Identification of amides as carboxylic Acid surrogates for quinolizidinone-based m1 positive allosteric modulators

ACS Med Chem Lett. 2012 Oct 13;3(12):1070-4. doi: 10.1021/ml300280g. eCollection 2012 Dec 13.


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: carboxylic acid surrogates; positive allosteric modulators; quinolizidinone.