Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric muscarinic receptor modulators.

Basic Information

ID: ALA2040827

Journal: ACS Med Chem Lett

Title: Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric muscarinic receptor modulators.

Authors: Kuduk SD, Chang RK, Di Marco CN, Ray WJ, Ma L, Wittmann M, Seager MA, Koeplinger KA, Thompson CD, Hartman GD, Bilodeau MT.

Abstract: Positive allosteric modulation of the M1 muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer's disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M1 modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.

CiteXplore: 24900206

DOI: 10.1021/ml100095k

Patent ID: