Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir
| Autor: | Pei-Shan Lee, Jim-Min Fang, Kung-Cheng Liu, Shi-Yun Wang, Yih-Shyun E. Cheng, Chi-Huey Wong |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.drug_class
Stereochemistry Clinical Biochemistry Drug Evaluation Preclinical Administration Oral Neuraminidase Pharmaceutical Science Naphthols Antiviral Agents Biochemistry Cell Line Hydrolysis chemistry.chemical_compound Oseltamivir Zanamivir Influenza Human Drug Discovery medicine Humans Moiety Prodrugs Carboxylate Enzyme Inhibitors Molecular Biology Guanidine Ions Molecular Structure Neuraminidase inhibitor Organic Chemistry virus diseases Esters Carbon Dioxide Prodrug chemistry Influenza A virus Intramolecular force Lipophilicity Molecular Medicine Hydrophobic and Hydrophilic Interactions medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 19:4796-4802 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2011.06.080 |
| Popis: | Zanamivir (ZA) is a potent anti-influenza drug, but it cannot be administrated orally because of the hydrophilic carboxylate and guanidinium groups. Guanidino-oseltamivir (GO) is another effective neuraminidase inhibitor with polar guanidinium group under physiological conditions. The ester prodrugs ZA-HNAP (5) and GO-HNAP (6) were prepared to incorporate a 1-hydroxy-2-naphthoic (HNAP) moiety to attain good lipophilicity in the intramolecular ion-pairing forms. ZA-HNAP resumed high anti-influenza activity (EC(50)=48 nM), in cell-based anti-influenza assays, by releasing zanamivir along with nontoxic HNAP. Under similar conditions, the hydrolysis of the GO-HNAP ester was too sluggish to show the desired anti-influenza activity. |
| Databáze: | OpenAIRE |
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