Insecticidal lead identification by screening benzopyrano[4,3-c] pyrazol-3(2H)-ones library constructed from multiple-parallel synthesis under microwave irradiation

Bioorg Med Chem. 2006 Dec 15;14(24):8666-74. doi: 10.1016/j.bmc.2006.08.020. Epub 2006 Sep 1.

Abstract

A rapid library-generation via liquid-phase multiple-parallel synthesis of 2-(substituted)benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones, bearing two points of diversity, under microwave irradiation was successfully performed using chromenone-3-carboxylic acids as starting materials. Compared to an identical library generated by conventional parallel synthesis, microwave-assisted parallel synthesis dramatically decreased reaction times from an average of 16h to 13min, and the yields of products and intermediates were improved in most cases. A bioassay indicated that the compounds of the library exhibited excellent insecticidal activity against T. cinnabarinus at the dosage of 250mgL(-1), and some compounds still exhibited insecticidal activity when the dosage was reduced to 50mgL(-1). This shows that 2-(substituted) benzyl-1-benzopyrano[4,3-c]pyrazol-3(2H)-ones might be used as lead structures for further optimization. To our knowledge, this is the first report about the application of solution-phase multiple-parallel synthesis under microwave irradiation to construct libraries of benzopyrano-[4,3-c]pyrazol-3(2H)-ones with insecticidal activity. The coupling of microwave technology with liquid-phase parallel synthesis constitutes a novel and particularly attractive avenue for the rapid generation of structurally diverse libraries for lead discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Combinatorial Chemistry Techniques*
  • Insecticides / chemical synthesis
  • Insecticides / chemistry
  • Insecticides / isolation & purification
  • Insecticides / pharmacology
  • Microwaves*
  • Molecular Structure
  • Peptide Library*
  • Pyrazoles / chemistry
  • Pyrazoles / isolation & purification
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship
  • Tetranychidae / drug effects*

Substances

  • Insecticides
  • Peptide Library
  • Pyrazoles
  • pyrazole