This work is part of a wider ongoing collaborative program, involving expertise from within the University of Bristol. It has predominantly involved the development of novel small molecules with the potential to treat Alzheimer's disease, by targeting the extracellular domain of the kinase receptor, TrkA. TrkA binders can act as agonists, with the possibility to treat Alzheimer's disease or as antagonists with the ability to treat inflammatory pain. A novel family of antagonist compounds, based around methoxyphenyl 25 have been synthesised. This parent compound was prepared using reductive amination and had an ICso value of 20 IlM on an in-house radioligand competition binding assay. The lH_1SN HSQC protein NMR spectra of 25 with the TrkA protein showed peak shifts which indicate binding to the same region as the endogenous ligand (nerve growth factor).
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:651311 |
| Date | January 2011 |
| Creators | Hemmings, Jennifer L. |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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