Synthesis and evaluation of aminophosphinic acid derivatives as inhibitors of renal dipeptidase

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3531-3. doi: 10.1016/j.bmcl.2004.04.057.

Abstract

Renal dipeptidase (RDP) is an enzyme overexpressed in benign and malignant colorectal tumors. In an effort to identify potent inhibitors of this enzyme, a series of aminophosphinic acid derivatives were synthesized. Compounds 3a and 3c in which the phenyl ring was para substituted with F and Br and olefin with Z geometry, showed better inhibitory activity against RDP enzyme (IC50 = 5-6 nM).

Publication types

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

MeSH terms

  • Alkenes / chemistry
  • Alkenes / pharmacology
  • Bromides / chemistry
  • Bromides / pharmacology
  • Colorectal Neoplasms / pathology
  • Dipeptidases / antagonists & inhibitors*
  • Dipeptidases / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Fluorides / chemistry
  • Fluorides / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Kidney / enzymology
  • Models, Chemical
  • Phosphinic Acids / chemical synthesis*
  • Phosphinic Acids / pharmacology

Substances

  • Alkenes
  • Bromides
  • Enzyme Inhibitors
  • Phosphinic Acids
  • Dipeptidases
  • dipeptidase
  • Fluorides