Solution-phase parallel annulation of (thio)hydantoins to tetrahydroisoquinolines and tetrahydro-beta-carbolines containing the 2-arylethyl amine scaffold

J Comb Chem. 2009 Jul-Aug;11(4):547-55. doi: 10.1021/cc8001926.

Abstract

The one-step solution-phase parallel synthesis of two structurally diverse libraries of pharmacologically important compounds is described. The presented compounds combine three privileged structures: the 2-arylethyl amine moiety, a tetrahydro(hetero)areno[c]pyridine, and a (thio)hydantoin. These compounds are synthesized by annulation of a hydantoin or a 2-thiohydantoin ring to tri- or tetracyclic scaffolds, containing the 2-arylethyl amine moiety and a tetrahydroisoquinoline, a tetrahydro-beta-carboline, or a tetrahydrofuro[3,2-c]pyridine. The annulation leads to pharmacologically relevant structural motifs such as imidazopyrroloisoquinolines, dioxoloimidazopyrroloisoquinolines, furoimidazopyrrolopyridines, and imidazopyrrolopyridoindoles. Both libraries were obtained with quantitative yields. The 36-membered hydantoin library was obtained with purities from 57 to 100% (90% average) and the 32-membered thiohydantoin library with purities from 73 to 100% (94% average).

MeSH terms

  • Amines / chemistry
  • Carbolines / chemical synthesis*
  • Carbolines / chemistry
  • Combinatorial Chemistry Techniques / methods*
  • Pharmaceutical Preparations / chemical synthesis
  • Pharmaceutical Preparations / chemistry
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / chemistry
  • Thiohydantoins / chemical synthesis*
  • Thiohydantoins / chemistry

Substances

  • Amines
  • Carbolines
  • Pharmaceutical Preparations
  • Tetrahydroisoquinolines
  • Thiohydantoins
  • tryptoline