An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration

J Org Chem. 2004 Jan 9;69(1):192-4. doi: 10.1021/jo035264t.

Abstract

GT-2331 is a potent histamine H(3) antagonist which has entered clinical trials. Efficient multigram syntheses of this compound and its enantiomer are described. The literature reports that GT-2331 is the dextrorotatory (+), more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory, more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole has the (1S,2S) absolute configuration. We suggest a reconsideration of the absolute configuration of GT-2331.

MeSH terms

  • Crystallography, X-Ray
  • Histamine Agents / chemical synthesis*
  • Histamine Agents / chemistry
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Models, Molecular
  • Molecular Structure
  • Receptors, Histamine H3 / drug effects*

Substances

  • 4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole
  • Histamine Agents
  • Imidazoles
  • Receptors, Histamine H3