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dc.contributor.advisorO'Hagan, David
dc.contributor.authorAbdul Manan, Mohd Abdul Fatah
dc.coverage.spatialxvi, 223 p.en_US
dc.description.abstractChapter 1 provides a general introduction on the role of bioisosterism of fluorine aiming to improve the pharmacokinetics properties of lead compounds. GABAA receptors specifically, synaptic GABAA receptors, extrasynaptic GABAA receptors and GABAA rho receptors are then presented. Compounds that exhibit agonist and partial agonist effects at these receptors are also discussed. The applications of some compounds as GABAA receptor PET radiotracers are also described. Chapter 2 details the synthesis of two fluorinated analogues of muscimol, fluoromuscimol and trifluoromethylmuscimol. Fluoromuscimol was obtained from the lithiation of a Boc-protected isoxazole followed by in-situ fluorination using NFSI, whereas trilfuoromethylmuscimol was obtained from the coupling of a heteroaryl iodide with trifluoromethylcopper species, which was generated in-situ from MFSDA in the presence of CuI. Fluoromuscimol and trifluoromethylmuscimol were assessed on human synaptic, (α₁β₂γ₂), extrasynaptic, (α₄β₂δ) and ρ₁ subunits of the GABAA receptor. The biological results show that fluoromuscimol exhibits greater maximum response in comparison to GABA at the extrasynaptic GABAA receptors (α₄β₂δ), but lower overall potency, whereas trifluoromethylmuscimol was inactive at all the tested GABAA receptors. Chapter 3 discusses the synthesis and late stage fluorination of diaryliodonium salts as precursors to fluoromuscimol. Application of iodonium salts as precursors for nucleophilic fluorination in PET studies are also highlighted. The last part of this chapter focuses on the synthesis of iodomuscimol as a potential alternative SPECT radiotracer to fluoromuscimols in probing GABA binding sites on GABAA receptors.en_US
dc.publisherUniversity of St Andrews
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.subjectGABA agonistsen_US
dc.subjectGABA receptors fluorinationen_US
dc.subject.lcshOrganofluorine compoundsen
dc.subject.lcshOrganofluorine compounds--Synthesisen
dc.titleFirst syntheses of fluoromuscimolsen_US
dc.contributor.sponsorMalaysia. Ministry of Educationen_US
dc.contributor.sponsorUniversiti Teknologi MARAen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US

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