P-21 Design and Synthesis of a Novel Isoxazoline as a Potential PAM-Agonist

Abstract

Progression of Alzheimer’s disease is associated with a loss of M1 receptor activation in the brain. However, a lack of clinical success following attempts to activate the M1 receptor at the orthosteric site has contributed to a transition towards the allosteric pocket of the receptor. Here, positive allosteric modulators (PAMs) interact to potentiate the acetylcholine response. Recent research proposes that optimization of PAM activity at the expense of intrinsic agonism may posit a means to limit adverse side effects. Therefore, this project proposes a design and synthesis of a novel isoxazoline as a potent PAM agent with weak intrinsic agonism.

Acknowledgments

Supervising Professor: Dr. Lisa Ahlberg

Location

Buller Hall Lobby

Start Date

3-8-2019 2:30 PM

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Mar 8th, 2:30 PM

P-21 Design and Synthesis of a Novel Isoxazoline as a Potential PAM-Agonist

Buller Hall Lobby

Progression of Alzheimer’s disease is associated with a loss of M1 receptor activation in the brain. However, a lack of clinical success following attempts to activate the M1 receptor at the orthosteric site has contributed to a transition towards the allosteric pocket of the receptor. Here, positive allosteric modulators (PAMs) interact to potentiate the acetylcholine response. Recent research proposes that optimization of PAM activity at the expense of intrinsic agonism may posit a means to limit adverse side effects. Therefore, this project proposes a design and synthesis of a novel isoxazoline as a potent PAM agent with weak intrinsic agonism.