POLYMER-BOUND PACLITAXEL DERIVATIVES

摘要

A polymer conjugate consisting essentially of: from 90 to 99.9 mol % of units represented by formula (a); from 0.1 to 5 mol % of units represented by formula (b), wherein one of R1 and R2 is a copolymer residue of formula (c), and the other one is hydrogen atom; from 0 to 9.9 mol % of units represented by formula (d), wherein R is a phenyl or t-butoxy group, R3 is H or an acetyl group, A and A1 which may be the same or different, represent a chemical single bond, an amino acid residue or peptide spacer selected from (beta) Ala, Gly, Phe-Gly, Phe-Phe-, Leu-Gly, Val-Ala, Phe-Ala, Leu-Phe, Leu-Ala, Phe-Leu-Gly, Phe-Phe-Leu, Leu-Leu-Gly, Phe-Tyr-Ala, Phe-Gly-Phe, Phe-Phe-Gly, Phe-Leu-Gly-Phe, Gly-Phe-Leu-Gly-Phe, Gly-(beta)Ala, Phe-Gly-(beta)Ala, Phe-Phe-(beta)Ala, Leu-Gly-(beta)Ala, Val-Ala-(beta)Ala, Phe-Ala-(beta)Ala, Leu-Phe-(beta)Ala, Leu-Gly-(beta)Ala, Phe-Leu-Gly-(beta)Ala, Phe-Phe-Leu (beta)Ala, Leu-Leu-Gly-(beta)Ala, Phe-Tyr-Ala-(beta)Ala, Phe-Gly-Phe-(beta), Phe-Phe-Gly(beta)Ala, Phe-Leu-Gly-Phe-(beta)Ala or Gly-Phe-Leu-Gly-Phe-(beta)Ala. The compounds are endowed with antitumor activity and show improved water solubility and decreased toxicity in comparison with paclitaxel or its known analogs. A method for their preparation and pharmaceutical compositions containing them are also described.