Synthesis of hydantoins and thiohydantoins spiro-fused to pyrrolidines: druglike molecules based on the 2-arylethyl amine scaffold

J Comb Chem. 2009 Jul-Aug;11(4):527-38. doi: 10.1021/cc800190z.

Abstract

The synthesis of a 144-compound library of hydantoins and thiohydantoins spiro-fused to pyrrolidines is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in compounds active in the central nervous system. All possible stereoisomers of the two-stereocenter products are synthesized. The 80-membered hydantoin sublibrary was obtained with yields ranging from 58 to 100% (87% average) and purities from 51 to 100% (87% average) and the 64-membered thiohydantoin sublibrary was obtained with yields ranging from 65 to 100% (89% average) and purities from 67 to 100% (93% average).

MeSH terms

  • Amines / chemistry
  • Combinatorial Chemistry Techniques
  • Hydantoins / chemical synthesis*
  • Hydantoins / chemistry
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Stereoisomerism
  • Thiohydantoins / chemical synthesis*
  • Thiohydantoins / chemistry

Substances

  • Amines
  • Hydantoins
  • Pyrrolidines
  • Spiro Compounds
  • Thiohydantoins