: shorter time, better yield and higher purity of the product. Of the newly synthesized series of isoxazoles the salicyl hydrazide 6 exhibited the highest level of inhibitory activity in the transport assay. A homology model has been developed to summarize the SAR results to date, and provide a working hypothesis for future studies.

Keywords: Cystine; Glutamate; Isoxazole; Microwave; Transporter.

Publication types

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

MeSH terms

  • Amino Acid Transport System y+ / antagonists & inhibitors*
  • Amino Acid Transport System y+ / chemistry
  • Amino Acid Transport System y+ / metabolism
  • Cell Line
  • Cystine / metabolism
  • Glutamic Acid / metabolism
  • Humans
  • Isoxazoles / chemical synthesis
  • Isoxazoles / chemistry*
  • Isoxazoles / pharmacology*
  • Microwaves
  • Molecular Docking Simulation
  • Structural Homology, Protein

Substances

  • Amino Acid Transport System y+
  • Isoxazoles
  • SLC7A11 protein, human
  • Glutamic Acid
  • Cystine