Incorporation of an Isohexide Subunit into the Endochin-like Quinolone Scaffold

Abstract

In order to improve the drug-likeness qualities, the antimalarial endochin-like quinolone (ELQ) scaffold has been modified by replacing the 4-(trifluoromethoxy)phenyl portion with an isoidide unit that is further adjustable by varying the distal O-substituents. As expected, the water solubilities of the new analogs are greatly improved, and the melting points are lower. However, the antimalarial potency of the new analogs is reduced to EC50 > 1 millimolar, a result ascribable to the hydrophilic nature of the new substitution.

Keywords

• malaria
• isoidide
• Suzuki coupling
• endochin like quinolones
• Mitsunobu reaction
• cyt bc1 complex