Design, synthesis and biological evaluation of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine: Towards adenosine A2A receptor (A2A AR) antagonist.

Antagonists of adenosine receptor are under exploration as potential drug candidates for treatment of neurological disorders, depression, certain cancers and potentially used as a cancer immunotherapy. Herein, we describe design and synthesis of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine (6) derivatives. All the compounds were evaluated for A2A AR antagonist activity and displayed encouraging results (IC50 9-300 nM) of A2A AR antagonist binding affinity in biochemical assay. Compound 27 exhibits good activity in A2A AR antagonist cAMP functional assay (IC50 31 nM) and further this compound shows T-cell activation at the IL-2 production assay (EC50 165 nM). Molecular docking studies were carried out to rationalize the observed binding affinity of compound 27.