Virginia Tech
Studies on the Synthesis and Rearrangement of Indazolylpyridinium Derivatives Precursors to Potential Neuroprotective Prodrugs Bearing a 1,2,3,6-Tetrahydropyridinyl Carrier
Abstract
dc:description.abstractThe neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) protects against the neurotoxicity of MPTP in a mouse model of neurodegeneration. Since 7-NI also inhibits the monoamine oxidase-B (MAO-B) catalyzed bioactivation of MPTP, the role of nNOS inhibition as a mediator of 7-NI's neuroprotective properties have been challenged. In order to examine in greater detail the neuroprotective effects of indazolyl derivatives, the synthesis of water soluble indazolyltetrahydropyridinyl derivatives as potential "prodrugs" that may undergo MAO bioactivation in the brain was undertaken. During the course of the studies on the synthesis of indazolylpyridinium derivatives, precursors to these "prodrugs", an interesting reaction involving the rearrangement of 4-(2H-indazolyl)-1-methylpyridinium iodide to the corresponding 1H-isomer was encountered. A detailed investigation of this rearrangement reaction is reported in this thesis. The syntheses and interaction of nitroindazolyltetrahydropyridinyl "prodrugs" with MAO-B have been investigated previously. Molecular docking studies that attempt to explain the MAO-B substrate and inhibitor properties of members of this series of compounds are described. Finally, the MAO-A substrate properties of nitroindazolyltetrahydropyridinyl derivatives are reported.
Degree
thesis:*- Name thesis:degree_name
- Ph. D.
- Level thesis:degree_level
- doctoral
- Discipline thesis:degree_discipline
- Chemistry
- Department dc:contributor.department
- Chemistry
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 2004
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Isin, Emre Mehmet
- Chair dc:contributor.committeechair
-
- Castagnoli, Neal Jr.
- Committee members dc:contributor.committeemember
-
- Kingston, David G. I.
- Bevan, David R.
- Carlier, Paul R.
- Tanko, James M.
Subjects
dc:subject × 6Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
Identifiers
dc:identifier.*- Dc Identifier Other
- etd-04272004-162852
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/27363