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

T J Altstadt; 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

doi:10.1021/jm0102607

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.

Authors

T J Altstadt¹, 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

Affiliation

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.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Ethers
Humans
Magnetic Resonance Spectroscopy
Paclitaxel / analogs & derivatives*
Paclitaxel / chemical synthesis*
Paclitaxel / chemistry
Paclitaxel / pharmacology
Structure-Activity Relationship
Taxoids*
Transplantation, Heterologous
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Ethers
Taxoids
7-methylthiomethylpaclitaxel
Paclitaxel