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. 2009 Oct 21;7(20):4163-5.
doi: 10.1039/b911483a. Epub 2009 Aug 7.

Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine

Peter Wipf  1 , Tingting Mo, Steven J Geib, Diana Caridha, Geoffrey S Dow, Lucia Gerena, Norma Roncal, Erin E Milner
Affiliations

Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine

Peter Wipf et al. Org Biomol Chem. .

Abstract

Two novel SF5 analogs of the antimalarial agent mefloquine were synthesized in 5 steps and 10-23% overall yields and found to have improved activity and selectivity against malaria parasites. This work also represents the first report of SF5-substituted quinolines.

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Figures

Fig. 1
Fig. 1
Mefloquine (1).
Fig. 2
Fig. 2
Electron-density surfaces/electrostatic potential maps calculated with Spartan 08 (HF/6–31G*) for 2 analogs of 1, 4-methyl-8-penta-fluorosulfanyl-2-trifluoromethylquinoline (left) and 4-methyl-2,8-bis-(trifluoromethyl)quinoline (right).
Fig. 3
Fig. 3
Stereoview of the X-ray structure of 3.
Fig. 4
Fig. 4
Structures of trifluoromethylated quinoline methanols 10 and 11 used as references in the biological assays.
Scheme 1
Scheme 1
Synthesis of mefloquine analogs 2 and 3.
See this image and copyright information in PMC

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