3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2

Bioorg Med Chem Lett. 2004 Feb 23;14(4):865-8. doi: 10.1016/j.bmcl.2003.12.031.

Abstract

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology*
  • Aminopeptidases / antagonists & inhibitors*
  • Binding Sites / drug effects
  • Cell Division / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Metalloendopeptidases / antagonists & inhibitors*
  • Methionine / drug effects
  • Models, Biological
  • Models, Molecular
  • Molecular Structure

Substances

  • Amides
  • Enzyme Inhibitors
  • Methionine
  • Aminopeptidases
  • methionine aminopeptidase 2
  • Metalloendopeptidases