Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476

  • J Med Chem. 2001 Dec 20;44(26):4577-83. doi: 10.1021/jm0102607.
T J Altstadt  1 ,  C R Fairchild ,  J Golik ,  K A Johnston ,  J F Kadow ,  F Y Lee ,  B H Long ,  W C Rose ,  D M Vyas ,  H Wong ,  M J Wu ,  M D Wittman
Affiliations
  • 1. Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, P.O. Box 5100, Wallingford, Connecticut 06492-7660, USA.
PMID: 11741476 DOI: 10.1021/jm0102607
Abstract

The preparation of C-7 paclitaxel ethers is described. Various substituted ethers were prepared via activation of the corresponding methylthiomethyl ether followed by alcohol addition. Variation of the C-7 ether group as well the 3' side chain position led to the discovery of a novel taxane, BMS-184476 (4), with preclinical antitumor activity superior to paclitaxel.