HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity.

Abstract
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 diethyl ester (5) as a key intermediate in three steps by a novel approach. In comparison with zanamivir, the high affinity of 1a and 1b can be partly attributable to the strong electrostatic interactions of their phosphonate groups with the three arginine residues (Arg118, Arg292, and Arg371) in the active site of neuraminidases. These phosphonates are nontoxic to the human 293T cells; they protect cells from influenza virus infection with EC(50) values in low-nanomolar range, including the wild-type WSN (H1N1), the 2009 pandemic (H1N1), the oseltamivir-resistant H274Y (H1N1), RG14 (H5N1), and Udorn (H3N2) influenza strains.
AuthorsJiun-Jie Shie, Jim-Min Fang, Po-Ting Lai, Wen-Hsien Wen, Shi-Yun Wang, Yih-Shyun E Cheng, Keng-Chang Tsai, An-Suei Yang, Chi-Huey Wong
JournalJournal of the American Chemical Society (J Am Chem Soc) Vol. 133 Issue 44 Pg. 17959-65 (Nov 09 2011) ISSN: 1520-5126 [Electronic] United States
PMID21942552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Organophosphonates
  • Neuraminidase
  • Zanamivir
Topics
  • Antiviral Agents (chemical synthesis, chemistry, pharmacology)
  • Catalytic Domain (drug effects)
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Neuraminidase (antagonists & inhibitors, metabolism)
  • Organophosphonates (chemical synthesis, chemistry, pharmacology)
  • Orthomyxoviridae (drug effects, enzymology)
  • Stereoisomerism
  • Structure-Activity Relationship
  • Zanamivir (chemical synthesis, chemistry, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: