The discovery of RFI-641 as a potent and selective inhibitor of the respiratory syncytial virus.
The design and synthesis of a new potent and selective inhibitor of the respiratory syncytial virus are described. This compound, RFI-641, emerged from analysis of the structure-activity relationship in a series of biphenyl triazine anionic compounds possessing specific anti-RSV activity. The key synthetic step involves coupling of diaminobiphenyl 11 with two equivalents of chlorotriazine 10 under microwave conditions. RFI-641 inhibited RSV in vitro and in vivo models.
Nikitenko
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Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. nikitea@war.wyeth.com
Raifeld
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Wang
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TZ
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects*; D004195:Disease Models, Animal; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009666:Nose / Q000821:virology; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*; D014226:Triazenes / Q000138:chemical synthesis / Q000494:pharmacology; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology*
D000998:Antiviral Agents; C434804:RFI 641; D013449:Sulfonamides; D014226:Triazenes; D014227:Triazines