Synthesis of Trypanosoma cruzi Lanosterol 14alpha Demethylase (TcCYP51) Inhibitors for the Treatment of Chagas Disease.

摘要

Chagas is labeled as a neglected tropical disease (NTD) and has had no successful new drugs in the past 30 years. The current available drugs for treatment of Chagas disease, benznidazole and nifurtimox, have proven to be largely ineffective for chronic stages of the disease, and have significant side effects. With over 9 million people infected with Chagas disease, there is a substantial need for new drugs. Recent studies into new therapies have led to the identification of a new target of inhibition, Trypanosoma cruzi cytochrome P450 sterol C14 alpha demethylase (TcCYP51). Inhibition of this has been achieved and a potent scaffold for further optimization was identified. This thesis discusses the further development of this scaffold for improved inhibition and bioavailability. Of the compounds made, none were seen to have an improved efficacy in vitro but do provide further structure activity relationship information.