Heterocyclic Compounds Commons^™

Method Development Of [3 + 2] Cycloadditions Using Tertiary Amine N-Oxides And Efforts Towards The First Total Synthesis Of Chrysosporazine D, Alexander Cocolas

Electronic Theses and Dissertations

Nitrogen-containing heterocycles are ubiquitous in bioactive molecules, pharmaceutical drugs, and natural products. For this reason, finding new and efficient ways to make such compounds remains a high priority for the organic and medicinal community. Our current endeavors build upon previously established work by our group, where we generated 1,2-diamines by coupling commercially available aldehydes with trimethylamine N-oxide (TMAO) in two steps. This route proved to be effective in generating 20+ novel 1,2-diamines and imidazolidines with a demonstrated ability to undergo transformations. Using this chemistry, we have developed a diastereoselective synthesis of 50+ novel 7-azanorbornanes using tertiary amine N-oxides …

Heterocyclic Amines And Arylamine N-Acetyltransferase 2 Polymorphism In Pathogenesis Of Insulin Resistance., Kennedy M. Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are formed when cooking meats at high temperatures or for long periods of time, and their major metabolic pathway includes hepatic N‑hydroxylation by CYP1A2 followed by O-acetylation by N-acetyltransferase 2 (NAT2). NAT2 is a highly polymorphic gene involved in metabolism of drugs and xenobiotics, and its single nucleotide polymorphisms (SNPs) produce phenotypes characterized as slow, intermediate, or rapid acetylator. Recent studies have documented associations between HCAs and insulin resistance and between certain NAT2 phenotypes and insulin resistance. In this study, we demonstrated that NAT2 activity and exposure to certain HCAs may alter cellular glucose …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …