Synthesis and biological evaluation of C-3'-modified analogs of 9(R)-dihydrotaxol

J Med Chem. 1994 Aug 19;37(17):2655-63. doi: 10.1021/jm00043a005.

Abstract

Taxol (1) is considered a most exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihydrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family. Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino group might be optimal. However, relatively little is known about the effects of the 3'-phenyl ring on activity. The synthesis and biological evaluation of analogs of 3 modified at the C-3' position are described. This study revealed that the 3'-phenyl ring was not required for activity and identified several compounds which had equal or greater in vitro and in vivo activity than taxol.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Cell Division / drug effects
  • Drug Design
  • Indicators and Reagents
  • Lung Neoplasms / drug therapy
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Structure
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis*
  • Paclitaxel / chemistry
  • Paclitaxel / toxicity
  • Spectrometry, Mass, Fast Atom Bombardment
  • Stereoisomerism
  • Structure-Activity Relationship
  • Taxoids*

Substances

  • Antineoplastic Agents
  • Indicators and Reagents
  • Taxoids
  • 9-dihydrotaxol
  • Paclitaxel