Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3152-5. doi: 10.1016/j.bmcl.2007.03.035. Epub 2007 Mar 15.

Abstract

A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • Molecular Structure
  • NAD / chemistry
  • Sulfonamides / chemistry

Substances

  • Enzyme Inhibitors
  • Sulfonamides
  • methylenebis(sulfonamide)
  • NAD
  • IMP Dehydrogenase