Medicinal Chemistry Dissertations and Theses: Recent submissions
Now showing items 61-80 of 80
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Nucleophilic Additions to 3-Azido-hexanal
(University of Kansas, 2009-04-29)Sakurai and Mukaiyama aldol additions were carried out with 3-Azido-hexanal under chelation and non-chelation conditions. The reactions were generally found to be diastereofacially selective in favor of the anti stereoisomer ... -
DESIGN, SYNTHESIS AND METABOLISM OF ARODYN ANALOGS
(University of Kansas, 2009-01-22)Our research focuses on the development of kappa opioid receptor (KOR) antagonists. KOR antagonists have a variety of possible therapeutic applications; these compounds have shown anxiolytic activity, anti-depressive ... -
Synthesis and Reactivity of Medium-Bridged Twisted Lactams
(University of Kansas, 2009-10-08)The research presented herein describes the development of synthetic methods to one-carbon bridged twisted amides and the study of properties of one-carbon bridged lactams. Initial investigations focused on electrostatic ... -
Development of Three Reaction Methodologies En Route to Nitrogen Containing Heterocycles: a Diels-Alder/Schmidt, a DIels-Alder/Acylation and a Catalytic Intramolecular Schmidt
(University of Kansas, 2009-09-29)This thesis describes three new advances in the synthesis of nitrogen containing heterocycles. The first two chapters discuss the development of two different domino reaction sequences: a Diels-Alder/Schmidt and a ... -
Studies on Oximidine II - Total Synthesis by an Unprecedented Reductive Coupling
(University of Kansas, 2009-10-20)The benzolactone enamide natural products are identified by three structural characteristics: a salicylate arene, a 12- or 15-membered macrolactone, and an enamide side chain. These natural products exert their biological ... -
Synthesis and evaluation of modified oximidine analogues as anticancer agents and of terephthalaldehyde-bis-guanylhydrazones as endotoxin sequestering agents
(University of Kansas, 2009-12-15)Part I. The natural products oximidine I and II are potent and selective anticancer agents at nanomolar concentrations. Their structures and potent cytotoxicity are similar to the recently discovered natural products ... -
Iron-catalyzed decarboxylative cross coupling reactions and palladium-catalyzed sp2-sp3 coupling of coumarins.
(University of Kansas, 2009-12-15)The thesis details the development of a decarboxylative synthesis of aryl ethers using a relatively new Iron catalyst and a novel decarboxylative coupling of coumarins catalyzed by palladium. Aryl allyl carbonates underwent ... -
Natural Product Inhibitors of Hsp90: Potential Leads for Drug Discovery
(University of Kansas, 2009-07-09)This thesis represents a discussion of the advancements made in the area of Hsp90 therapeutics, and the development of a novel Hsp90 inhibitory scaffold of natural product origin. Through utilization of a recently reported ... -
Design, Synthesis and Evaluation of Peptide-Based Affinity Labels for Mu Opioid Receptors
(University of Kansas, 2009-07-17)Narcotic analgesics produce pain relief generally through activation of &mu opioid receptors (MOR), but the use of these analgesics is limited by their side effects, namely respiratory depression, tolerance, physical ... -
Vinylogous Esters and Amides: Useful Synthons for Diversity-Oriented and Natural Product Synthesis
(University of Kansas, 2009-05-04)The first total synthesis of boehmeriasin A was achieved in seven steps from readily available materials with an overall yield of 29%. The absolute stereochemistry of the natural product was determined to be of the ... -
Design and Synthesis of Novel Linear and Cyclic Peptide Ligands for Kappa Opioid Receptors
(University of Kansas, 2008-09-04)Our research focuses on the development of potent and highly selective peptide ligands for kappa (κ) opioid receptors and examination of the structure-activity relationships (SAR) for activity at these receptors. Both κ ... -
The human cytochrome P450 2A family: Comparisons and identification of amino acids essential for substrate recognition
(University of Kansas, 2008-01-01)The goal of this research was to identify the differential structure-activity relationships between cytochromes P450 (CYP) 2A13 and 2A6 and their substrates. Cytochromes P450 2A13 and 2A6 are very closely related, having ... -
Novel Intramolecular Nucleophilic Addition Reactions: Formation of Unusual N-O-Heterocyclic Enones
(University of Kansas, 2008-09-04)Novel Intramolecular Nucleophilic Addition Reactions: Formation of unusual N-O-Heterocyclic Enones Adwait R. Ranade, B. Tech. The University of Kansas, 2008 Cyclic enaminones, which possess vinylogous amide functionality ... -
Synthetic and computational efforts toward the understanding and development of novobiocin-derived inhibitors of Hsp90
(University of Kansas, 2008-01-01)As C−terminal inhibitors of a 90−kDa heat shock protein (Hsp90), novobiocin and its derivatives are a significant part of an emerging class of cancer chemotherapeutic agents. Previous studies have shown that ... -
The Application of X-ray Crystallography towards the Design of Novel Inhibitors of MurA and CDK2
(University of Kansas, 2008-10-23)Infectious diseases and cancers are the second and third largest causes of death worldwide. UDP-N-acetyl-glucosamine (UNAG) enolpyruvyl transferase (MurA)and Cyclin-dependent kinases (CDKs) are proven as antibiotic and ... -
Development of a Parallel Strategy for the Synthesis of a Library of 2-(3-Formyl-5-arylfuran-2-yl)ethylcarbamates from Dihydropyridinones
(University of Kansas, 2008-09-09)2,3-Dihydropyridin-4(1H)-ones were utilized as scaffolds for the syntheses of libraries of 5-arylethynyl-2,3-dihydropyridin-4(1H)-ones and 2-(3-formyl-5-arylfuran-2-yl)ethylcarbamates. 2,3-Dihydropyridin-4(1H)-ones were ... -
Isatin Derivatives as Inhibitors of Microtubule Assembly
(University of Kansas, 2008-09-04)This thesis describes the rationale, design, and syntheses of derivatives of isatin (1-H-indole-2,3-dione). Isatin was identified, during a high throughput screen of 10,000 compounds, as a potential scaffold for ... -
Human Cytochrome P450 2E1: Functional Comparison to Cytochrome 2A13 and 2A6
(University of Kansas, 2008-05-05)The cytochrome P450 (CYP) superfamily of enzymes plays the predominant role in human phase I xenobiotic metabolism. The CYP2 family, in particular, is known for it extensive Phase I metabolism of a majority of the xenobiotic ... -
Design, Syntheses, and Evaluation of Lipopolyamines as Anti-Endotoxin Agents
(University of Kansas, 2007-12-19)Endotoxins, or Lipopolysaccharides (LPS) present on the surface of Gram negative bacteria play a key role in the pathogenesis of septic shock, a common clinical problem and a leading cause of mortality in critically ill ... -
Probing the Antibiotic Target MurA from S. aureus and B. subtilis
(University of Kansas, 2007-12-18)MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) catalyzes the first committed step in the biosynthesis of cell wall peptidoglycan. Because this pathway is absent in mammals, MurA is an attractive target for the ...