Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: pyridazines

Bioorg Med Chem. 2012 May 1;20(9):2803-10. doi: 10.1016/j.bmc.2012.03.035. Epub 2012 Mar 24.

Abstract

Special tetrasubstituted pyridazines are potent fungicides by promoting the tubulin polymerisation, hereby disrupting the microtubule dynamics in the fungus. They are monocyclic analogs of similar substituted triazolopyrimidines and pyridopyrazines with the same mode of action. The fungicidal activity of these pyridazines was evaluated against the plant pathogens Botrytis cinerea (grey mould), Mycosphaerella graminicola (wheat leaf blotch) and Alternaria solani (potato and tomato early blight). Structure-activity relationship studies revealed the importance of a methyl and a chlorine substituent next to both ring nitrogen atoms and two aryl or heteroaryl groups in the other two pyridazine positions.

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Ascomycota / drug effects*
  • Botrytis / drug effects*
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry*
  • Pyridazines / pharmacology*
  • Structure-Activity Relationship
  • Swine
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology

Substances

  • Antifungal Agents
  • Pyridazines
  • Tubulin Modulators