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Updated: May 27, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones
R Matthew Cross1, Niranjan K Namelikonda, Tina S Mutka
1Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
Abstract:
ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED50=0.05 mg/kg) in rodent malaria models but produced rapid acquisition of parasitological resistance in P. berghei infected mice. Herein we describe the synthesis of analogues of 5 with EC50 as low as 0.15 nM against multidrug resistant P. falciparum. Optimal activity with low cross-resistance indexes (RI) to atovaquone was achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)-4(1H)-quinolone core.
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