Design, synthesis and biological evaluation of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine: Towards adenosine A 2A receptor (A 2A 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 A AR antagonist activity and displayed encouraging results (IC 9-300 nM) of A AR antagonist binding affinity in biochemical assay. Compound 27 exhibits good activity in A AR antagonist cAMP functional assay (IC 31 nM) and further this compound shows T-cell activation at the IL-2 production assay (EC 165 nM). Molecular docking studies were carried out to rationalize the observed binding affinity of compound 27.