Novel tryptophan dioxygenase inhibitors and combined tryptophan dioxygenase/5-HT reuptake inhibitors

Tryptophan dioxygenase (TDO) is a liver enzyme that is responsible for the majority of the metabolism of tryptophan. A series of novel 3-(2-pyridylethenyl)indoles are shown to be potent inhibitors of TDO with selected members of the series also having 5-hydroxy tryptamine (5-HT) reuptake inhibitory activity. These compounds are shown to provide significant increases in the levels of tryptophan and 5-HT in the cerebrospinal fluid and are thus of interest for antidepressant therapy.