Affiliation:
1. Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 123 Bevier Road, Piscataway, NJ 08854, USA
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.
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