ABSTRACT
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor, which plays a pivotal part in the development of the central nervous system. Aberrant expression of full-length ALK occurs in neuroblastoma and chromosomal translocation or inversion of the ALK gene can generate novel fusion-ALK proteins that possess constitutive kinase activity and contribute to oncogenic processes. One of the well-studied fusion proteins is nucleophosmin (NPM-ALK), which draws a lot of attention for medicinal chemists to design small molecules as kinase inhibitors for this target. In this dissertation, [1, 2, 4]-Dihydrotriazine dimers as competitors of the lead compound NVP-TAE684 targeting NPM-ALK have been designed and synthesized. Molecular modelling studies show that those dihydrotriazine dimers have a great potential to be better kinase inhibitors.
Chapter two describes imaging in the drug discovery and development arena. One of important imaging techniques is positron emission tomography (PET). PET is a radionuclide based molecular imaging technique, which can be used for early detection, characterization, "real time" monitoring of diseases, and investigation of the efficacy of drugs. Fluorine-18 (18F) based molecular probes for PET imaging still remain big challenging to prepare but have gained increased interest by radiochemists in the past two decades. In this study, a novel approach to introduce fluorine into a molecular probe has been discovered based on boron chemistry. A few novel fluorine capture reagents have been synthesized and described in this Chapter.
| Identifer | oai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-6535 |
| Date | 02 July 2014 |
| Creators | Zhou, Fenger |
| Publisher | Scholar Commons |
| Source Sets | University of South Flordia |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Graduate Theses and Dissertations |
| Rights | default |
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