A2AAR antagonist 5 is a selective A2AAR antagonist that inhibits NECA-stimulated adenylyl cyclase activity in hA2AAR-expressing CHO cells, with an IC50 of 1863 nM. It also shows strong free radical scavenging activity, with an EC50 of 22.21 μM in the DPPH assay. Notably, A2AAR antagonist 5 exhibits significant neuroprotective effects in in vitro models of cerebral ischemia and is applicable for research in cerebral ischemia studies.

A2A receptor (human):1863 nM

A2AAR antagonist 5 (Compound 3) exhibits high affinity for the hA2A adenosine receptor with a K\(_i\) value of 57 nM, shows no affinity for the hA1 adenosine receptor (K\(_i\) > 30,000 nM), and demonstrates moderate affinity for the hA3 adenosine receptor (K\(_i\) = 358 nM). It displays no activity toward the hA2B adenosine receptor (IC\(_{50}\) > 30,000 nM). In CHO cells expressing the hA2A adenosine receptor, A2AAR antagonist 5 acts as an antagonist with an IC\(_{50}\) of 1416 nM in inhibiting NECA-stimulated adenylate cyclase activity. Additionally, A2AAR antagonist 5 shows strong free radical scavenging activity, with an EC\(_{50}\) of 22.21 μM. Administering A2AAR antagonist 5 at a concentration of 200 nM, 15 minutes before, during, and 5 minutes after oxygen-glucose deprivation (OGD), significantly delays OGD-induced anoxic depolarization (AD) in acute rat hippocampal slices in the CA1 region. Furthermore, doses of 1-10 μM during a 30-minute OGD period and subsequent 24-hour recovery also provide significant neuroprotective effects, reducing neuronal damage in the CA1 area of organotypic rat hippocampal slices.