Stereocontrolled Synthesis and Evaluation of Platelet Aggregation Inhibitory Activity of Highly Decorated Lactam Carboxamides

Document Type

Poster

Event Website

https://source2022.sched.com/

Start Date

16-5-2022

End Date

16-5-2022

Keywords

Sustainability, Pharmaceuticals, Antithrombotic, Synthesis

Abstract

The most common causes of mortality worldwide are currently heart attacks and strokes. They result from significant clotting of blood in the arteries. This is commonly referred to as arterial thrombosis. The search for more selective antithrombotic agents therefore represents an important research objective. One lactam carboxamide (a cyclic amide that bears a noncyclic amide functional group) has recently been found to exhibit remarkable efficacy in reducing arterial thrombosis in mouse models. It outperformed the standard drug, aspirin. In these studies, a diverse library of lactam carboxamides has been assembled in a cost-effective, atom-economical, and orientation-specific manner by utilizing green chemistry. This method used to create the library is modular, chemoselective, and diastereoselective. This provides an excellent opportunity for further therapeutic applications. The structures of the synthesized carboxamides have been confirmed by routine spectroscopic techniques, including nuclear magnetic resonance spectrometry (NMR). In house collaborators are evaluating the blood clotting inhibitor activity of these versatile compounds. The in vitro anti-platelet efficacy will be investigated in platelet-rich plasma, induced by collagen. A detailed structure-activity relationship study is ongoing in hopes of finding the best agent in preventing arterial thrombosis.

Faculty Mentor(s)

Timothy Beng

Department/Program

Biomedical Science

Additional Mentoring Department

Chemistry

Additional Mentoring Department

Funding from Central OUR Grants

Additional Mentoring Department

Funding from Central Faculty-Student Provost Research Grants

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Stereocontrolled Synthesis and Evaluation of Platelet Aggregation Inhibitory Activity of Highly Decorated Lactam Carboxamides

The most common causes of mortality worldwide are currently heart attacks and strokes. They result from significant clotting of blood in the arteries. This is commonly referred to as arterial thrombosis. The search for more selective antithrombotic agents therefore represents an important research objective. One lactam carboxamide (a cyclic amide that bears a noncyclic amide functional group) has recently been found to exhibit remarkable efficacy in reducing arterial thrombosis in mouse models. It outperformed the standard drug, aspirin. In these studies, a diverse library of lactam carboxamides has been assembled in a cost-effective, atom-economical, and orientation-specific manner by utilizing green chemistry. This method used to create the library is modular, chemoselective, and diastereoselective. This provides an excellent opportunity for further therapeutic applications. The structures of the synthesized carboxamides have been confirmed by routine spectroscopic techniques, including nuclear magnetic resonance spectrometry (NMR). In house collaborators are evaluating the blood clotting inhibitor activity of these versatile compounds. The in vitro anti-platelet efficacy will be investigated in platelet-rich plasma, induced by collagen. A detailed structure-activity relationship study is ongoing in hopes of finding the best agent in preventing arterial thrombosis.

https://digitalcommons.cwu.edu/source/2022/COTS/41