Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers

Bioorg Med Chem. 2008 Oct 15;16(20):9212-6. doi: 10.1016/j.bmc.2008.09.017. Epub 2008 Sep 9.

Abstract

DZ2002 and its related stereoisomers were efficiently synthesized. The optical data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In accordance with respective inhibitory potency of SAHase, the immunosuppressive potency order was demonstrated as (S)-DZ2002>(Rac)-DZ2002>(R)-DZ2002>(Keto)-DZ2002. These results indicate (S)-configuration of 2-chiral center in DZ2002 is important for binding with SAHase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Adenine / chemistry
  • Adenine / pharmacology
  • Adenosylhomocysteinase / antagonists & inhibitors
  • Adenosylhomocysteinase / metabolism
  • Animals
  • Butyrates / chemical synthesis*
  • Butyrates / chemistry
  • Butyrates / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Rabbits
  • Stereoisomerism

Substances

  • Butyrates
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • methyl 4-(adenin-9-yl)-2-hydroxybutanoate
  • Adenosylhomocysteinase
  • Adenine