Synthesis and structure activity relationship of novel small molecules as inhibitors of plasminogen activator inhibitor-1

<p>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 in this area. Working from a lead molecule derived from a high-throughput library screen, different derivatives were synthesized and tested for anti-PAI-1 activity. By studying the relationships between different aromatic substitutions, our goal was to discover a connection between these substitutions and more potent inhibition of PAI-1. This study discusses the synthesis and impact of the different derivatives of those small molecules on PAI-1 inhibition.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2016

Author dc:creator

• Upman, Karl Michael

Contributors dc:contributor

• Cory Emal, PhD, Chair
• Gregg Wilmes, PhD
• Maria Milletti, PhD

• Novel Small Molecules
• PAI-1
• Plasminogen Activator Inhibitor
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/679

OAI identifier oai:identifier

oai:commons.emich.edu:theses-2072