The observed shift towards activated P2Y12-negative microglia in neurodegenerative diseases such as AD in their early stages has significant implications for diagnosis, monitoring and therapeutic intervention assessment. However, the availability of a highly selective and specific PET tracer with optimal physicochemical properties for brain uptake and clearance is a prerequisite, given the gradual decrease of target throughout disease progression. Although previous attempts with compounds 1-5 have yielded promising in vitro results as potent P2Y12R inhibitors, they only exhibited limited brain uptake, thus rendering PET imaging P2Y12R in the context of neuroinflammation in the CNS impossible. The objective of this study was to identify a AZD1283 derived compound in order to facilitate the BBB passage while maintaining a sufficient degree of affinity for the target receptor.