Lednicer D, VonVoigtlander P F, Emmert D E
J Med Chem. 1981 Apr;24(4):404-8. doi: 10.1021/jm00136a010.
The effect on potency of modification of the carbonyl function of analgesics derived from 4-(dimethylamino)-4-arylcyclohexan-1-one was studied by reduction and by addition of nucleophiles. The resulting amino alcohols were separated and assigned structures on the basis of X-ray crystallography, NMR, and TLC mobility. The trans (OH and N) isomers were invariably more potent than the cis. Inclusion of flat lipophilic moieties (phenyl, cyclohexenyl) at a distance of at least two carbon atoms from the carbon bearing hydroxyl led to increases in potency by orders of magnitude. The possible significance of this on receptor interaction is discussed.
通过还原和添加亲核试剂，研究了对源自4-(二甲基氨基)-4-芳基环己烷-1-酮的镇痛药羰基官能团进行修饰对药效的影响。分离得到了生成的氨基醇，并根据X射线晶体学、核磁共振和薄层色谱迁移率确定了其结构。反式（OH和N）异构体的药效始终比顺式异构体更强。在距带有羟基的碳原子至少两个碳原子的距离处引入扁平亲脂性基团（苯基、环己烯基）会使药效提高几个数量级。讨论了这一点对受体相互作用可能具有的意义。
