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

Abstract

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 <b>4o</b> and cyclohexane <b>5c</b> were found to possess good potency and in vivo efficacy