Synthesis of Allosteric Modulators for Nicotinic Acetylcholine Receptors

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Title: Synthesis of Allosteric Modulators for Nicotinic Acetylcholine Receptors
Creators: Young, Jason
Advisor: Werbovetz, Karl; Coleman, Robert
Issue Date: 2012-06
Abstract: Nicotinic acetylcholine receptors (nAChR) can be found throughout the human nervous system. The receptors regulate a multitude of functions, including development, inflammation, and movement. They also serve as the receptor site for nicotine, an extremely addictive drug. Novel therapeutic strategies for breaking this addiction involve synthesis of negative allosteric modulators that could deactivate the binding site for nicotine on these receptors. However, because many subtypes of the nAChR exist, it is difficult to target one without affecting others. This study aims to synthesize a series of analogs of compound 16, an arylsulfonyl piperazine-containing compound that was previously shown to display selectivity for the Hα4β2 nAChR compared to the Hα3β4 nAChR receptor subtype. Synthetic pathways are focused on amide bond formation between substituted arylsulfonyl piperazines and aryl amines. Nine derivatives of 16 have been synthesized. Results confirm the identity of these compounds by 1H, 13C, m/z, and elemental analyses. Biological testing of these compounds has, thus far, shown that the analogs retain the potency of 16 for the Hα4β2 nAChR, but have lost selectivity for that receptor subtype. Future work will focus on exploring different hypotheses regarding the basis of 16 receptor subtype selectivity through the synthesis and evaluation of additional analogs.
Embargo: No embargo
Series/Report no.: The Ohio State University. Personalized Study Program Honors Theses; 2012
Keywords: chemistry
Sponsors: College of Arts and Sciences
NIH Grant R21 DA029433
Description: College of Arts and Sciences Undergraduate Research Scholarship
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