Synthesis and Characterization of D1 Dopamine Receptor Positive Allosteric Modulators

Many pharmacologic agents used to treat CNS disorders, such as schizophrenia, Parkinson’s disease and Alzheimer’s disease, target the dopaminergic system. Recent evidence suggests an important role for the D1 dopamine receptor (D1R), with signaling enhancement being shown to improve cognitive function. While the clinical adoption of traditional D1R orthosteric agonists has been stymied by acute tolerance and adverse effects, D1R positive allosteric modulators (PAMs) present an innovative approach to amplify D1R signaling without the clinical pitfalls of other D1R agonists. This project aims to synthesize thiophene-based D1R PAMs targeting a novel D1R allosteric site, to screen for receptor selectivity, and to optimize potentiation.Doctor of Pharmac