DeGraw J I, Lawson J A, Crase J L, Johnson H L, Ellis M, Uyeno E T, Loew G H, Berkowitz D S
J Med Chem. 1978 May;21(5):415-22. doi: 10.1021/jm00203a002.
A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.
合成了一系列 N-仲烷基和 N-叔烷基去甲吗啡，并对其镇痛效力、拮抗活性和阿片受体结合进行了评估。利用计算机辅助构象分析图谱来协助选择用于合成的化合物，并将受体事件与体内观察结果进行关联。N-叔烷基去甲吗啡 5a-c 没有激动剂活性；然而，一些仲烷基类似物表现出有趣的混合激动剂-拮抗剂作用。N-仲丁基和 N-(α-甲基烯丙基)去甲吗啡被拆分为 R 和 S 异构体，它们表现出定量药理学差异。N-仲丁基 S 异构体 10a 显示出与吗啡相近的镇痛作用以及类似烯丙吗啡的拮抗活性。初步测试表明该化合物仅有轻微的身体依赖性证据。
