Synthesis and biological evaluation of 2-aminothiazoles and their amide derivatives on human adenosine receptors. Lack of effect of 2-aminothiazoles as allosteric enhancers

Bioorg Med Chem. 2005 Mar 15;13(6):2079-87. doi: 10.1016/j.bmc.2005.01.006.

Abstract

A number of 2-aminothiazoles (2a-e) and their amide derivatives (4-10) were prepared. The 2-aminothiazoles themselves were tested as allosteric enhancers of agonist binding to human adenosine A(1) receptors. In a variety of experimental set-ups the compounds did not show any such effect, in contrast to earlier findings by another research group. Subsequently the 2-aminothiazoles were used as intermediates in the synthesis of a number of amide derivatives of either aromatic (4-6) or aliphatic nature (7-10). Some of the compounds emerged as moderately active antagonists on human adenosine A(1) and/or A(2A) receptors with lower or negligible potency at adenosine A(3) receptors.

MeSH terms

  • Allosteric Regulation / drug effects
  • Amides / chemistry*
  • Animals
  • CHO Cells
  • Colforsin / pharmacology
  • Cricetinae
  • Cyclic AMP / biosynthesis
  • Humans
  • Molecular Structure
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / metabolism*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology*

Substances

  • Amides
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Thiazoles
  • Colforsin
  • 2-aminothiazole
  • Cyclic AMP