Takeda M, Inoue H, Noguchi K, Honma Y, Kawamori M
J Med Chem. 1977 Feb;20(2):221-8. doi: 10.1021/jm00212a007.
A series of 53 1-phenyl-6-azabicyclo[3.2.1]octanes (1) has been tested for their analgetic and narcotic antagonist activities. Structure-activity relationships were investigated by varying the structural parameters. The most interesting compound in this series, the 1-(3-hydroxphenyl)-6,7-dimethyl derivative 8, shows the profile of a well-balanced antagonist-analgesic agent with a very mild physical dependence capacity. The absolute stereochemistry of its active enantiomer [(+)8] was established by the x-ray study and the chemical transformation to the phenylmorphan [(+)-II]. (+)-8 was stereochemically correlated also with the active enantiomer of the 7-demethyl derivatives [(+)-7] by chemical transformation and CD measurement. Certain structural and stereochemical correlations between these compounds (7 and 8) and other known antagonist-analgetics are discussed.
对一系列53种1-苯基-6-氮杂双环[3.2.1]辛烷（1）进行了镇痛和麻醉拮抗活性测试。通过改变结构参数研究了构效关系。该系列中最有趣的化合物，即1-（3-羟基苯基）-6,7-二甲基衍生物8，显示出一种平衡良好的拮抗剂-镇痛药的特征，具有非常轻微的身体依赖性。通过X射线研究以及将其化学转化为苯基吗啡[（+）-II]确定了其活性对映体[（+）8]的绝对立体化学。通过化学转化和圆二色性测量，（+）-8在立体化学上也与7-去甲基衍生物[（+）-7]的活性对映体相关。讨论了这些化合物（7和8）与其他已知拮抗剂-镇痛药之间的某些结构和立体化学相关性。
