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 A 2A AR antagonist activity and displayed encouraging results (IC 50 9–300 nM) of A 2A AR antagonist binding affinity in biochemical assay. Compound 27 exhibits good activity in A 2A AR antagonist cAMP functional assay (IC 50 31 nM) and further this compound shows T-cell activation at the IL-2 production assay (EC 50 165 nM). Molecular docking studies were carried out to rationalize the observed binding affinity of compound 27. Image 1 • Design new benzo[4,5]imidazo[1,2- a ]pyrazin-1-amine scaffold • Developed simple protocol for the synthesis of benzo[4,5]imidazo[1,2- a ]pyrazin-1-amine scaffold analogues • This new analogues biological evaluated for Adenosine A 2A receptor (A 2A) antagonist activity • cAMP Functional assays of the hA 2A AR in human HEK-293 cells, compound 27 showed nonomolar potency with IC 50 = 31 nM • Compound 27 stimulate IL-2 production by T cell activation with nonomolar potency i.e. EC 50 = 165 nM [ABSTRACT FROM AUTHOR]