{"id":{"repo_id":"bradford","oai_identifier":"oai:bradscholars.brad.ac.uk:10454/4418"},"canonical_url":"https://search.dev.ndltd.org/etd/bradford/oai:bradscholars.brad.ac.uk:10454/4418","repository":{"repo_id":"bradford","name":"University of Bradford","base_url":"https://bradscholars.brad.ac.uk/oai/request"},"display":{"title":"New applications of Imidazotetrazinone prodrugs. Synthesis and mechanistic investigation of novel imidazotetrazinones as prodrugs of aziridines and as traceless carriers for drug delivery to the central nervous system.","abstract":"New imidazotetrazinones have been synthesised that possess features in their structures to release aziridinium ions upon ring opening. Unstable 2-aminoethylisocyanates were required in this preparation, which were synthesized with BOC-protection of the amino group to counteract the reactivity of the amine towards the isocyanate group in the case of aliphatic amines; in contrast, anilinoethylisocyanates were synthesized unprotected. Substituents with a range of electron-withdrawing and electron-releasing properties were introduced at the p-position of the aniline ring. A 13C-labelled study confirmed the release of the aziridinium ion by these imidazotetrazinones in neutral pH buffer solution. Furthermore the kinetics of the hydrolysis in neutral aqueous solution of some these new tetrazines were similar to temozolomide, in addition to useful acid stability. Other imidazotetrazinones were synthesised for the purpose of releasing alcohols and phenols. Their synthesis was performed with a one-carbon linker between the imidazotetrazinone 3-position and the alcohols or phenols to be released. The release of alcohol and phenol through the hydrolysis of the intermediate diazonium ions to the unstable hemiacetals that decomposed to the alcohol and phenol was confirmed by 1H NMR. The kinetics of the hydrolysis of these tetrazines in neutral aqueous solution showed a faster reaction rate compared with temozolomide (t1/2 = 0.53 and 0.36 h compared with temozolomide 1.4 h).","abstract_html":"New imidazotetrazinones have been synthesised that possess features in their structures to release aziridinium ions upon ring opening. Unstable 2-aminoethylisocyanates were required in this preparation, which were synthesized with BOC-protection of the amino group to counteract the reactivity of the amine towards the isocyanate group in the case of aliphatic amines; in contrast, anilinoethylisocyanates were synthesized unprotected. Substituents with a range of electron-withdrawing and electron-releasing properties were introduced at the p-position of the aniline ring. A 13C-labelled study confirmed the release of the aziridinium ion by these imidazotetrazinones in neutral pH buffer solution. Furthermore the kinetics of the hydrolysis in neutral aqueous solution of some these new tetrazines were similar to temozolomide, in addition to useful acid stability. Other imidazotetrazinones were synthesised for the purpose of releasing alcohols and phenols. Their synthesis was performed with a one-carbon linker between the imidazotetrazinone 3-position and the alcohols or phenols to be released. The release of alcohol and phenol through the hydrolysis of the intermediate diazonium ions to the unstable hemiacetals that decomposed to the alcohol and phenol was confirmed by 1H NMR. The kinetics of the hydrolysis of these tetrazines in neutral aqueous solution showed a faster reaction rate compared with temozolomide (t1/2 = 0.53 and 0.36 h compared with temozolomide 1.4 h).","abstract_has_math":false,"creators":["Garelnabi, Elrashied A.E."],"institution":"University of Bradford","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Wheelhouse, Richard T."],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-08-27T15:52:17Z","date_published":"2010-08-27T15:52:17Z","updated_at":"2026-07-24T01:14:20Z","subjects":["Imidazotetrazinone prodrugs","Synthesis","Aziridinium ions","Aziridines","Drug delivery"],"languages":["en"],"rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10454/4418","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Wheelhouse, Richard T."]},{"key":"dc:creator","label":"Author","values":["Garelnabi, Elrashied A.E."