Current data continues to indicate an important relationship between neuroinflammation and neuropsychiatric disorders. We have explored inhibitors of the P2X7 receptor, a target that resides along a pro-inflammatory cascade and is expressed systemically as well as in the brain. This presentation will focus on the synthesis and characterization of novel 5,6-fused P2X7 antagonists. Highlights include the development of a single pot dipolar cycloaddition reaction / Cope elimination sequence to access 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridines that contain a synthetically challenging chiral center. The successful implementation of the chemistry has allowed for prompt advancement of candidates to the clinic.








Christa Chrovian (Janssen Research and Development)