Finney Z G, Riley T N
J Med Chem. 1980 Aug;23(8):895-9. doi: 10.1021/jm00182a016.
A study of ring-expanded analogues of the 4-(propananilido)piperidine analgesics has been undertaken in order to evaluate the influence of this structural modification on both analgesic activity and physical-dependence capacity. Thus, a series of 1-substituted 4-(propananilido)perhydroazepine derivatives was synthesized and pharmacologically evaluated in mice for analgesic activity and physical-dependence capacity. The results of this study indicate that the ring-expanded analogues of the 4-(propananilido)piperidines retain a relatively high degree of analgesic potency, except in the case of the 1-phenylethylated analogue which is approximately 150-fold less potent than the correspondingly 1-substituted piperidine analgesic. Evaluation of physical-dependence capacity of the most potent 1-substituted 4-(propananilido)perhydroazepines reveals no significant difference for these compounds as compared with morphine. The 4-(propananilido)perhydroazepines having 1-substitutents in common with known opiate antagonists failed to exhibit antagonism of morphine analgesia.
为了评估这种结构修饰对镇痛活性和身体依赖性能力的影响，已对4-（丙酰苯胺基）哌啶镇痛药的环扩展类似物进行了一项研究。因此，合成了一系列1-取代的4-（丙酰苯胺基）全氢氮杂卓衍生物，并在小鼠中对其镇痛活性和身体依赖性能力进行了药理学评估。这项研究的结果表明，4-（丙酰苯胺基）哌啶的环扩展类似物保留了相对较高程度的镇痛效力，但1-苯乙基化类似物的情况除外，其效力比相应的1-取代哌啶镇痛药低约150倍。对最有效的1-取代4-（丙酰苯胺基）全氢氮杂卓的身体依赖性能力评估显示，与吗啡相比，这些化合物没有显著差异。具有与已知阿片拮抗剂相同的1-取代基的4-（丙酰苯胺基）全氢氮杂卓未能表现出对吗啡镇痛的拮抗作用。
