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Antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives. | LitMetric

Antimalarial activities of new guanidylimidazole and guanidylimidazoline derivatives.

J Med Chem

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910, United States.

Published: October 2011

AI Article Synopsis

Article Abstract

A series of new guanidylimidazole derivatives was prepared and evaluated in mice and Rhesus monkeys infected with malarial sporozoites. The majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of Plasmodium falciparum. Compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of P. berghei at 160 and 320 mg/kg/day × 3 po. Compounds 8a showed better causal prophylactic activity than primaquine, tafenoquine, and Malarone in the Rhesus test. In the radical curative test, 8a cured one monkey and delayed relapse of another for 74 days at 30 mg/kg/day × 7 by im. By oral dosing, 8a delayed relapse 81 days for one and 32 days for other vs 11-12 days for control monkeys treated with 10 mg/kg of chloroquine by po alone. Compound 8h, which showed superior activity to 8a in mouse test, delayed the relapse of treated monkeys for 21-26 days at 30 mg/kg/day × 7 by oral.

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Source
http://dx.doi.org/10.1021/jm200503sDOI Listing

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