Probing Structural Requirements of Positive Allosteric Modulators of the M4 Muscarinic Receptor

This thesis examines the synthesis, characterisation and pharmacological testing of a diverse range of compounds as potential positive allosteric modulators of the M4 muscarinic receptor. A number of compounds have been identified to produce promising pharmacological profiles. The M4 receptor has been implicated in cognitive disorders such as schizophrenia and Alzheimer’s disease, where pharmaceutical treatments with fewer side effects are highly sought after. The allosteric approach to targeting the M4 receptor, allows for selectivity of the M4 receptor subtype over the other muscarinic receptor subtypes and provides the potential for the treatment of symptoms associated with these debilitating cognitive disorders.