MCR synthesis of a tetracyclic tetrazole scaffold

Bioorg Med Chem. 2015 Jun 1;23(11):2699-715. doi: 10.1016/j.bmc.2014.12.021. Epub 2014 Dec 20.


Scaffold diversity is key in the ongoing exercise of discovery of novel bioactive compounds using high throughput screening (HTS). Based on the Ugi tetrazole synthesis we have designed novel bi- and tri-cyclic scaffolds featuring interesting pharmacophore properties. The compounds of the scaffold (B) are synthesizable in large diversity and numbers in two steps using (hetero)phenylethylamines, HN3, oxo components and iscyanoacetaldehyde(dimethylacetale). The chemistry is amenable to parallel synthesis and is used to enhance and fill the screening decks of the European Lead factory (ELF). Here, we are reporting full experimental details, scope and limitations of the reaction, cheminformatic analysis and the 3D structures of selected compounds.

Keywords: Isocyanide; Parallel; Pictet–Spengler; Synthesis; Tetrazol; Ugi.

Publication types

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

MeSH terms

  • Drug Discovery*
  • Models, Molecular
  • Molecular Structure
  • Polycyclic Compounds / chemical synthesis*
  • Tetrazoles / chemical synthesis*


  • Polycyclic Compounds
  • Tetrazoles