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.
Huaqing Liu  1 ,  Francis A Kerdesky ,  Lawrence A Black ,  Michael Fitzgerald ,  Rodger Henry ,  Timothy A Esbenshade ,  Arthur A Hancock ,  Youssef L Bennani
Affiliations
  • 1. Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6123, USA. [email protected]
PMID: 14703397 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.

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