Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 49 for “"metabolic stability"”.
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Prediction of Metabolic Stability and Bioavailability with Bioisosteric Replacements
… trials due to numerous issues, including metabolic stability and efficacy issues, wasting years of research effort and resource. This thesis detailed the development of in silico methods to predict the metabolic stability of structures and their bioavailability. Coralie Atom-based …
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Metabolic Stability And Pharmacokinetics In Lead Optimization Of Potential Anti-Psychostimulant Pharmacotherapies
… analogs were then synthesized by blocking the metabolic soft spots of CM156. We performed a preliminary screening of a series of the high affinity sigma receptor antagonists using in vitro metabolism studies and selected AZ66, 3-(4-(4-cyclohexylpiperazine-1-yl)pentyl)-6-fluorobenzo[ d]thiazole …
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Design, Synthesis, Biological Evaluation and Metabolic Stability Studies of Sigma Receptor Ligands
… goal of this project was to conduct microsomal stability studies on some promising sigma receptor analogues. The data gathered from the pharmacokinetic studies has provided valuable information towards the mechanism of biotransformation of this class of sigma ligands. This knowledge is helpful …
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Synthesis and biological evaluation of novel small molecule bromodomain inhibitors
… suboptimal resulting in reduced potency and poor metabolic stability (Figure 0.1). However, substitution of the six-membered ring and increasing the steric hindrance of the pyridyl core resulted in compounds with low microsomal and hepatocyte clearance (Figure 0.1). A lead molecule was identified …
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Synthesis, physicochemical and biological evaluation of N-dealkylated metabolites of antimalarial pyrido[1,2-a]benzimidazoles and related compounds containing a Mannich base side-chain
… solubility, cytotoxicity, and microsomal metabolic stability in mouse liver microsomes were evaluated. To investigate structure activity relationships (SARs), the study was broadly diversified into two series (SAR-1 and SAR-2). Mannich base side-chains from SAR-1 were designed and …
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Storage and mobilization of nitrogen in the peach tree / by B.K. Taylor.
… investigated in this thesis. In addition, the metabolic stability of constituents of the storage nitrogen of dormant peach trees was studied.
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A Pharmacokinetics and Pharmacodynamics (PK/PD) Guided Approach to Lead Optimization of Nitrofuranylamide Anti-Tuberculosis Agents
… observations were further supported by the poor metabolic stability of Lee 562. Thus, two second generation follow-up compounds, Lee 878 and Lee 952 were tested that included structural modifications for increased metabolic stability. Both compounds showed improved metabolic stability compared to …
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Synthesis, pharmacological and physicochemical profiling of antimalarial and antischistosomal N-aryl 3-trifluoromethyl pyrido [1,2-α] benzimidazoles
… and pharmacokinetics assessment, including metabolic stability and cytotoxicity against Chinese hamster ovarian cell lines. Representative compounds were evaluated for their interaction potential with the human ether-a-go-go-related gene (hERG), a potassium ion channel whose inhibition can …
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Synthesis, pharmacological and solubility evaluation of antiplasmodial pyrido[1,2-a]benzimidazoles with cyclic and functionalized amine side chain substituents
… or improving antiplasmodial activity and metabolic stability. Aminopiperidine-based compounds were found to possess the most potent antiplasmodial and beta-hematin inhibition activity coupled with moderate to high turbidimetric solubility. Analogues with pyrrolidine and piperazine groups …
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Development of Small Molecules as Broad-spectrum Filoviral Entry Inhibitors
… a pseudovirus assay. Selectivity, potency, and metabolic stability of these viral entry inhibitors were improved by introducing structural modifications. In addition, antiviral activity was validated using replication-competent EBOV and MARV, mutational analysis was used to identify the …
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Design, synthesis, and structure-activity relationship studies of dual Plasmodium falciparum phosphatidylinositol 4-kinase and cGMP-dependent protein kinase inhibitors
… gene (hERG) activity (IC50 > 10 µM) and high metabolic stability against human, rat, and mouse (H/R/M) liver microsomes (> 75% remaining after 30-min incubation). Selected compounds from the series also showed the potential for transmission blockade with specificity for stage IV/V gametocytes …
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A Survey of Stapling Methods to Increase the Affinity, Activity and Stability of Ghrelin Analogues
… it proteolytically unstable. This inherent instability in ghrelin can be overcome by incorporating helix-inducing staples that stabilize its structure and improve affinity and activity. We present an analysis of different stapling methods at positions 12 and 16 of ghrelin(1-20) analogues with …
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A Structure-Activity Relationship Study of Dihydroajoenes as Anti-Cancer Agents
… the double bond on biological activity and metabolic stability, since ajoenes are unstable in blood. A divergent synthetic route to 6 new dihydroajoene analogues has been developed in which a phenolic hydroxyl group at the disulfide end served as a platform for modulating aqueous solubility. …
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Synthesis and evaluation of benzoyl containing compounds as potential anti-cancer agents
… of a human body, pharmacological factors such as stability within plasma and metabolic stability were measured. These are responsible for measuring the degradation of the compound over time and looking at the ability of the liver to remove the administered drug respectively. The data was collected …
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Synthesis, biological activity and physicochemical properties evaluation of antiplasmodial pyrimido[1,2-a]benzimidazoles
… and for selected compounds, microsomal metabolic stability, were also evaluated. The most potent compounds against the asexual blood stage (ABS) parasites belonged to SAR3 series with the most active derivative being 19 (IC50 (PfNF54) = 0.156 μM), which combined the electron-withdrawing …
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Approaches for the Implementation of Sustainability along the Pharmaceutical Life Cycle
… are designed for efficacy at low doses and metabolic stability, these properties cause environmental harm and persistence. Sustainable pharmacy requires addressing environmental, societal, and economic sustainability across the pharmaceutical life cycle. As few German research groups work on …
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Tuning strength and specificity in the N-end rule
… of a protein's N-terminal residue determines its metabolic stability. In E. coli, CIpAP is the principal protease that degrades proteins bearing an N-terminal phenylalanine, tyrosine, tryptophan, or leucine residue. The CIpS adaptor, which displays homology to eukaryotic ubiquitin ligases that …
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Exploiting Chemical Libraries to Identify and Characterize Novel Bioactives with Efficacy Against Pathogenic Candida Species
… valine at this position are resistant. The poor metabolic profile of NP-BTA prompted us to assess the efficacy of this molecule in a mouse skin model of dermatomycosis. Finally, I engaged in a collaborative program to optimize inhibitors of the fungal casein kinase, Yck2. An existing Yck2 …
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Development of Novel Small-Molecule Therapeutics for Multiple Sclerosis
… aim of improving the pharmacokinetics and metabolic stability of these molecules. Chapter 6 concludes the thesis by discussing knowledge gained throughout and provides a perspective on future research directions. In the end, this thesis provides ‘drug-like’ molecular tools and assesses the …
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Metabolic Profiling of Prions In The Gastro-Intestinal Tract
<p><strong>Metabolic profiling of prions in the gastro-intestinal tract</strong><strong></strong></p> <p><strong>Uffaf Khan, B.S.</strong></p> <p><strong>Thesis Advisor: Claudio Soto, Ph.D.</strong></p> <p><strong>Abstract</strong></p> <p>Prion diseases, also known as transmissible spongiform …
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