Development of Novel Adenosine 2a Receptor Ligands

Perceptive synthesized a series of twenty-four potential A2a ligands, based on the scaffold of preladenant, which could be readily radiohalogenated. This series was screened in vitro for binding efficiency to the A2a receptor. Six of the most potent ligands were radiolabeled with either F-18 or I-123 and screened in vivo in NHP for brain uptake, specific uptake in A2a-rich areas and washout. Of these six, [18F]MNI-444 and [123I]MNI-420 were further validated in NHP before translation into GMP-compliant synthesis and evaluation in humans. Both ligands have been utilized in assessing the changes in A2a receptor density in PD, HD, and AD patients.

Barret et al J. Nuc. Med., 2015, 56(4) 586

Vala et al Chem. Med. Chem., 2016, 11(15), 1936