Synthesis and Pharmacological Evaluation of M₄ Muscarinic Receptor Positive Allosteric Modulators Derived from VU10004

The M₄ mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M₄ PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno­[2,3-<i>b</i>]­pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (<i>K</i>_B), cooperativity (αβ), and direct agonist properties (τ_B)