A_2B adenosine receptor antagonists and their potential indications

Abstract

The intense efforts by many pharmaceutical companies and academics in the A_2B adenosine receptor (AdoR) antagonist field are driven by the plethora of disease states where the A_2B 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 A_2B adenosine receptor (AdoR) antagonists containing different classes of core heterocycles, including xanthines, 7-deazadenines and pyrimidines. The high affinity A_2B 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 A_2B AdoR antagonist has been met by several research groups and this will help address the role of the A_2B AdoR in asthma, diabetes, cancer and management of inflammatory pain.