• Adenosine receptor antagonists
• A2B adenosine receptor subtypes

Adenosine is an endogenous purine nucleoside that play a key role in numerous important physiological functions through interaction with specific cell-surface-G-protein-coupled receptors, which are classified into four subtypes, namely A1, A2A, A2B and A3 Adenosine Receptors (ARs).
A2B ARs have been generally defined as the “low affinity ARs”, due to their low affinity for the endogenous ligand and for other typical agonist (i.e.: NECA, R-PIA). During emergency situations adenosine is normally increased and can grow to very high micromolar concentrations and thus activates the A2B as well.
A2B AR activation implies stimulation of adenylate cyclase and activation of phospholipase C through coupling to Gs and Gq/11 proteins, producing an increase in intracellular cAMP and calcium ion levels.
This receptor plays a crucial role in the regulation of wide range of physiopathological events, such as the genesis of inflammatory processes, angiogenesis induction, glucose metabolism and the grow and the development of some tumours. In view of these findings, high affinity and selective A2B AR antagonist are neened as valuable tools to fully establish their therapeutic potential for treatment of inflammatory disease such as asthma and colitis, angiogenic disease like diabetic retinopathy and cancer.
In an effort to identify novel ligands possessing high affinity and selectivity for A2B AR subtype, the research group I worked with investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones, previously discovered as selective A1 AR antagonists. Preliminary assays were performed on a number of compounds selected from the “in-house” collection. Binding data revealed that all the derivates showed significant affinity to A2B AR. These data represented the rationale for the study of a new series of triazinobenzimidazole featuring modified substituents at the 10-position (4'-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position of the triazinobenzimidazole nucleus.