On the stability of 2-aminoselenophene-3-carboxylates: potential dual-acting selenium-containing allosteric enhancers of A1 adenosine receptor binding

Org Biomol Chem. 2007 Apr 21;5(8):1276-81. doi: 10.1039/b700812k. Epub 2007 Mar 15.

Abstract

Ethyl-2-amino-4,5,6,7-tetrahydro-1-benzoselenophene-3-carboxylate (4), has been prepared as a potential dual-acting selenium-containing allosteric enhancer of adenosine A(1)A receptor binding utilising a modified Gewald reaction. While preliminary testing indicated that 4 is a superior enhancer of A(1)AR binding than its thiophene counterpart, its instability under mildly acidic conditions is cause for concern. X-Ray crystallography, together with DFT calculations, provide evidence that the decomposition of 4 involves the ring-opening of selenophenium ion (12b) followed by the loss of elemental selenium through a radical chain process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Binding Sites
  • Computer Simulation
  • Crystallography, X-Ray
  • Models, Chemical
  • Models, Molecular
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry*
  • Organoselenium Compounds / pharmacology*
  • Receptor, Adenosine A1 / chemistry
  • Receptor, Adenosine A1 / drug effects*
  • Structure-Activity Relationship

Substances

  • Organoselenium Compounds
  • Receptor, Adenosine A1