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Antagonism of the adenosine A 2A  receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an  in vivo  immunoassay based on the Concanavalin A mouse model, a series of A 2A  antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant, including fluorinated polyethylene glycol PEGylated derivatives. The efficacy of the analogs was evaluated using two  in vitro  functional bioassays, and compound  29 , a fluorinated triethylene glycol derivative of preladenant, was confirmed as a potential immunotherapeutic agent.

Fluorinated Adenosine A2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics

Fluorinated Adenosine A_2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics