Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin family of proteins, a primary inhibitor of both tissue-type and urokinase-type plasminogen activators in plasma, and is a well-established risk factor in various disease conditions. Increased levels of active PAI-1 in plasma are correlated with the development of atherosclerosis, diabetes, stroke, and other maladies. In the present study, we describe the synthesis of two new series of compounds that aim to reduce physiologically active PAI-1 levels. These molecules are related to a series of bis-arylsulfonimides and arylsulfonamides connected by short linking diamines, and to a series of hydrazine-based analogues. These studies resulted in the identification of small molecule inhibitors of PAI-1 that displayed in vitro IC50 values in the low micromolar range.
","abstract_html":"<p>Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin family of proteins, a primary inhibitor of both tissue-type and urokinase-type plasminogen activators in plasma, and is a well-established risk factor in various disease conditions. Increased levels of active PAI-1 in plasma are correlated with the development of atherosclerosis, diabetes, stroke, and other maladies. In the present study, we describe the synthesis of two new series of compounds that aim to reduce physiologically active PAI-1 levels. These molecules are related to a series of bis-arylsulfonimides and arylsulfonamides connected by short linking diamines, and to a series of hydrazine-based analogues. These studies resulted in the identification of small molecule inhibitors of PAI-1 that displayed <em>in vitro</em> IC<sub>50</sub> values in the low micromolar range.</p>","abstract_has_math":false,"creators":["Anumala, Himabindu"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Open Access Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Cory Emal, PhD, Chair","Gregg Wilmes, PhD","Steven Pernecky, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-03-15T07:00:00Z","date_published":"2014-03-15T07:00:00Z","updated_at":"2026-07-24T02:17:06Z","subjects":["Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.emich.edu/theses/701","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cory Emal, PhD, Chair","Gregg Wilmes, PhD","Steven Pernecky, PhD"]},{"key":"dc:creator","label":"Author","values":["Anumala, Himabindu"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2017-07-12T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.emich.edu/theses/701"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin family of proteins, a primary inhibitor of both tissue-type and urokinase-type plasminogen activators in plasma, and is a well-established risk factor in various disease conditions. Increased levels of active PAI-1 in plasma are correlated with the development of atherosclerosis, diabetes, stroke, and other maladies. In the present study, we describe the synthesis of two new series of compounds that aim to reduce physiologically active PAI-1 levels. These molecules are related to a series of bis-arylsulfonimides and arylsulfonamides connected by short linking diamines, and to a series of hydrazine-based analogues. These studies resulted in the identification of small molecule inhibitors of PAI-1 that displayed in vitro IC50 values in the low micromolar range.
"]},{"key":"dc:title","label":"Title","values":["Design, synthesis, and biological evaluation of non-symmetric smal"]}]}],"canonical_facts":{"dc:contributor":["Cory Emal, PhD, Chair","Gregg Wilmes, PhD","Steven Pernecky, PhD"],"dc:creator":["Anumala, Himabindu"],"dc:date.available":["2017-07-12T07:00:00Z"],"dc:description.abstract":["Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin family of proteins, a primary inhibitor of both tissue-type and urokinase-type plasminogen activators in plasma, and is a well-established risk factor in various disease conditions. Increased levels of active PAI-1 in plasma are correlated with the development of atherosclerosis, diabetes, stroke, and other maladies. In the present study, we describe the synthesis of two new series of compounds that aim to reduce physiologically active PAI-1 levels. These molecules are related to a series of bis-arylsulfonimides and arylsulfonamides connected by short linking diamines, and to a series of hydrazine-based analogues. These studies resulted in the identification of small molecule inhibitors of PAI-1 that displayed in vitro IC50 values in the low micromolar range.
"],"dc:identifier":["https://commons.emich.edu/theses/701"],"dc:subject":["Chemistry"],"dc:title":["Design, synthesis, and biological evaluation of non-symmetric smal"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Open Access Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T02:17:06Z"}