An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration.
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.
Liu
Huaqing
H
Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6123, USA. huaqing.liu@abbott.com
Kerdesky
Francis A
FA
Black
Lawrence A
LA
Fitzgerald
Michael
M
Henry
Rodger
R
Esbenshade
Timothy A
TA
Hancock
Arthur A
AA
Bennani
Youssef L
YL
D018360:Crystallography, X-Ray; D018494:Histamine Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D018100:Receptors, Histamine H3 / Q000187:drug effects*
C114969:4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole; D018494:Histamine Agents; D007093:Imidazoles; D018100:Receptors, Histamine H3