Large-scale synthesis of GMP grade alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate

Arzneimittelforschung. 2007;57(3):155-63. doi: 10.1055/s-0031-1296599.

Abstract

The leflunomide (CAS 75706-12-6) metabolite (LFM) analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13, DDE-28, CAS 244240-24-2), is a rationally designed inhibitor of the anti-apoptotic enzyme Bruton's tyrosine kinase (BTK). LFM-A13 is being developed as a novel dual-function anticancer drug with apoptosis-promoting and anti-thrombotic properties. LFM-A13 was prepared under current Good Manufacturing Practice (cGMP) conditions on the scale of kilograms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemical synthesis*
  • Antineoplastic Agents / chemical synthesis*
  • Chromatography, Gas
  • Chromatography, High Pressure Liquid
  • Crystallization
  • Drug Compounding / standards
  • Drug Contamination
  • Drug Industry / standards
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Metals, Heavy / analysis
  • Nitriles / chemical synthesis*
  • Particle Size
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Water / analysis

Substances

  • Amides
  • Antineoplastic Agents
  • Indicators and Reagents
  • LFM A13
  • Metals, Heavy
  • Nitriles
  • Water