title: Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476.
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.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, P.O. Box 5100, Wallingford, Connecticut 06492-7660, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Altstadt
authors.forename: C R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: J
authors.initials: J
authors.lastname: Golik
authors.forename: K A
authors.initials: KA
authors.lastname: Johnston
authors.forename: J F
authors.initials: JF
authors.lastname: Kadow
authors.forename: F Y
authors.initials: FY
authors.lastname: Lee
authors.forename: B H
authors.initials: BH
authors.lastname: Long
authors.forename: W C
authors.initials: WC
authors.lastname: Rose
authors.forename: D M
authors.initials: DM
authors.lastname: Vyas
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: M J
authors.initials: MJ
authors.lastname: Wu
authors.forename: M D
authors.initials: MD
authors.lastname: Wittman
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004987:Ethers; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D043823:Taxoids; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004987:Ethers; D043823:Taxoids; C426424:7-methylthiomethylpaclitaxel; D017239:Paclitaxel