Minick Douglas J, Copley Royston C B, Szewczyk Jerzy R, Rutkowske Randy D, Miller Luke A
GlaxoSmithKline, Discovery Research, Research Triangle Park, NC 27709, USA.
Chirality. 2007 Sep;19(9):731-40. doi: 10.1002/chir.20431.
GT-2331 [(+)-1] is one of the most potent members of a class of chiral drug substances used to regulate the synthesis and release of histamine by the histamine H3 receptor, and as such, is an important biomarker for pharmaceutical companies conducting research in this field. In addition to overall structural features, the bioactivity of this molecule has also been found to be highly dependent on absolute stereochemistry, making the reliable assignment of this property a necessity. X-ray diffraction studies have provided conflicting data, leaving its three-dimensional structure uncertain. In view of this, its absolute configuration was investigated by vibrational circular dichroism. Results from this study provided independent assignment of this important molecule as the (1S,2S)-enantiomer.
GT - 2331 [（+）-1]是一类用于通过组胺H3受体调节组胺合成与释放的手性药物中活性最强的成员之一，因此，对于在该领域开展研究的制药公司而言，它是一种重要的生物标志物。除了整体结构特征外，还发现该分子的生物活性高度依赖于绝对立体化学，因此可靠地确定这一性质很有必要。X射线衍射研究给出了相互矛盾的数据，其三维结构仍不确定。鉴于此，通过振动圆二色性对其绝对构型进行了研究。该研究结果独立确定了这种重要分子为（1S，2S）-对映体。
