Synthesis of deuterium-enriched and fluorine-substituted plinabulin derivatives and evaluation of their antitumor activities

Mol Divers. 2017 Aug;21(3):577-583. doi: 10.1007/s11030-017-9742-y. Epub 2017 May 9.

Abstract

Deuterium-enriched and fluorine-substituted compounds have been widely applied in drug discovery due to their advantages in the studies of clinical pharmacokinetics and metabolic profiles. Herein we synthesized a library of deuterated and fluorine-substituted plinabulin derivatives, and all 15 D- or F-compounds were characterized by MS, [Formula: see text] NMR and [Formula: see text]. Their antitumor activities were evaluated against human Jurkat T lymphocyte cells.

Keywords: Antitumor activity; Deuterium-enriched; Fluorine-substituted; Parallel synthesis; Plinabulin.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Deuterium / chemistry*
  • Diketopiperazines / chemical synthesis*
  • Diketopiperazines / chemistry
  • Diketopiperazines / pharmacology
  • Fluorine / chemistry*
  • Humans
  • Jurkat Cells
  • Mass Spectrometry
  • Molecular Structure
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Antineoplastic Agents
  • Diketopiperazines
  • NPI 2358
  • Fluorine
  • Deuterium