Abstract
Identification of ligands that selectively activate the M(1) muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M(1) muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.