A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole sub...A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole substituted compounds as novel analogues of neuraminidase inhibitors in good yields.展开更多
Background It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness （ILl） since 2009, when inhaled zanamivir （RELENZA ） was ...Background It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness （ILl） since 2009, when inhaled zanamivir （RELENZA ） was marketed in China. Methods An uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir （as Rotadisk via Diskhaler device）; 10 mg administered twice daily for 5 days in subjects≥12 years old with ILl. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction real-time reverse transcriptase-polymerase chain reaction （rRT-PCR） test had positive results. Results A total of 400 patients 〉12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects （1%）. Most of the adverse events were mild and did not require any change of treatment. No severe adverse events （SAE） or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates （43 before enrollment, 18 during treatment） proved to be sensitive to zanamivir. Conclusions Zanamivir is well tolerated by Chinese adolescents and adults with ILls. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir. （ChiCTR-TNRC-10000938）展开更多
In this study, we compared Ma Huang Tang (maoto), a traditional Japanese medicine (Kampo), with antiviral drugs to evaluate their respective and combined effect on the duration of fever and other subjective symptoms o...In this study, we compared Ma Huang Tang (maoto), a traditional Japanese medicine (Kampo), with antiviral drugs to evaluate their respective and combined effect on the duration of fever and other subjective symptoms of influenza. Forty-five patients enrolled in this randomized control trial had positive type A influenza on rapid influenza antigen test, provided written consent, and sought treatment at Juntendo University Hospital between November 2008 and March 2009. Using a computer-gen- erated list, patients were randomly assigned to one of the four intervention groups: 1): maoto (TJ-27), 9 subjects;2): Tamiflu (oseltamivir), 13 subjects;3): Relenza (zanamivir), 6 subjects;and 4): maoto/oseltamivir combination, 9 subjects. Six outcome measures were evaluated, including fever, myalgia, headache, arthralgia, fatigue, and cough. Statistical differences were determined by the Bonferroni-adjusted t-test for multiple comparisons. Our results showed that there were no significant differences among the four groups in the time-course profile of fever and the number of days until fever resolution since treatment was initiated. In addition, no significant intergroup differences were detected in the number of days until resolution of myalgia, headache, fatigue, and cough. However, the maoto group reported a more rapid improvement in joint pain than the oseltamivir group (P = 0.01). In conclusion, maoto showed comparable efficacy as antiviral medications in reducing fever and influenza symptoms. As serious concerns over the indiscriminate use, adverse reactions, and resistance to current antiviral drugs continue to grow, maoto may serve as an elegant option for the treatment of influenza.展开更多
基金supported by National Great Project of Scientific and Technical Supporting Programs Funded by Ministry of Science & Technology of China(No.2006BAI01B02)
文摘A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole substituted compounds as novel analogues of neuraminidase inhibitors in good yields.
基金This study was supported by grants from National Natural Science Foundation of China （No. 810 30032/H 19, 81070005/H0104） and Beijing Science and Technology Key Projects Foundation （No. D 101100049810002） and GlaxoSmithkline （China） Investment Co. Ltd.
文摘Background It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness （ILl） since 2009, when inhaled zanamivir （RELENZA ） was marketed in China. Methods An uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir （as Rotadisk via Diskhaler device）; 10 mg administered twice daily for 5 days in subjects≥12 years old with ILl. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction real-time reverse transcriptase-polymerase chain reaction （rRT-PCR） test had positive results. Results A total of 400 patients 〉12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects （1%）. Most of the adverse events were mild and did not require any change of treatment. No severe adverse events （SAE） or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates （43 before enrollment, 18 during treatment） proved to be sensitive to zanamivir. Conclusions Zanamivir is well tolerated by Chinese adolescents and adults with ILls. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir. （ChiCTR-TNRC-10000938）
基金National Key Technology R&D Programof China(Grant 2006BAI01B02)the Key Project for New Drug Re-search from CAS,and the 863 Hi-Tech Program(Grants 2006AA020602,2006AA02Z336)
文摘In this study, we compared Ma Huang Tang (maoto), a traditional Japanese medicine (Kampo), with antiviral drugs to evaluate their respective and combined effect on the duration of fever and other subjective symptoms of influenza. Forty-five patients enrolled in this randomized control trial had positive type A influenza on rapid influenza antigen test, provided written consent, and sought treatment at Juntendo University Hospital between November 2008 and March 2009. Using a computer-gen- erated list, patients were randomly assigned to one of the four intervention groups: 1): maoto (TJ-27), 9 subjects;2): Tamiflu (oseltamivir), 13 subjects;3): Relenza (zanamivir), 6 subjects;and 4): maoto/oseltamivir combination, 9 subjects. Six outcome measures were evaluated, including fever, myalgia, headache, arthralgia, fatigue, and cough. Statistical differences were determined by the Bonferroni-adjusted t-test for multiple comparisons. Our results showed that there were no significant differences among the four groups in the time-course profile of fever and the number of days until fever resolution since treatment was initiated. In addition, no significant intergroup differences were detected in the number of days until resolution of myalgia, headache, fatigue, and cough. However, the maoto group reported a more rapid improvement in joint pain than the oseltamivir group (P = 0.01). In conclusion, maoto showed comparable efficacy as antiviral medications in reducing fever and influenza symptoms. As serious concerns over the indiscriminate use, adverse reactions, and resistance to current antiviral drugs continue to grow, maoto may serve as an elegant option for the treatment of influenza.
