Date of Award


Document Type


Degree Name

Master of Science (MS)


College of Science and Mathematics


Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

David Rotella

Committee Member

David Konas

Committee Member

Magnus Bebbington


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.

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