Click chemistry based solid phase supported synthesis of dopaminergic phenylacetylenes

Bioorg Med Chem. 2007 Dec 1;15(23):7248-57. doi: 10.1016/j.bmc.2007.08.038. Epub 2007 Aug 25.

Abstract

'Click resins' enable solid phase supported reactions to work under nearly perfect conditions fulfilling the requirements of click chemistry. Utilizing the formylpyrrolylmethyltriazole (FPMT) linker 6, which is readily available via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), a BAL strategy could be successfully applied for a parallel synthesis of dopaminergic phenylacetylens. A focused library of 20 test compounds revealing three points of diversity was generated by a four-step SPOS approach including microwave assisted Sonogashira coupling. GPCR-ligand binding assays indicated excellent dopamine D3 and D4 receptor binding affinities which were identified to cause a partial agonist activity for the most potent test compounds 2c,e,i,k.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylene / analogs & derivatives*
  • Acetylene / chemical synthesis*
  • Acetylene / pharmacology
  • Alkynes / chemistry
  • Animals
  • Azides / chemistry
  • Binding Sites
  • Binding, Competitive / drug effects
  • CHO Cells
  • Catalysis
  • Cell Line
  • Combinatorial Chemistry Techniques / methods*
  • Copper / chemistry
  • Cricetinae
  • Cricetulus
  • Cyclization
  • Humans
  • Ligands
  • Molecular Structure
  • Receptors, Biogenic Amine / drug effects
  • Resins, Synthetic / chemistry*
  • Small Molecule Libraries
  • Stereoisomerism
  • Structure-Activity Relationship
  • Swine

Substances

  • Alkynes
  • Azides
  • Ligands
  • Receptors, Biogenic Amine
  • Resins, Synthetic
  • Small Molecule Libraries
  • Copper
  • Acetylene