The synthesis and structure-activity relationship of pyridazinones as glucan synthase inhibitors

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1819-22. doi: 10.1016/j.bmcl.2011.01.058. Epub 2011 Jan 21.

Abstract

A structure-activity relationship study of the lead 5-[4-(benzylsulfonyl)piperazin-1-yl]-4-morpholino-2-phenyl-pyridazin-3(2H)-one 1 has resulted in the identification of 2-(3,5-difluorophenyl)-4-(3-fluorocyclopentyloxy)-5-[4-(isopropylsulfonyl)piperazin-1-yl]-pyridazin-3(2H)-one 11c as a β-1,3-glucan synthase inhibitor. Compound 11c exhibited significant efficacy in an in vivo mouse model of Candida glabrata infection.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glucosyltransferases / antagonists & inhibitors*
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry*
  • Pyridazines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyridazines
  • Glucosyltransferases
  • glucan synthase