Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors

Org Biomol Chem. 2009 Jan 7;7(1):27-9. doi: 10.1039/b819155g. Epub 2008 Nov 17.

Abstract

A modular replacement approach to the synthesis of sulfo-nucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection.

Publication types

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

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Chemistry, Pharmaceutical / methods
  • Cytoplasm / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Humans
  • Kinetics
  • Models, Chemical
  • N-Acylneuraminate Cytidylyltransferase / antagonists & inhibitors*
  • N-Acylneuraminate Cytidylyltransferase / chemistry*
  • Neisseria meningitidis / enzymology
  • Nucleotides / chemistry
  • Polysaccharides / chemistry
  • Sulfones / chemistry*

Substances

  • Enzyme Inhibitors
  • Nucleotides
  • Polysaccharides
  • Sulfones
  • N-Acylneuraminate Cytidylyltransferase