Development of Oseltamivir Phosphonate Congeners as Anti-influenza Agents
نویسندگان
چکیده
منابع مشابه
Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity.
Influenza remains a major health problem for humans and animals.1 At present, four drugs are approved for influenza prophylaxis and treatment:2 amantadine and rimantadine act as the M2 ion channel blockers, whereas Tamiflu (the phosphate salt of oseltamivir ethyl ester) and Relenza (zanamivir) inhibit the activity of neuraminidase (NA). The NA inhibitors (NAIs) are designed to have (oxa)cyclohe...
متن کاملA practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity.
Two phosphonate compounds 1a (4-amino-1-phosphono-DANA) and 1b (phosphono-zanamivir) are synthesized and shown more potent than zanamivir against the neuraminidases of avian and human influenza viruses, including the oseltamivir-resistant strains. For the first time, the practical synthesis of these phosphonate compounds is realized by conversion of sialic acid to peracetylated phosphono-DANA d...
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Influenza virus neuraminidase (NA) catalyses the cleavage of sialic acid residues terminally linked to glycoproteins and glycolipids and plays an important role in the replication of the virus. Recently, several potent NA inhibitors have been synthesized based on the rational design of mimicking the transition state of the sialic acid cleavage. Zanamivir and oseltamivir (GS 4104, the prodrug of...
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The urgent need of neuraminidase inhibitors (NI) has provided an impetus for understanding the structure requisite at molecular level. Our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. The main objective of present study is to develop selective NI, with least toxicity and dru...
متن کاملOseltamivir, an anti-influenza virus drug, produces hypothermia in mice.
Oseltamivir phosphate (Tamiflu), an anti-influenza virus drug, is hydrolyzed by carboxylesterase to an active metabolite. The metabolite inhibits the influenza virus-specific neuraminidase. In this study, the effects of oseltamivir on normal core body temperature were studied in mice. Oseltamivir (30-300 mg/kg, intraperitoneally (i.p.) and 100-1000 mg/kg, orally (p.o.)) dose-dependently lowered...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2012
ISSN: 0022-2623,1520-4804
DOI: 10.1021/jm3008486