Polycyclic Compounds Commons^™

Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, Hari K. Akula

Dissertations, Theses, and Capstone Projects

The C4 amide carbonyl of O-t-butyldimethylsilyl-protected thymidine, 2’-deoxyuridine, and 3’-azidothymidine (AZT) was activated by reaction with (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF as solvent. This led to the formation of corresponding O⁴-(benzotriazol-1-yl) derivatives, which are reactive intermediates. Substitution at the C4 position was then carried out by reactions with alkyl and aryl amines, and thiols. Typically, reactions were conducted as a two-step, one-pot transformation, and also as a one-step conversion. After examining the reactions, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang

Pharmacy Faculty Articles and Research

Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2',3'-dideoxy-5-fluoro-3'- thiacytidine (FTC), and 2',3'-dideoxy-3'-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides.

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

What Is New For An Old Molecule? Systematic Review And Recommendations On The Use Of Resveratrol, Ole Vang, Nihal Ahmad, Karen Brown, Anna Csiszar, Thomas Szekeres, Thomas Walle, Joseph M. Wu

NYMC Faculty Publications

BACKGROUND: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.

METHODOLOGY: Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of …

Synthesis Of Nucleoside 5′-O-Α,Β-Methylene-Β-Triphosphates And Evaluation Of Their Potency Towards Inhibition Of Hiv-1 Reverse Transcriptase, Yousef Ahmadibeni, Chandravanu Dash, M. J. Hanley, S. F. J. Le Grice, Hitesh K. Agarwal, Keykavous Parang

Pharmacy Faculty Articles and Research

A polymer-bound α,β-methylene-β-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5′-O-α,β-methylene-β-triphosphates. Among all the compounds, cytidine 5′-O-α,β-methylene-β-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a Ki value of 225 μM.