Weng J H, Xu X R, Zhu Y C, Zhou J, Xu H, Chi Z Q
Shanghai Institute of Materia Medica, Academia Sinica.
Yao Xue Xue Bao. 1990;25(3):178-85.
Ohmefentanyl is not only a potent analgesic agent, but also a selective ligand for mu opioid receptor. In order to search for more potent analgesics, more selective ligands and long duration of analgesic action in 3-methylfentanyl derivatives, we made modifications of the 1-phenethyl and 4-N-propionyl groups in 3-methylfentanyl and synthesized 15 new compounds. The analgesic activity, duration of analgesic action, receptor binding affinity and opioid sub-receptor selectivity of some of these compounds were measured. Primary pharmacological results showed that most of the compounds in this series possessed morphine-like effects. The analgesic activities of them were about 2-180 times more potent than that of morphine. The duration of analgesic action of the tested compounds was 6-10 times longer than that of fentanyl. The receptor binding affinities (IC50) of compounds 1-4 were 10(-7)-10(-8) mol. Compound 13 displayed the best binding selectivity on mu opioid receptor site with ratio mu/delta greater than 700 in rat brain membrane and mu/delta = 1000 in mouse brain membrane. The new compound may be proposed as a useful tool in studying the opioid receptor. According to the result of equations in reference 11, compounds 7-14 were designed and prepared. The observed log 1/c values of them were much closer to the calculated values.
奥米芬太尼不仅是一种强效镇痛药，也是μ阿片受体的选择性配体。为了在3-甲基芬太尼衍生物中寻找更强效的镇痛药、更具选择性的配体和更长的镇痛作用持续时间，我们对3-甲基芬太尼的1-苯乙基和4-N-丙酰基进行了修饰，合成了15种新化合物。测定了其中一些化合物的镇痛活性、镇痛作用持续时间、受体结合亲和力和阿片受体亚型选择性。初步药理结果表明，该系列中的大多数化合物具有类吗啡作用。它们的镇痛活性比吗啡强约2-180倍。受试化合物的镇痛作用持续时间比芬太尼长6-10倍。化合物1-4的受体结合亲和力（IC50）为10（-7）-10（-8）mol。化合物13在大鼠脑膜中对μ阿片受体位点表现出最佳的结合选择性，μ/δ比值大于700，在小鼠脑膜中μ/δ = 1000。该新化合物可被提议作为研究阿片受体的有用工具。根据参考文献11中的方程式结果，设计并制备了化合物7-14。它们观察到的log 1/c值与计算值更接近。
