Identification of new mechanisms to treat the neurodegenerative effects of Alzheimer's disesase (AD) represents a major unmet medical need. One approach to ameliorate the cognitive decline in AD has been to target the neurons of the basal forebrain cholinergic system via activiation of the M1 muscarinic receptor. Non-selective M1 muscarinic agonists have previously shown positive cognitive effects in AD patients, but were limited due to cholinergic events due to lack of selectivity. One strategy to confer selectivity is to target an alloseric site on the receptor, rather than the highly conserved orthosteric site. This presentation describes the chemical evolution of HTS lead quinolone carboxylic acid BQCA into a highly selective quinolizidinone class of M1 PAMs with pharmacokinetic and in vivo properties.

Chemical evolution of quinolizidinone M<sub>1</sub> positive allosteric modulators

243rd National Meeting (2012)

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Chemical evolution of quinolizidinone M1 positive allosteric modulators

Chemical evolution of quinolizidinone M₁ positive allosteric modulators