Title page for ETD etd-11062006-094848

Type of Document Master's Thesis
Author Downey, Aaron
URN etd-11062006-094848
Title Synthesis and MAO activity of a series of benzimidazolyl and indazolyl prodrugs
Degree Master of Science
Department Chemistry
Advisory Committee
Advisor Name Title
Castagnoli, Neal Jr. Committee Chair
Gandour, Richard D. Committee Member
Tanko, James M. Committee Member
  • Neurodegeneration
  • oxidative stress
  • enzyme kinetics
Date of Defense 2006-10-27
Availability unrestricted
Parkinson's disease (PD) is a chronic, progressive disorder of the central nervous system that affects approximately 1.5 million Americans. One of the principal pathological features of PD is dopamine deficiency in the substantia nigra of the brain. A key enzyme that has been associated with the neurodegeneration seen in PD is monoamine oxidase-B (MAO-B). Several inhibitors of this enzyme have resulted in neuroprotection in the mouse model of PD. One such compound is 7-nitroindazole (1).

This thesis describes the synthesis and MAO activity of several indazolyl and benzimidazolyl prodrugs that are designed to release an enzyme inhibitor in the affected brain area. These studies have provided information regarding the nucleophilic aromatic substitutions of the ambident nucleophiles under consideration. We have also discovered a compound that releases the enzyme inhibitor upon bioactivation by MAO. These results as well as a MPTP mouse study with the aforementioned compound are detailed within.

  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  AaronDowneythesis2.pdf 648.42 Kb 00:03:00 00:01:32 00:01:21 00:00:40 00:00:03

Browse All Available ETDs by ( Author | Department )

dla home
etds imagebase journals news ereserve special collections
virgnia tech home contact dla university libraries

If you have questions or technical problems, please Contact DLA.