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

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• 作者：Scott D. Kuduk ; Ronald K. Chang ; Thomas J. Greshock ; William J. Ray ; Lei Ma ; Marion Wittmann ; Matthew A. Seager ; Kenneth A. Koeplinger ; Charles D. Thompson ; George D. Hartman ; Mark T. Bilodeau
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：3
• 期：12
• 页码：1070-1074
• 全文大小：369K
• 年卷期：v.3,no.12(December 13, 2012)
• ISSN：1948-5875

文摘

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.

Keywords:

d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=carboxylic+acid+surrogates&qsSearchArea=searchText">carboxylic acid surrogates; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=quinolizidinone&qsSearchArea=searchText">quinolizidinone; d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=positive+allosteric+modulators&qsSearchArea=searchText">positive allosteric modulators