Synthesis of 5-benzyl-2-phenylpyrazolo[1,5-a]pyrazin-4,6(5H,7H)-dione derivatives and discovery of an apoptosis inducer for H322 lung cancer cells

Bioorg Med Chem Lett. 2012 Jan 15;22(2):844-9. doi: 10.1016/j.bmcl.2011.12.049. Epub 2011 Dec 16.

Abstract

A series of substituted 5-benzyl-2-phenylpyrazolo[1,5-a]pyrazin-4,6(5H,7H)-dione derivatives was synthesized by one-step reaction of ethyl 3-phenyl-1H-pyrazole-5-carboxylate derivatives and N-arylalkyl-2-chloroacetamide. Structures of the compounds were determined by IR, (1)H NMR and mass spectroscopy. In addition, a representative single-crystal structure was characterized by using X-ray diffraction analysis. The compound 5j could selectively inhibit the growth of H322 lung cancer cells which contain a mutated p53 gene in a dose-dependent manner through inducing apoptosis of cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry
  • Pyrazines / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-(4-methoxyphenyl)-5-phenethylpyrazolo(1,5-a)pyrazine-4,6(5H,7H)-dione
  • Antineoplastic Agents
  • Pyrazines
  • Pyrazoles