Traceless solid-phase synthesis and biological evaluation of purine analogs as inhibitors of multidrug resistance protein 4

J Comb Chem. 2007 Mar-Apr;9(2):210-8. doi: 10.1021/cc060084t.

Abstract

The traceless solid-phase syntheses of 6-oxopurines and pyrazolo[3,4-d]pyrimidines are presented. The effects of these compounds on multidrug resistance protein 4 (MRP4/ABCC4) facilitated efflux was examined. Four of the compounds, 7b, 7c, 15a, and 17e, were active in inhibiting MRP4-mediated efflux of the bimane-glutathione conjugate. In addition, all four compounds were also able to reverse MRP4-mediated resistance to the anticancer drug 6-thioguanine. In the presence of 25 microM 15a or 17e, there was complete reversal. The reversal of resistance was achieved without any effects on the uptake and metabolism of 6-thioguanine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Magnetic Resonance Spectroscopy
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
  • Purines / chemical synthesis*
  • Purines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • ABCC4 protein, human
  • Multidrug Resistance-Associated Proteins
  • Purines