Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1775-9. doi: 10.1016/j.bmcl.2006.01.030. Epub 2006 Jan 24.

Abstract

The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s<10nM. Ancillary hERG activity was evaluated for this series of inhibitors.

MeSH terms

  • Cell Line, Tumor
  • Female
  • Humans
  • Kinesins / antagonists & inhibitors*
  • Models, Molecular
  • Ovarian Neoplasms / pathology
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacology*
  • Spindle Apparatus / chemistry

Substances

  • Pyrroles
  • Kinesins