Waters J A
J Med Chem. 1977 Nov;20(11):1496-9. doi: 10.1021/jm00221a027.
Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol were synthesized and evaluated for analgesic activity. 1-Methyl-4-piperidinol 4-piperonylate (14) exhibited activity in the codeine range (mouse hot plate). In monkeys, 14 acted neither as a typical narcotic agonist nor as a typical antagonist and it showed no physical dependence liability of the morphine type. The nonquaternary C-4 peperidinol esters 1a, 4, 8, and 14 exhibited marginal to virtually no binding to the opiate receptor in rat brain homogenates. The interaction of various functional groups of this series with potential binding sites of a nonopiate type receptor is discussed.
合成了1-甲基-4-哌啶醇的杂环和胡椒酸酯，并对其镇痛活性进行了评估。1-甲基-4-哌啶醇胡椒酸酯（14）在可待因范围内表现出活性（小鼠热板法）。在猴子身上，14既不是典型的麻醉激动剂，也不是典型的拮抗剂，且未表现出吗啡类的身体依赖性。非季铵化的C-4哌啶醇酯1a、4、8和14在大鼠脑匀浆中与阿片受体的结合很微弱甚至几乎没有结合。讨论了该系列各种官能团与非阿片类受体潜在结合位点的相互作用。
