Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis

Bioorg Med Chem Lett. 1998 Sep 8;8(17):2303-8. doi: 10.1016/s0960-894x(98)00417-x.

Abstract

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Binding Sites
  • Candida albicans / enzymology
  • Cell Wall / metabolism
  • Databases as Topic*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indans / chemical synthesis*
  • Indans / chemistry
  • Indans / pharmacology
  • Indicators and Reagents
  • Kinetics
  • Mannose-6-Phosphate Isomerase / antagonists & inhibitors*
  • Mannose-6-Phosphate Isomerase / chemistry
  • Molecular Structure
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Swine

Substances

  • AF 14049
  • Amides
  • Enzyme Inhibitors
  • Indans
  • Indicators and Reagents
  • Mannose-6-Phosphate Isomerase