Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors

Bioorg Med Chem. 2011 Jun 15;19(12):3709-16. doi: 10.1016/j.bmc.2011.02.017. Epub 2011 Feb 13.

Abstract

Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o,- m- and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m- and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Bromine / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Histone Demethylases / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Stereoisomerism
  • Tranylcypromine / chemical synthesis*
  • Tranylcypromine / chemistry
  • Tranylcypromine / pharmacology*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Tranylcypromine
  • Histone Demethylases
  • Bromine