Related Experiment Video
Updated: Jun 6, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives
Hiroaki Shiraki1, Michael P Kozar, Victor Melendez
1Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, United States.
Abstract:
In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.
Related Concept Videos
Anthelminthic Agents
Antiprotozoal Agents
Physical Properties of Amines
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Antifungal Agents
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

