Talipexole


Talipexole is a dopamine agonist that is marketed as a treatment for Parkinson's disease in Japan by Boehringer Ingelheim; it was introduced in 1996. As of December 2014 it was not approved for marketing in the US nor in Europe.
Talipexole is a dopamine D2 receptor agonist and interacts with both pre- and post-synaptic receptors. It also is an α2-adrenergic agonist.
The main side effects are drowsiness, dizziness, hallucinations and minor gastrointestinal complaints. In Japan, the Ministry of Health, Labour and Welfare mandated in 2008 that Boehringer add a warning to the label concerning the risk of sudden onset of sleep.

Synthesis

The N-alkylation of azepan-4-one with allyl bromide in the presence of potassium carbonate gives 1-allyl-azepan-4-one. This is halogenated with molecular bromine in acetic acid to give 1-allyl-5-bromohexahydro-4-azepinone. The last step involves cyclization with thiourea in refluxing ethanol, completing the synthesis of talipexole.