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Synthesis And Structure Activity Relationship Of Novel Small Molecules As Inhibitors Of Plasminogen Activator Inhibitor-1, Karl Michael Upman
Synthesis And Structure Activity Relationship Of Novel Small Molecules As Inhibitors Of Plasminogen Activator Inhibitor-1, Karl Michael Upman
Master's Theses and Doctoral Dissertations
Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) family. PAI-1 is involved in the regulation of fibrinolysis, which is the breakdown of blood clots. PAI-1 inhibits serine proteases tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), which are key factors in fibrinolysis. Excess levels of PAI-1 have also been shown to increase the risk of diabetes, stroke, and atherosclerosis, as well as tumor development. Previous attempts at synthesizing a practical drug for the regulation of PAI-1 have not been successful; therefore, it has been the purpose of this study to further advance progress …
Progress Toward A Structure-Function Relationship For Novel, Small-Molecule Inhibitors Of Plasminogen Activator Inhibitor-1, Sarah Burke
Master's Theses and Doctoral Dissertations
Plasminogen activator inhibitor-1 (PAI-1) is a serpin protein whose function is to inhibit tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and hence, fibrinolysis. This inhibition leads to decreased plasminogen to plasmin conversion, which results in deleterious effects on the organism, such as blood clots. Elevated levels of PAI-1 are implicated in a variety of diseases and conditions. We have synthesized a variety of novel, small-molecule PAI-1 inhibitors in order to establish a structure-function relationship throughout the compounds. This goal was accomplished through an iterative process in which only one aspect of the molecule was altered at a time. …
Design, Synthesis And Evaluation Of Small Molecules As Inhibitors Of Plasminogen Activator Inhibitor-1, Darshani Avanthi Weerakoon
Design, Synthesis And Evaluation Of Small Molecules As Inhibitors Of Plasminogen Activator Inhibitor-1, Darshani Avanthi Weerakoon
Master's Theses and Doctoral Dissertations
Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. Excessive levels of PAI-1 inhibit urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), which regulates fibrinolysis as well as the development of different pathological diseases like obesity, metabolic syndrome, tumor invasion and metastasis, and coronary heart disease. Currently, there is no Food and Drug Administration approval for inactivating higher levels of PAI-1. Therefore, PAI-1 is considered an attractive drug target. Due to PAI-1’s different structural conformations and multiple binding domains, development of PAI-1 inhibitors is a challenging situation. In this research study, we describe …
Structure-Activity Relationships Of Pai-1 Inhibitors, Karen Sanders
Structure-Activity Relationships Of Pai-1 Inhibitors, Karen Sanders
Master's Theses and Doctoral Dissertations
The inhibition of plasminogen activator inhibitor-1 (PAI-1) is anticipated to increase our understanding of various human ailments with which high levels of PAI-1 have been associated, including diabetes, stroke, and atherosclerosis. Previous accounts have reported the synthesis of inhibitors that bind to PAI-1 with a low affinity, inhibit the serpin plasma protein antithrombin III, and/or fail to inhibit PAI-1 when vitronectin, a cofactor of PAI-1 is present. The synthesis of small-molecule inhibitors of PAI-1 that improve upon these properties has been the main goal of this research. Research efforts focused on examining changes in inhibitor potency based on the manipulation …