Date of Award
Master of Science (MS)
The calcium-sensing receptor (CaSR) is a protein receptor responsible for maintaining the body's calcium and magnesium levels. There is a large unmet medical need for diseases associated with this receptor. CaSR calcimimetics and calcilytics, agonists, and antagonists, respectively, are excellent candidates as therapeutics – a tryptophan derivative is known as L-1,2,3,4-tetrahydronorharman-3-carboxylic acid (TNCA) was first discovered when the crystal structure of the extracellular domain of CaSR was produced. TNCA was found to be a co-agonist of CaSR, calcium, and magnesium. We performed structure-activity (SAR) studies of several nonradioactive fluorine, iodine, and bromine analogs of TNCA obtained via the Pictet-Spingler Cyclization reaction. Several analogs showed promise as agonists and antagonists for CaSR. A fluorine-containing candidate was chosen for radiolabeling with the positron-emitting radioelement [18F]fluorine by aromatic nucleophilic substitution with a boron pinacol ester precursor for preclinical evaluation as a CaSR imaging agent.
Goodman, Matthew, "Synthesis of Novel Tryptophan Drug Candidates for Thera(g)nositcs for the Human Calcium Receptor." Thesis, Georgia State University, 2024.
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