Design and Synthesis of Endoperoxide Antimalarial Prodrug Models

• Published in: Angewandte Chemie International Edition Vol. 43; no. 32; pp. 4193 - 4197
• Main Authors: O'Neill, Paul M., Stocks, Paul A., Pugh, Matthew D., Araujo, Nuna C., Korshin, Edward E., Bickley, Jamie F., Ward, Stephen A., Bray, Patrick G., Pasini, Erica, Davies, Jill, Verissimo, Edite, Bachi, Mario D.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 13.08.2004; WILEY‐VCH Verlag; Wiley
• Subjects: antimalarial agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - chemistry; chalcones; Chalcones - chemistry; Chemistry; Chemistry, Multidisciplinary; combination chemotherapy; cysteine protease inhibitors; Cysteine Proteinase Inhibitors - chemistry; Drug Design; endoperoxides; Peroxides - chemical synthesis; Peroxides - chemistry; Physical Sciences; Prodrugs - chemical synthesis; Prodrugs - chemistry; Science & Technology; chalcones; antimalarial agents; MECHANISM; ANALOGS; combination chemotherapy; ARTEMISININ DERIVATIVES; RO-42-1611 ARTEFLENE; YINGZHAOSU; HEMOGLOBIN DEGRADATION; CYSTEINE PROTEINASE; cysteine protease inhibitors; endoperocides; PLASMODIUM-FALCIPARUM; QINGHAOSU ARTEMISININ; MALARIA PARASITE
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200453859

A masked combination chemotherapy which relies on the embedding of a number of active components, in a latent form, within a single endoperoxidic chemical entity is the aim of the research presented. The approach is illustrated by means of purposely designed bicyclic endoperoxide prodrug prototypes 1 and subsequently validated through the study of model compounds 2 (Ar=Ph, p‐FC6H4, p‐ClC6H4).