Synthesis of spiro-1,2-dioxolanes and their activity against Plasmodium falciparum
| Autor: | Jon Clardy, Armando P. Ramirez, Joseph F. Cortese, Derek C. Martyn, K. A. Woerpel, Margaret A. Rush, Meaghan J. Beattie, Vishal Patel |
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| Rok vydání: | 2008 |
| Předmět: |
Annulation
medicine.drug_class Stereochemistry Carboxylic acid Chemistry Pharmaceutical Clinical Biochemistry Amino Acid Motifs Plasmodium falciparum Antiprotozoal Agents Pharmaceutical Science Carboxamide Antigens Protozoan Heme Biochemistry Chemical synthesis chemistry.chemical_compound Antimalarials parasitic diseases Drug Discovery medicine Animals Humans Amines Molecular Biology chemistry.chemical_classification biology Alkene Organic Chemistry Biological activity Dioxolanes biology.organism_classification Malaria Peroxides chemistry Models Chemical Dioxolane Drug Design Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 18(24) |
| ISSN: | 1464-3405 |
| Popis: | Artemisinin-derived compounds play an integral role in current malaria chemotherapy. Given the virtual certainty of emerging resistance, we have investigated spiro-1,2-dioxolanes as an alternative scaffold. The endoperoxide functionality was generated by the SnCl 4 -mediated annulation of a bis -silylperoxide and an alkene. The first set of eight analogs gave EC 50 values of 50–150 nM against Plasmodium falciparum 3D7 and Dd2 strains, except for the carboxylic acid analog. A second series, synthesized by coupling a spiro-1,2-dioxolane carboxylic acid to four separate amines, afforded the most potent compound (EC 50 ∼5 nM). |
| Databáze: | OpenAIRE |
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