Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials.
Basic Information
ID: ALA2169740
Journal: J Med Chem
Title: Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials.
Authors: Zhang Y, Clark JA, Connelly MC, Zhu F, Min J, Guiguemde WA, Pradhan A, Iyer L, Furimsky A, Gow J, Parman T, El Mazouni F, Phillips MA, Kyle DE, Mirsalis J, Guy RK.
Abstract: Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.
CiteXplore: 22435599
DOI: 10.1021/jm201642z
Patent ID: ┄