Myerson, Richard James (2017). The development of novel allosteric modulators of the 5-HT3A receptor. University of Birmingham. Ph.D.
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Myerson17PhD.pdf
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Abstract
This thesis reports the Structure Activity Relationship study that was performed upon the 5-substituted-indole core as a means to identify Negative Allosteric Modulators of the human 5-HT3A receptor for the development of potential drugs for the treatment of IBS-d. Herein is reported the successful identification of a PAM to NAM switch and three novel NAMs which provide the basis for further study into the treatment of IBS-d and insight into the identity of the allosteric site of the human 5-HT3A receptor. The design, synthesis and testing of a novel fluorescent analogue of the orthosteric antagonist Quipazine is also described for the application of an improved competitive binding experiment without the need for radio-labelled ligands. Furthermore, the design and synthesis of novel diazirinyl-indoles for photo-affinity binding studies towards the identification of the allosteric site of the 5-HT3A receptor. Finally, the design and synthesis of novel BODIPY-BAPTA based fluorescent PET sensors for the detection of larger than usual ranges in concentration of cellular Ca2+ levels are described.
Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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Award Type: | Doctorates > Ph.D. | |||||||||
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College/Faculty: | Colleges (2008 onwards) > College of Engineering & Physical Sciences | |||||||||
School or Department: | School of Chemistry | |||||||||
Funders: | None/not applicable | |||||||||
Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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URI: | http://etheses.bham.ac.uk/id/eprint/7657 |
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