The synthesis of heterocyclic systems for use in biological imaging

QD Chemistry

Gilfillan, Lynne ; Sutherland, Andrew

University:University of Glasgow

Department:School of Chemistry

关键词: QD Chemistry;   

Others  :  http://theses.gla.ac.uk/4745/1/2013Gilfillanphd.pdf

来源: University of Glasgow

【 摘 要 】

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 synthesisof 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. Thefluorescence properties of these compounds were then investigated which revealed the naphthalene and nitrophenyl substituted analogues to be fluorescent and thus havepotential to be used as peptide labels for fluorescence imaging.