Synthesis and anti-influenza activities of carboxyl alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir).
Three alkoxyalkyl 2-carboxylate ester derivatives related to zanamivir were synthesized. All of the analogs of zanamivir modified at carboxylic moiety with alkoxyalkyl esters 1a-c showed higher activities than ribavirin on influenza A and B virus in the MDCK cells. Oral treatment or intraperitoneal administration of compound 1c showed significantly protective effects in mice infected with influenza A virus with low toxicities.
Liu
Zong-Ying
ZY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Wang
Bo
B
Zhao
Li-Xun
LX
Li
Yu-Huan
YH
Shao
Hua-Yi
HY
Yi
Hong
H
You
Xue-Fu
XF
Li
Zhuo-Rong
ZR
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D015195:Drug Design; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D007252:Influenza Vaccines / Q000737:chemistry; D007251:Influenza, Human / Q000188:drug therapy*; D007263:Infusions, Parenteral; D020128:Inhibitory Concentration 50; D051379:Mice; D012254:Ribavirin / Q000494:pharmacology; D053243:Zanamivir / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007252:Influenza Vaccines; D012254:Ribavirin; D053243:Zanamivir