The discovery of BMS-275183: an orally efficacious novel taxane

Bioorg Med Chem. 2003 Oct 1;11(20):4315-23. doi: 10.1016/s0968-0896(03)00495-4.

Abstract

The evolution of 2, a C-4-methylcarbonate analogue of paclitaxel with minimal oral bioavailability and oral efficacy, into its C-3'-t-butyl-3'-N-t-butyloxycarbonyl analogue (15i), a novel taxane with oral efficacy in preclinical models that is comparable to iv administered paclitaxel, is described.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Biological Availability
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacokinetics*
  • Bridged-Ring Compounds / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Evaluation, Preclinical
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Rats
  • Structure-Activity Relationship
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics*
  • Taxoids / pharmacology

Substances

  • Antineoplastic Agents
  • BMS-275183
  • Bridged-Ring Compounds
  • Taxoids
  • taxane