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

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 carbox...

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Published in:ACS medicinal chemistry letters 2012-12, Vol.3 (12), p.1070-1074
Main Authors: Kuduk, Scott D, Chang, Ronald K, Greshock, Thomas J, Ray, William J, Ma, Lei, Wittmann, Marion, Seager, Matthew A, Koeplinger, Kenneth A, Thompson, Charles D, Hartman, George D, Bilodeau, Mark T
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Language:English
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300280g