Parallel Synthesis of bis-heterocyclic isoxazolylmethyl- and isoxazolinylmethylpyrazoles

J Comb Chem. 2010 Jan-Feb;12(1):129-36. doi: 10.1021/cc900133k.

Abstract

The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH(2)-pyrazoles is described. X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with >or=90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Combinatorial Chemistry Techniques / methods*
  • Crystallography, X-Ray
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Pharmaceutical Preparations / chemical synthesis*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Stereoisomerism

Substances

  • Heterocyclic Compounds
  • Oxadiazoles
  • Pharmaceutical Preparations
  • Pyrazoles