Orally Active, Water-Soluble Antimalarial 3-Aryltrioxanes: Short Synthesis and Preclinical Efficacy Testing in Rodents
| Autor: | Suji Xie, Ik-Hyeon Paik, Theresa A. Shapiro, Kristina Borstnik, Heung Bae Jeon, Gary H. Posner, Poonsakdi Ploypradith |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Trioxane
Plasmodium berghei Carboxylic acid medicine.medical_treatment Administration Oral Cyclohexanone Benzoates Chemical synthesis Antimalarials Mice Structure-Activity Relationship chemistry.chemical_compound Oral administration In vivo Drug Discovery medicine Animals Benzoxepins Organic chemistry Artemisinin chemistry.chemical_classification Stereoisomerism Malaria Solubility chemistry Molecular Medicine Artelinic acid medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 45:3824-3828 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm020210h |
| Popis: | Short chemical syntheses of four new antimalarial trioxanes are presented, starting with inexpensive and commercially available cyclohexanone. Almost exclusive formation of the trioxane 12alpha-stereoisomers simplifies product purification. Carboxyphenyltrioxanes 3 and 5 are thermally stable in air even at 60 degrees C for 24 h. When administered orally, these new carboxyphenyltrioxanes are highly efficacious in curing malaria-infected mice. Important for their practical in vivo administration, these new synthetic antimalarial trioxanes 3 and 5 are 14-20 times more soluble in water at pH 7.4 than is artelinic acid (1), a leading semisynthetic, herb-derived antimalarial trioxane drug candidate. |
| Databáze: | OpenAIRE |
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