Date of Award

8-2020

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

David Rotella

Committee Member

David Konas

Committee Member

Magnus Bebbington

Abstract

The orexin system in humans contains receptors Orexin 1 (OX1) and Orexin 2 (OX2). These receptors are involved in numerous physiological processes including wake/sleep cycling, energy homeostasis, and motivation/reward. In scientific literature, it is known that antagonism of these receptors exhibits therapeutic effects in the realm of cocaine and alcohol addiction, as well as sleep disorders. On the market today exist drugs for treatment of sleep disorders through orexin receptor antagonization. Here we report a synthesis toward novel conformationally rigid antagonists of the orexin receptor system that may provide improved affinity and/or selectivity compared to known compounds. We report the synthesis of a conformationally-restricted bicyclic diamine scaffold with intrinsic structural properties that could assist in improving the binding affinity of known orexin receptor antagonists by enabling the optimization functionalization of chemically distinguishable endocyclic nitrogen atoms.

File Format

PDF

Included in

Chemistry Commons

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