Date of Award

2005

Degree Type

Honors Paper

First Advisor

Gary P. Lutz, Ph.D.

Abstract

It has been shown that 1-oleoyl lysophosphatid ic acid (LPA; 1-acyl-2-glycerol-3-phosphate) plays a vital role in the progression and proliferation of ovarian cancer. The design and synthesis of LPA receptor selective agonists and antagonists has been the focus of intense research within the last ten years .1 During the Research Experience for Undergraduate s (REU) internship at the University of Virginia 4-bromo-2-(hydroxymethyl)pyridine (intermediate 43) was designed and synthesized based on earlier results. Intermediate 43 was used to modify a current LPA analogue. Modification of current LPA analogues may result in the discovery of potent and metabolically stable LPA antagonists specific to a particular LPA receptor. Several additional structures of new potential antagonists will be proposed , which may eventually allow for the elucidation of LPA receptor mediated signaling and physiological responses. Identification of lead compound s and the biological processes of ovarian cancer associated with LPA and its individual receptors will ultimately assist in the development of therapeutic candidates.

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