Thurkauf A, de Costa B, Mattson M V, France C P, Price M T, Olney J W, Woods J H, Jacobson A E, Rice K C
Laboratory of Medicinal Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Med Chem. 1990 Aug;33(8):2211-5. doi: 10.1021/jm00170a027.
A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.
通过1-(1-氰基环己基)-1,2,3,6-四氢吡啶(1)与适当取代的格氏试剂反应制备了一系列1-[1-芳基环己基]-1,2,3,6-四氢吡啶。测试了所得化合物对苯环利定结合位点的亲和力。然后对选定的化合物进行测试，以评估它们在猴子中产生氯胺酮样反应的能力和/或在幼鼠缺氧/缺血模型中显示神经保护作用的能力。虽然发现结合位点亲和力与辨别性刺激效应密切相关，但发现在该系列中它是神经保护功效的一个较差指标。
