2-Aryladenine derivatives as a potent scaffold for A1, A3 and dual A1/A3 adenosine receptor antagonists: Synthesis and structure-activity relationships

Abstract

From a collection containing more than 1500 academic compounds, in silico screening identified a hit for the human A₁ adenosine receptor containing a new purine scaffold. To study the structure activity relationships of this new chemical series for adenosine receptors, a library of 24 purines was synthesized and tested in radioligand binding assays at human A₁, A_2A, A_2B and A₃ adenosine receptor subtypes. Fourteen molecules showed potent antagonism at A₁, A₃ or dual A₁/A₃ adenosine receptors. This purine scaffold is an important source for novel biochemical tools and/or therapeutic drugs.

Keywords: 2-Arylpurine derivatives; Adenine derivatives; Adenosine receptor antagonists.