Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 8, Issue 2, Pages 427-432Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0968-0896(99)00301-6
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The synthesis of paclitaxel esters of malic acid is described. These compounds were found to have improved water solubility and are stable in solution at neutral pH. The C2' modified compounds behave as prodrugs, that is, paclitaxel is generated upon exposure to human plasma, whereas the C7 modified derivatives do not. 2'-Malyl paclitaxel sodium salt demonstrated enhanced antitumour activity and less toxicity in a P388 murine leukaemia in vivo model when compared to paclitaxel. (C) 2000 Elsevier Science Ltd. All rights reserved.
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