Synthesis and immunobiological activity of base substituted 2-amino-3-(purin-9-yl)propanoic acid derivatives

Bioorg Med Chem. 2005 Apr 1;13(7):2349-54. doi: 10.1016/j.bmc.2005.01.054.

Abstract

2-Amino-3-(purin-9-yl)propanoic acids substituted at position 6 of the purine base moiety by dimethylamino, cyclopropylamino, pyrrolidin-1-yl, hydroxy, and sulfanyl group as well as their 2-aminopurine analogues were prepared from corresponding 9-(2,2-diethoxyethyl)purines and 2-aminopurines, respectively, by the Strecker synthesis. 2-Aminopropanoic acid derivatives were tested for their immunostimulatory and immunomodulatory potency. Some of these compounds significantly enhanced secretion of chemokines RANTES and MIP-1alpha, the most potent was 2-amino-6-sulfanylpurine derivative. Most of these compounds also augmented NO biosynthesis triggered primarily by IFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / immunology
  • Chemokine CCL5 / metabolism
  • Female
  • Immunologic Tests
  • Interferon-gamma / pharmacology
  • Macrophage Inflammatory Proteins / immunology
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Nitric Oxide / biosynthesis
  • Propionates / chemical synthesis*
  • Propionates / immunology
  • Propionates / pharmacology*
  • Structure-Activity Relationship

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Macrophage Inflammatory Proteins
  • Propionates
  • Nitric Oxide
  • Interferon-gamma