The design and synthesis of inhibitors of adenosine 5'-monophosphate deaminase

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1985-90. doi: 10.1016/s0960-894x(99)00298-x.

Abstract

Carbocylic coformycin (4) is a potent herbicide whose primary mode of action involves inhibition of adenosine 5'-monophosphate deaminase (AMPDA) following phosphorylation of the 5'-hydroxyl group in vivo. The search for more stable and accessible structures led to the synthesis of carbocyclic nebularine (8) and deaminoformycin (10). The latter compound is a good herbicide and its corresponding 5'-monophosphate 14 is a strong inhibitor of plant AMPDA (IC50 100 nM).

MeSH terms

  • AMP Deaminase / antagonists & inhibitors*
  • Adenosine / analogs & derivatives
  • Adenosine / chemistry
  • Adenosine Triphosphate / metabolism
  • Coformycin / analogs & derivatives
  • Coformycin / chemistry
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Formycins / chemistry*
  • Formycins / pharmacology*
  • Herbicides / chemistry*
  • Herbicides / pharmacology
  • Inhibitory Concentration 50
  • Phosphorylation
  • Purine Nucleosides / chemistry
  • Purine Nucleosides / metabolism
  • Ribonucleosides / chemistry
  • Ribonucleosides / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Formycins
  • Herbicides
  • Purine Nucleosides
  • Ribonucleosides
  • deamineformycin
  • Coformycin
  • aristeromycin
  • Adenosine Triphosphate
  • nebularine
  • AMP Deaminase
  • Adenosine