Medicinal-Pharmaceutical Chemistry Commons^™

Green Synthesis Of Glutethimide Intermediate Via Nash Reaction, Zahria Patrick

Undergraduate Research Symposium

The purpose of my research project is to utilize green chemistry principles to synthesize an intermediate for Glutethimide, a drug used to treat patients with insomnia. Many pharmaceutical processes require the use of halide-containing chemicals which are harmful to the environment when discarded as waste. Not only does this waste affect the quality of drinking water and aquatic life, but it affects the economy as well. The cost of waste disposal increases with the increasing difficulty of treating it and thus raises the cost of production for pharmaceutical companies.
The reaction of choice is a nucleophilic aromatic substitution of hydrogen, …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Silver-Catalyzed Synthesis Of Disubstituted Fluorinated Isoxazoles, Micah Stewart

Honors Theses

The presence of fluorine can provide organic compounds with useful biological properties, such as increased metabolic stability and drug uptake. Because of these advantages, fluorinated compounds make up about 30% of the drug industry. However, fluorination of complex molecules is difficult due to fluorine’s high electronegativity.

Fluorinated isoxazoles are of particular interest in the pharmaceutical industry. Isoxazoles are five-membered heterocycles with oxygen and nitrogen in the 1, 2 positions that are able to engage in interactions unavailable to other ring structures, conferring advantageous biological properties upon compounds containing them. However, there are limited synthetic routes for fluorinated isoxazoles, and those …

“Treat Me Covalently” – New Tools To Improve Covalent Drug Design For Advancement Of Cancer Treatments, Yuliya Mazo

Student Theses and Dissertations

The goal of this project was to investigate the complex mechanism of covalent bonding among different molecules and their targets in a modeling software ICM-Pro. Specifically, it included the identification of fundamental aspects of a covalent bonding mechanism of the Michael addition reaction. Michael addition reaction of electrophilic α, β-unsaturated carbonyl compounds with a nucleophilic cysteine residue in thymidylate synthase, papain, and EGFR tyrosine kinase were examined. Thymidylate synthase and EGFR were chosen because they are important targets in the treatment of various types of cancer. In order to find the most optimal parameters, identification and assessment of the effect …

Design And Synthesis Of Selective Estrogen Receptor Β Agonists And Their Pharmacology, K. L. Iresha Sampathi Perera

Dissertations (1934 -)

Estrogens (17β-estradiol, E2) have garnered considerable attention in influencing cognitive process in relation to phases of the menstrual cycle, aging and menopausal symptoms. However, hormone replacement therapy can have deleterious effects leading to breast and endometrial cancer, predominantly mediated by estrogen receptor-alpha (ERα) the major isoform present in the mammary gland and uterus. Further evidence supports a dominant role of estrogen receptor-beta (ERβ) for improved cognitive effects such as enhanced hippocampal signaling and memory consolidation via estrogen activated signaling cascades. Creation of the ERβ selective ligands is challenging due to high structural similarity of both receptors. Thus far, several ERβ …

Catalytic Transfer Hydrogenation Of Nitroalkenes To Primary Amines, Brendan Phillips

Chemistry Honors Papers

This work describes synthetic methodology development in organic chemistry. The goal of this work is to demonstrate new ways of making biologically-relevant molecules that are in line with the principles of green chemistry (chemical practices which seek to be, regarding human and environmental health, benign by design). To this end, a new method has been developed toward the introduction of primary amine functionalities into organic molecules from readily-available aldehydes, via reduction of nitroalkene intermediates. Traditional methods of reducing nitroalkenes to primary amines require harsh conditions, often produce stoichiometric amounts of metal salt waste, and present significant safety challenges to the …

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C² substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by ¹H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. …

Physicochemical And Structural Analysis Of Polymers As Putative Drugs, Meghan L. Thompson

Theses and Dissertations

Sulfated low molecular weight lignins (LMWLs) have shown good activity as anticoagulants by allosterically inhibiting thrombin, as well as promising agents for treating emphysema through inhibition of elastolysis, oxidation, and inflammation. Sulfated LMWLs are chemo-enzymatically synthesized from starting monomers caffeic, ferulic, and sinapic acid into sulfated dehydropolymers known as CDS, FDS, and SDS. To further the LMWLs’ development as drugs, their structural composition and physicochemical characteristics were defined in this work. The molecular weight distribution profile of the sulfated LMWLs from size exclusion chromatography performed on a high pressure liquid chromatography system (SEC-HPLC) changed from bimodal when no surfactant is …