Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

Bioorg Med Chem. 2013 Mar 1;21(5):1209-18. doi: 10.1016/j.bmc.2012.12.032. Epub 2013 Jan 4.

Abstract

A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC(50) value of 1.6 μM in the MLR assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / toxicity
  • Jurkat Cells
  • Lymphocyte Culture Test, Mixed
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / toxicity
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Immunosuppressive Agents
  • Pyrimidines
  • pyrimidine