A novel approach of water-soluble paclitaxel prodrug with no auxiliary and no byproduct: design and synthesis of isotaxel.
A novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform of paclitaxel, has no additional functional auxiliaries released during conversion to paclitaxel, which would be a great advantage in toxicology and medical economics.
Hayashi
Yoshio
Y
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-Ku, Kyoto 607-8412 Japan.
Skwarczynski
Mariusz
M
Hamada
Yoshio
Y
Sohma
Youhei
Y
Kimura
Tooru
T
Kiso
Yoshiaki
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D014867:Water
D000970:Antineoplastic Agents; D011355:Prodrugs; C477186:isotaxel; D014867:Water; D017239:Paclitaxel