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Identification of Amides as Carboxylic Acid Surrogates for Quinolizidinone-Based M1 Positive Allosteric Modulators

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Departments of Medicinal Chemistry, Alzheimer's Research, and §Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, P.O. Box 4, West Point, Pennsylvania 19486, United States
*Tel: 215-652-5147. Fax: 215-652-3971. E-mail: [email protected]
Cite this: ACS Med. Chem. Lett. 2012, 3, 12, 1070–1074
Publication Date (Web):October 13, 2012
Copyright © 2012 American Chemical Society

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    Abstract Image

    Selective activation of the M1 muscarinic receptor via positive allosteric modulation represents an approach to treat the cognitive decline in patients with Alzheimer's disease. A series of amides were examined as a replacement for the carboxylic acid moiety in a class of quinolizidinone carboxylic acid M1 muscarinic receptor positive allosteric modulators, and leading pyran 4o and cyclohexane 5c were found to possess good potency and in vivo efficacy.

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    Cited By

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