A2B adenosine receptor antagonists and their potential indications

Abstract

The intense efforts by many pharmaceutical companies and academics in the A2B adenosine receptor (AdoR) antagonist field are driven by the plethora of disease states where the A2B AdoR has been implicated to play a role: asthma, in which it mediates inflammatory cytokine release; diabetes, in which it mediates gluconeogenesis; diabetic retinopathy and cancer, in which it mediates angiogenesis; and inflammatory pain, in which it mediates inflammatory cytokine release. Major advances have been made in the past 5 years in obtaining selective, high affinity A2B adenosine receptor (AdoR) antagonists containing different classes of core heterocycles, including xanthines, 7-deazadenines and pyrimidines. The high affinity A2B AdoR antagonists have a high degree of structural diversity that should aid in further drug design attempts and optimisation of drug properties (i.e., solubility, oral bioavailability and half-life) through combinations of structural features from different classes. The goal of obtaining a selective, high affinity A2B AdoR antagonist has been met by several research groups and this will help address the role of the A2B AdoR in asthma, diabetes, cancer and management of inflammatory pain.