Medicinal Chemistry Dissertations and Theses: Recent submissions
Now showing items 21-40 of 80
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Structural and Functional Evaluation of Steroidogenic Cytochrome P450 Enzymes
(University of Kansas, 2015-08-31)Cytochromes P450 (CYP450) are heme-containing monooxygenase enzymes that perform a variety of functions in humans, including xenobiotic metabolism and the production of endogenous signaling molecules. Six isoforms of ... -
Exploration of Toll-like Receptor 7 and 8 Agonists as Potential Vaccine Adjuvants
(University of Kansas, 2015-05-31)Toll-like receptors (TLRs)-7/-8 are among pathogen recognition receptors (PRRs) present in the endosomal compartment that are activated by viral single-stranded RNA (ssRNA) as well as synthetic small molecules. TLR7/8 ... -
Inhibition of Heat Shock Protein 90 Machinery for the Treatment of Cancer: Progress in the Development of Alternative Strategies
(University of Kansas, 2015-05-31)Heat shock proteins (Hsps) are molecular chaperones that facilitate the conformational maturation of newly synthesized and unfolded cellular proteins (termed “clients”) to maintain protein homeostasis. Heat shock protein ... -
Assessing ADME properties of CJ-15,208: synthesis of new analogs and examination of P-glycoprotein interactions
(University of Kansas, 2015-12-31)We are exploring analogs of the macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) as both potential analgesics and kappa opioid receptor (KOPr) antagonists. KOPr agonists exhibit analgesic ... -
Stereodivergent Synthesis of Enantioenriched Five- and Six-Membered Cyclic-1,3-diols and Applications Toward Library Synthesis
(University of Kansas, 2015-12-31)Abstract This work describes the development of methods to access synthetically useful chiral diols in enantiomerically pure form. First chapter describes the development of a stereodivergent approach for enantioenriched ... -
Studies and Synthetic Methodology: 1. Cycloaddition of Allylic Azides and Alkynes, 2. Hexafluoro-2-propanol-promoted Friedel–Crafts Acylation Reactions
(University of Kansas, 2016-08-31)Cycloaddition of allylic azides and alkynes. The 1,3-dipolar Huisgen azide-alkyne cycloaddition is a significant area of interest in modern chemistry. The use of allylic azides as dynamic reaction partners represent a novel ... -
Structure-Based Design of Grp94-Selective Inhibitors
(University of Kansas, 2014-12-31)Heat shock protein 90 KDa (Hsp90) belongs to family of proteins called molecular chaperone that are associated with protein folding and maturation. Hsp90 clients play a critical role in the pathogenesis of diseases such ... -
I. Selective Probes for Cytochrome P450 17A1 Suggest a Design Strategy Toward Improved Breast and Prostate Cancer Agents II. Spatiotemporal Control of Reactivity via Visible Light-Mediated C-H Activation Creates Patterned Carbohydrate Surfaces III. Toward Catalytic Intramolecular Schmidt Reactions
(University of Kansas, 2014-12-31)Selective Probes for Cytochrome P450 17A1 Suggest a Design Strategy Toward Improved Breast and Prostate Cancer Agents. Sex steroids stimulate the growth of hormone-responsive breast and prostate tumors, the two most commonly ... -
Synthetic Molecular Probes of Endocytosis, Escape from Endosomes, and Protein-Protein Interactions
(University of Kansas, 2014-08-31)Over the past several years, the Peterson group has developed synthetic mimics of cholesterol that rapidly incorporate into the plasma membrane of mammalian cells. These N-alkyl-3&beta-cholesterylamines cycle between the ... -
A Serine-Derived Butenolide as a Versatile Chiral Building Block: Applications in the Synthesis of Natural and Nature-Like Compounds of Biological Significance
(University of Kansas, 2014-05-31)Part I. HIV Protease Targeted Synthesis of Conformationally–Rigid Hydroxyethylene Dipeptide Isosteres: A Combinatorial approach With the success of Highly Active Anti-Retro Viral therapy (HAART), the life expectancy ... -
I. Catalysis of Intra- and Intermolecular Schmidt Reactions. II. Copper-Catalyzed Oxaziridine-Mediated C-H Bond Oxidation. III. Synthesis and Cytotoxic Evaluation of Withalongolide A Analogues.
(University of Kansas, 2014-05-31)The research presented herein describes four separate projects, focusing on synthetic methodology development, discovery of novel cytotoxic agents, and natural product isolation. Catalysis of Intra- and Intermolecular ... -
Design, Synthesis and Biological Evaluation of Ring-constrained and Biphenyl Derivatives as Hsp90 C-terminal Inhibitors
(University of Kansas, 2014-05-31)Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that plays a pivotal role in protein homeostasis in responses to cellular stress. Hsp90 regulates the conformational maturation, activation, and integrity ... -
Synthetic delivery systems that control release of anticancer agents from early endosomes
(University of Kansas, 2013-12-31)Tubulin-binding agents are an important class of therapeutics for cancer chemotherapy. However, their application can be limited by systemic toxicity, poor tissue specificity, and drug resistance. To address these issues, ... -
Design and Synthesis of Novel CNS Biological Probes
(University of Kansas, 2013-12-31)Agents that exert their effects in the central nervous system are among the most important in medicinal practice. One in three Americans will have a disease affecting the nervous system in their lifetime exceeding $600 ... -
Investigations Of Salvinorin A: Synthetic Isolation, Quantification, And In Vivo Characteristics
(University of Kansas, 2013-05-31)While many ligands are known to interact with the opioid receptor system, most can be traced back to the common morphine scaffold. In several cases ligands have been developed that are selective for either the mu, kappa, ... -
Synthesis and biological evaluation of dynorphin analogs and, Caco-2 permeability of opioid macrocyclic tetrapeptides
(University of Kansas, 2013-08-31)We are interested in the development of potent and highly selective dynorphin (Dyn) analogs targeting kappa opioid receptors (KOR) and studying the pharmacokinetic and physicochemical properties of kappa opioid peptides. ... -
A Combined Allylic Azide Rearrangement and Intramolecular Schmidt Reaction - Discovery, Development, and Application
(University of Kansas, 2012-12-31)The research presented herein describes synthetic applications of an allylic azide rearrangement, mainly focusing on its combination with the intramolecular Schmidt reaction to afford vinyl-substituted bicyclic lactams. ... -
CYTOCHROMES P450 AS THERAPEUTIC TARGETS AND COUNTER-TARGETS FOR THE PREVENTION OF LUNG CANCER AND TREATMENT OF STEROIDOGENIC DISEASES
(University of Kansas, 2012-05-31)Cytochrome P450 (CYP) is a superfamily of heme-containing monooxygenase enzymes that metabolize a variety of endogenous and exogenous substrates. These transformations can be advantageous in the role of homeostasis or ... -
Cytochromes P450: Inhibition of CYP2A Enzymes Involved in Xenobiotic Metabolism and Generation of CYP26 Enzymes Involved in Retinoic Acid Metabolism
(University of Kansas, 2012-08-31)The cytochrome P450 (P450) superfamily of mixed function oxidase enzymes catalyze the metabolism of a variety of endogenous and exogenous biochemicals, including steroids, fatty acids, vitamins, eicosanoids, drugs, pesticides, ... -
Investigation of the Hsp90 C-terminal Binding Site, Novel Inhibitors and Isoform-Dependent Client Proteins
(University of Kansas, 2012-08-31)The heat shock proteins represent an important class of pro-survival proteins that are intimately involved in cell survival, adaptation to cellular stress, and protein management. Heat shock protein 90 kDa (Hsp90) is a ...