The synthesis of heterocyclic systems for use in biological imaging

Gilfillan, Lynne (2013) The synthesis of heterocyclic systems for use in biological imaging. PhD thesis, University of Glasgow.

Abstract

The first research project described in this thesis is the development of new SPECT and PET imaging agents for group II metabotropic glutamate receptors (mGluR2/3). Investigation of these receptors is of great interest as they have been implicated in many psychiatric disorders. A small library of 1,5-benzodiazepinones were synthesised with potential radiolabelling sites incorporated in the 7- and 8-positions around the benzodiazepinone core. Once synthesised the binding affinity of the compounds with mGluR2 was determined using the [35S]GTPγS binding assay, which revealed them to be highly potent. Physicochemical properties were also investigated to determine whether compounds were likely to be brain penetrant. The 8-trifluoromethyl-7-methoxy and 8-iodo substituted compounds were found to have the required properties to be progressed. Work then focused on the synthesis of radiolabelling precursors of the hit compounds.

The second research project outlined in thesis involves the synthesis of novel heterocycle containing α-amino acids. Previous work in the Sutherland group achieved the synthesis
of enone containing amino acids from L-aspartic acid. Building upon this, such enones were employed to form a small library of phenylpyrazole containing amino acids. The
fluorescence properties of these compounds were then investigated which revealed the naphthalene and nitrophenyl substituted analogues to be fluorescent and thus have
potential to be used as peptide labels for fluorescence imaging.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Sutherland, Dr. Andrew
• Date of Award: 2013
• Depositing User: Miss Lynne Gilfillan
• Unique ID: glathesis:2013-4745
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 Jan 2014 09:11
• Last Modified: 17 Jan 2014 09:29
• URI: https://theses.gla.ac.uk/id/eprint/4745