Herbert Richard H, Gerhard Ute, Mortishire-Smith Russell J, Thomas Steven R, Hollingworth Gregory
The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
Magn Reson Chem. 2005 Aug;43(8):658-61. doi: 10.1002/mrc.1604.
The binding affinities at the human NK-1 receptor of two spirocyclic compounds were found to be similar despite being epimeric at a key stereocentre. This unexpected result prompted a thorough investigation of the solution conformations of the two compounds. This revealed that a conformational switch in the tetrahydrofuran ring enabled the C-3-aryl group to be equatorial in both cases, leading to a similar juxtaposition of the aryl rings.
尽管两种螺环化合物在一个关键立体中心处为差向异构体，但发现它们对人NK-1受体的结合亲和力相似。这一意外结果促使对这两种化合物的溶液构象进行全面研究。结果表明，四氢呋喃环中的构象转换使两种情况下的C-3-芳基均处于平伏键，从而导致芳环的并置方式相似。
