Synthesis and characterization of chiral 6-azaspiro[2.5]octanes as potent and selective antagonists of the M4 muscarinic acetylcholine receptor

Development of a Selective and High Affinity Radioligand, [3H]VU6013720, for the M4Muscarinic Receptor

“…Recently, our group successfully synthesized and characterized several highly selective M 4 receptor antagonists, VU6013720, VU6021302, and VU6021625 (Moehle et al, 2021), VU6028418 (Spock et al, 2021), and VU6015241 (Bender et al, 2022). Of these compounds, VU6013720 exhibited the best in vitro functional potency (rat M 4 IC 50 = 20 nM, human M 4 IC 50 = 0.6 nM from calcium mobilization assays) as well as a good selectivity profile among the muscarinic receptor family, with IC 50 values of >10,000 nM at rM 3 and rM 5 .…”