2-Phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles, A new class of antimalarial substances†

doi:10.1002/JHET.5570070308

Paper

2-Phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles, A new class of antimalarial substances†

Published Jun 1, 1970 · M. P. Hutt, E. Elslager, L. M. Werbel

Journal of Heterocyclic Chemistry

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33

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0

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Abstract

An investigation of hybrids of 2,5-dimethyl-1,3,4-oxadiazole (I) and α,α,α,α',α',α'-hexachloro-p-xylene (Hetol®) (II) as potential antimalarial agents led to the synthesis of representative 2-phenyI-5-(trichloromethyl)-1,3,4-oxadiazoles (VIa-f, VIII-X) and related trichloromethyl 1,2,4-oxadiazole, 1,3,4-oxadiazoles, and 1,3,4-thiadiazole (VII, XIII-XV). Treatment of the appropriately substituted benzoic: acid hydrazides (IVa-f) with trichloroacetic anhydride afforded the intermediate 1-benzoyl-2-(triehloroacetyl)hydrazines (Va-f) which were cyclized to the desired 5-(chlorophenyl, tolyl, or α,α,α-trifluorotolyl)-2-(trichloromethyl)-1,3,4-oxadiazoles (VIa-f) (44–66%) in situ utilizing phosphorous oxychloride. Chlorination of the 5-tolyl-2-(trichloromethyl)-1,3,4-oxadiazoles (VId-f) afforded 2-(trichloromethyl)-5-(α,α,α-trichloro-m- and p-tolyl)-1,3,4-oxadiazole (VIII and IX) and 2-(α,α,α,α',α',α'-hexachloro-3,5-xylyl)-5-(trichloromethyl)-1,3,4-oxadiazole (X) in 23–56% yield. Each of the 2-phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles (VIa-f, VIII-X) was active against Plasmodium berghei in mice when administered in single 160 or 640 mg./kg. subcutaneous doses or given orally by drug-diet for 6 days at doses of 29–336 mg./kg./day. The 2-(trichloromethyl)-5-(α,α,α-trichlorotolyl)-1,3,4-oxadiazoles (VIII-X) were the most active compounds prepared and exhibited activity against P. berghei comparable with Hetol®. Structure-activity relationships are discussed.

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Study Snapshot

2-phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles show potential as a new class of antimalarial agents with activity comparable to Hetol®.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

2-Phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles, A new class of antimalarial substances†

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References

PAM 1392 (2,4-diamino-6-(3,4-dichlorobenzylamino) quinazoline) as a chemotherapeutic agent: Plasmodium berghei, P. cynomolgi, P.

PAM 1392 is a promising oral drug for treating drug-resistant malaria and other parasitic infections, with potential for use in drug-resistant malaria and protecting mice against acute infections.

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