Liu Huaqing, Kerdesky Francis A, Black Lawrence A, Fitzgerald Michael, Henry Rodger, Esbenshade Timothy A, Hancock Arthur A, Bennani Youssef L
Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6123, USA.
J Org Chem. 2004 Jan 9;69(1):192-4. doi: 10.1021/jo035264t.
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.
GT - 2331是一种已进入临床试验阶段的强效组胺H(3)拮抗剂。本文描述了该化合物及其对映体的高效多克级合成方法。文献报道GT - 2331是4 - [2 - (5,5 - 二甲基己 - 1 - 炔基)环丙基] - 1H - 咪唑的右旋(+)、活性更强的对映体，其绝对构型为(1R,2R)-1。然而，我们发现4 - [2 - (5,5 - 二甲基己 - 1 - 炔基)环丙基] - 1H - 咪唑的右旋、活性更强的对映体的绝对构型为(1S,2S)。我们建议重新考虑GT - 2331的绝对构型。
