Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine

J Med Chem. 2009 Nov 26;52(22):6958-61. doi: 10.1021/jm901181h.

Abstract

The design, synthesis, and biological characterization of an orally active prodrug (3) of gemcitabine are described. Additionally, the identification of a novel co-crystal solid form of the compound is presented. Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa. The compound has entered clinical trials and is being evaluated as a potential new anticancer agent.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Colonic Neoplasms / drug therapy
  • Crystallization
  • Crystallography, X-Ray
  • Cytidine / chemistry
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / chemistry
  • Deoxycytidine / pharmacology
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Prodrugs / administration & dosage
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry*
  • Prodrugs / pharmacology*
  • Solubility

Substances

  • Antineoplastic Agents
  • Prodrugs
  • Deoxycytidine
  • Cytidine
  • gemcitabine