{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/35829"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/35829","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Potential Prodrugs of the Neuronal Nitric Oxide Synthase and Monoamine Oxidase Inhibitor 7-Nitroindazole and Structurally Related Compounds","abstract":"Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown cause that afflicts about 1.5 million Americans. The characteristic feature of PD is a deficiency of dopamine in the terminals of nigrostriatal neurons. Two enzyme systems, the neuronal form of nitric oxide synthase (nNOS) and monoamine oxidase B (MAO-B), have been linked to neurodegenerative pathways leading to PD. Several MAO-B and nNOS inhibitors have been evaluated for their neuroprotective properties in the mouse model of neurodegeneration which employs the parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One such compound is 7-nitroindazole (7-NI), a compound which is reported to inhibit both enzymes. This thesis focuses on the synthesis and biological evaluation of a potential prodrug form of 7-NI and related indazolyl containing compounds which are designed to release the active drugs following a metabolic bioactivation process. These studies have led to a detailed description of the nucleophilic aromatic substitution reactions between 4-chloro-1-methylpyridinium iodide and the indazolyl reactants that were employed as the initial step in the synthesis of the target compounds. The MAO-B substrate and inhibition properties of these \"prodrugs\" as well as the parent indazolyl compounds were examined. The results are discussed in relation to a previously developed active site model of MAO-B.","abstract_html":"Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown cause that afflicts about 1.5 million Americans. The characteristic feature of PD is a deficiency of dopamine in the terminals of nigrostriatal neurons. Two enzyme systems, the neuronal form of nitric oxide synthase (nNOS) and monoamine oxidase B (MAO-B), have been linked to neurodegenerative pathways leading to PD. Several MAO-B and nNOS inhibitors have been evaluated for their neuroprotective properties in the mouse model of neurodegeneration which employs the parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One such compound is 7-nitroindazole (7-NI), a compound which is reported to inhibit both enzymes. This thesis focuses on the synthesis and biological evaluation of a potential prodrug form of 7-NI and related indazolyl containing compounds which are designed to release the active drugs following a metabolic bioactivation process. These studies have led to a detailed description of the nucleophilic aromatic substitution reactions between 4-chloro-1-methylpyridinium iodide and the indazolyl reactants that were employed as the initial step in the synthesis of the target compounds. The MAO-B substrate and inhibition properties of these "prodrugs" as well as the parent indazolyl compounds were examined. The results are discussed in relation to a previously developed active site model of MAO-B.","abstract_has_math":false,"creators":["Isin, Emre M."],"institution":"Virginia Tech","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Chemistry","degree_department":"Chemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Castagnoli, Neal Jr."],"committee_members":["Kingston, David G. I.","Tanko, James M.","Dorn, Harry C."],"year":2000,"date_issued":"2000-10-30","date_published":"2000-10-30","updated_at":"2026-07-22T22:20:21Z","subjects":["indazole","neuroprotection","organic reaction mechanisms","SAR","tetrahydropyridinyl-based prodrugs"],"languages":[],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-11272000-120319"],"render_values":[{"text":"etd-11272000-120319","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/35829","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Castagnoli, Neal Jr."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Kingston, David G. I.","Tanko, James M.","Dorn, Harry C."]},{"key":"dc:contributor.department","label":"Department","values":["Chemistry"]},{"key":"dc:creator","label":"Author","values":["Isin, Emre M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-03-14T20:48:23Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-14T20:48:23Z","2001-12-06"]},{"key":"dc:date.issued","label":"Date","values":["2000-10-30"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["indazole","neuroprotection","organic reaction mechanisms","SAR","tetrahydropyridinyl-based prodrugs"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-11272000-120319"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10919/35829"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown cause that afflicts about 1.5 million Americans. The characteristic feature of PD is a deficiency of dopamine in the terminals of nigrostriatal neurons. Two enzyme systems, the neuronal form of nitric oxide synthase (nNOS) and monoamine oxidase B (MAO-B), have been linked to neurodegenerative pathways leading to PD. Several MAO-B and nNOS inhibitors have been evaluated for their neuroprotective properties in the mouse model of neurodegeneration which employs the parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One such compound is 7-nitroindazole (7-NI), a compound which is reported to inhibit both enzymes. This thesis focuses on the synthesis and biological evaluation of a potential prodrug form of 7-NI and related indazolyl containing compounds which are designed to release the active drugs following a metabolic bioactivation process. These studies have led to a detailed description of the nucleophilic aromatic substitution reactions between 4-chloro-1-methylpyridinium iodide and the indazolyl reactants that were employed as the initial step in the synthesis of the target compounds. The MAO-B substrate and inhibition properties of these \"prodrugs\" as well as the parent indazolyl compounds were examined. The results are discussed in relation to a previously developed active site model of MAO-B."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science"]},{"key":"dc:title","label":"Title","values":["Potential Prodrugs of the Neuronal Nitric Oxide Synthase and Monoamine Oxidase Inhibitor 7-Nitroindazole and Structurally Related Compounds"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Castagnoli, Neal Jr."],"dc:contributor.committeemember":["Kingston, David G. I.","Tanko, James M.","Dorn, Harry C."],"dc:contributor.department":["Chemistry"],"dc:creator":["Isin, Emre M."],"dc:date.accessioned":["2014-03-14T20:48:23Z"],"dc:date.available":["2014-03-14T20:48:23Z","2001-12-06"],"dc:date.issued":["2000-10-30"],"dc:description.abstract":["Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown cause that afflicts about 1.5 million Americans. The characteristic feature of PD is a deficiency of dopamine in the terminals of nigrostriatal neurons. Two enzyme systems, the neuronal form of nitric oxide synthase (nNOS) and monoamine oxidase B (MAO-B), have been linked to neurodegenerative pathways leading to PD. Several MAO-B and nNOS inhibitors have been evaluated for their neuroprotective properties in the mouse model of neurodegeneration which employs the parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One such compound is 7-nitroindazole (7-NI), a compound which is reported to inhibit both enzymes. This thesis focuses on the synthesis and biological evaluation of a potential prodrug form of 7-NI and related indazolyl containing compounds which are designed to release the active drugs following a metabolic bioactivation process. These studies have led to a detailed description of the nucleophilic aromatic substitution reactions between 4-chloro-1-methylpyridinium iodide and the indazolyl reactants that were employed as the initial step in the synthesis of the target compounds. The MAO-B substrate and inhibition properties of these \"prodrugs\" as well as the parent indazolyl compounds were examined. The results are discussed in relation to a previously developed active site model of MAO-B."],"dc:description.degree":["Master of Science"],"dc:identifier.other":["etd-11272000-120319"],"dc:identifier.uri":["http://hdl.handle.net/10919/35829"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["indazole","neuroprotection","organic reaction mechanisms","SAR","tetrahydropyridinyl-based prodrugs"],"dc:title":["Potential Prodrugs of the Neuronal Nitric Oxide Synthase and Monoamine Oxidase Inhibitor 7-Nitroindazole and Structurally Related Compounds"],"dc:type":["Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:21Z"}