Synthesis of theophylline derivatives and study of their activity as antagonists at adenosine receptors

The synthesis of oligo(ethylene glycol)-alkene substituted theophyllines in positions 7 and/or 8 is described. The binding activity at adenosine receptors of selected derivatives was studied. Compound 2 showed high affinity for human A2B receptor (Ki = 4.16 nM) with a selectivity KiA2A/KiA2B of 24.1, and a solubility in water of 1 mM. The alkenyl substituent in some of the theophylline derivatives allows for covalent attachment of them onto hydrogen-terminated silicon substrate surfaces via hydrosilylation. Alternatively, an azido group was incorporated to an oligo(ethylene glycol)theophylline derivative as an anchor for tethering the molecules on ethynyl presenting surfaces via click reaction.

Synthesis of oligo(ethylene glycol)-alkene substituted the theophyllines (positions 7 and/or 8) is described. Compound 2 showed high affinity and selectivity for A2B receptor (Ki = 4.16 nM, KiA2A/KiA2B = 24.1). The alkenyl or azido substituents in some of the derivative allows for covalent attachment of them onto H-terminated silicon surfaces.Figure optionsDownload as PowerPoint slide