Astemizole analogues with reduced hERG inhibition as potent antimalarial compounds

Publication date: Available online 7 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Junjun Tian, Leen Vandermosten, Steve Peigneur, Lien Moreels, Jef Rozenski, Jan Tytgat, Piet Herdewijn, Philippe E. Van den Steen, Steven De Jonghe
Astemizole is a H1-antagonist endowed with antimalarial activity, but has hERG liabilities. Systematic structural modifications of astemizole led to the discovery of analogues that display very potent activity as inhibitors of the growth of the Plasmodium parasite, but show a decreased hERG inhibition, when compared to astemizole. These compounds can be used as starting point for the development of a new class of antimalarials.

Graphical abstract

http://ift.tt/2y7UofJ