MK-7622: A First-in-Class M 1 Positive Allosteric Modulator Development Candidate.

Douglas C Beshore,Christina N Di Marco,Ronald K Chang,Thomas J Greshock,Lei Ma,Marion Wittmann,Matthew A Seager,Kenneth A Koeplinger,Charles D Thompson, Joy Fuerst,George D Hartman,Mark T Bilodeau,William J Ray,Scott D Kuduk

ACS medicinal chemistry letters（2018）

Cited 24|Views54

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Abstract

Identification of ligands that selectively activate the M 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 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.

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