New aromatic monoesters of alpha-aminoaralkylphosphonic acids as inhibitors of aminopeptidase N/CD13

Bioorg Med Chem. 2010 Apr 15;18(8):2930-6. doi: 10.1016/j.bmc.2010.02.056. Epub 2010 Mar 1.

Abstract

A series of new aromatic monoesters of alpha-aminoaralkylphosphonic acids were synthesized by selective hydrolysis of corresponding aromatic diesters of alpha-aminoaralkylphosphonic acids. New potential inhibitors of aminopeptidase N/CD13, an enzyme important in tumour angiogenesis, were developed. Some derivatives of the homophenylalanine and norleucine related monoaryl phosphonates displayed higher inhibition potency than corresponding alpha-aminoaralkylphosphonic acids toward aminopeptidase N/CD13. The effect of one of the new inhibitors on the growth of human PANC-1 and HT-1080 cell lines was examined, either alone or in combination with TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / metabolism
  • Cell Line, Tumor
  • Humans
  • Phosphinic Acids / chemical synthesis
  • Phosphinic Acids / chemistry*
  • Phosphinic Acids / pharmacology
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Angiogenesis Inhibitors
  • Phosphinic Acids
  • Protease Inhibitors
  • Tumor Necrosis Factor-alpha
  • CD13 Antigens