Novel Dopamine D2 Receptor Antagonists and Methods of Their Use

Investigators at the NIH have identified a series of novel, small molecule antagonists of the dopamine D2 receptor. Among the dopamine receptor (DAR) subtypes, D2 DAR is arguably one of the most validated drug targets in neurology and psychiatry. For instance, all receptor-based anti-Parkinsonian drugs work via stimulating the D2 DAR, whereas all FDA approved antipsychotic agents are antagonists of this receptor. Unfortunately, most agents that act as antagonists of D2 DAR are problematic, either they are less efficacious than desired or cause multiple adverse effects. Thus, it is desirable to develop a class of novel therapeutic agents with high selectivity for the D2 DAR. This invention describes dihydrobenzo[b,f][1,4]thiazepine-8-carboxamide compounds, methods of making these compounds, methods of characterizing their in vitro activity, demonstration of in vivo activity in animals, as well as methods of using these compounds to treat central nervous system (CNS) related disorders.