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-08-27T15:52:17Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-08-27T15:52:17Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-08-27T15:52:17Z"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Institute of Cancer Therapeutics & School of Pharmacy"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Bradford"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Imidazotetrazinone prodrugs","Synthesis","Aziridinium ions","Aziridines","Drug delivery"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10454/4418"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["New imidazotetrazinones have been synthesised that possess features in their structures to release aziridinium ions upon ring opening. Unstable 2-aminoethylisocyanates were required in this preparation, which were synthesized with BOC-protection of the amino group to counteract the reactivity of the amine towards the isocyanate group in the case of aliphatic amines; in contrast, anilinoethylisocyanates were synthesized unprotected. Substituents with a range of electron-withdrawing and electron-releasing properties were introduced at the p-position of the aniline ring. A 13C-labelled study confirmed the release of the aziridinium ion by these imidazotetrazinones in neutral pH buffer solution. Furthermore the kinetics of the hydrolysis in neutral aqueous solution of some these new tetrazines were similar to temozolomide, in addition to useful acid stability. Other imidazotetrazinones were synthesised for the purpose of releasing alcohols and phenols. Their synthesis was performed with a one-carbon linker between the imidazotetrazinone 3-position and the alcohols or phenols to be released. The release of alcohol and phenol through the hydrolysis of the intermediate diazonium ions to the unstable hemiacetals that decomposed to the alcohol and phenol was confirmed by 1H NMR. The kinetics of the hydrolysis of these tetrazines in neutral aqueous solution showed a faster reaction rate compared with temozolomide (t1/2 = 0.53 and 0.36 h compared with temozolomide 1.4 h)."]},{"key":"dc:title","label":"Title","values":["New applications of Imidazotetrazinone prodrugs. Synthesis and mechanistic investigation of novel imidazotetrazinones as prodrugs of aziridines and as traceless carriers for drug delivery to the central nervous system."]}]}],"canonical_facts":{"dc:contributor.advisor":["Wheelhouse, Richard T."],"dc:creator":["Garelnabi, Elrashied A.E."],"dc:date.accessioned":["2010-08-27T15:52:17Z"],"dc:date.available":["2010-08-27T15:52:17Z"],"dc:date.issued":["2010-08-27T15:52:17Z"],"dc:description.abstract":["New imidazotetrazinones have been synthesised that possess features in their structures to release aziridinium ions upon ring opening. Unstable 2-aminoethylisocyanates were required in this preparation, which were synthesized with BOC-protection of the amino group to counteract the reactivity of the amine towards the isocyanate group in the case of aliphatic amines; in contrast, anilinoethylisocyanates were synthesized unprotected. Substituents with a range of electron-withdrawing and electron-releasing properties were introduced at the p-position of the aniline ring. A 13C-labelled study confirmed the release of the aziridinium ion by these imidazotetrazinones in neutral pH buffer solution. Furthermore the kinetics of the hydrolysis in neutral aqueous solution of some these new tetrazines were similar to temozolomide, in addition to useful acid stability. Other imidazotetrazinones were synthesised for the purpose of releasing alcohols and phenols. Their synthesis was performed with a one-carbon linker between the imidazotetrazinone 3-position and the alcohols or phenols to be released. The release of alcohol and phenol through the hydrolysis of the intermediate diazonium ions to the unstable hemiacetals that decomposed to the alcohol and phenol was confirmed by 1H NMR. The kinetics of the hydrolysis of these tetrazines in neutral aqueous solution showed a faster reaction rate compared with temozolomide (t1/2 = 0.53 and 0.36 h compared with temozolomide 1.4 h)."],"dc:identifier.uri":["http://hdl.handle.net/10454/4418"],"dc:language.iso":["en"],"dc:publisher.department":["Institute of Cancer Therapeutics & School of Pharmacy"],"dc:publisher.institution":["University of Bradford"],"dc:rights":["\"Creative
The University of Bradford theses are licenced under a Creative Commons Licence."],"dc:subject":["Imidazotetrazinone prodrugs","Synthesis","Aziridinium ions","Aziridines","Drug delivery"],"dc:title":["New applications of Imidazotetrazinone prodrugs. Synthesis and mechanistic investigation of novel imidazotetrazinones as prodrugs of aziridines and as traceless carriers for drug delivery to the central nervous system."],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["PhD"]},"updated_at":"2026-07-24T01:14:20Z"}