Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists

Dopamine (D2) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D2 partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D2 partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model.