Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en.
A series of ester prodrugs of 7-O-methyl derivative of Zanamivir (compound 3) was synthesized and their efficacy was evaluated in an influenza infected mice model by intranasal administration. Compound 7c (CS-8958), octanoyl ester prodrug of the C-9 alcohol of compound 3, was found to be much longer-acting than Zanamivir. Furthermore, the in vivo efficacies of compounds 12a, 12b, and 12c, the linear alkyl ester prodrug of the carboxylic acid, were comparable to that exerted by compound 7c.
Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co, Ltd, Tokyo, Japan. honda.takeshi.sx@daiichisankyo.co.jp
Takeshi
T
Honda
Shuku
S
Kubo
Takeshi
T
Masuda
Masami
M
Arai
Yoshiyuki
Y
Kobayashi
Makoto
M
Yamashita
D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004952:Esters; D029521:Alphainfluenzavirus / Q000187:drug effects* / Q000201:enzymology; D029524:Betainfluenzavirus / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053243:Zanamivir / Q000494:pharmacology
D000998:Antiviral Agents; D004952:Esters; D011355:Prodrugs; D009439:Neuraminidase; D053243:Zanamivir