摘要
以不同电性的基团取代顺-3-甲基芬太尼中4-N-丙酰基上的乙基,合成某些顺-3-甲基芬太尼的结构类似物。药理试验结果表明,所合成的化合物均有典型的吗啡样作用。化合物3的镇痛活性略强于顺-3-甲基芬太尼。应用半经验的INDO方法对4个代表化合物进行了量子化学计算,讨论了电子结构与镇痛活性间的关系,化合物3由于氯乙烯基的引入具有与顺-3-甲基芬太尼不同的电子结构特征,氯乙烯基可能作为电子接受体参与了与受体的作用。
The synthesis of some 4-N-propionyl analogs of cis-3-methylfentanyl by acyl chloride method, anhydride method, mixed anhydride method and DCCmethod is reported. The ethyl group in 4-N-propionyl portion of cis-3-methylfentanyl was substituted by some groups with different electronic property. In mouse hotplate test. all compounds showed typical morphine-like action with analgesic potency cor-responding to 49～1963 times that of morphine. Compound 3 was found to exhibit higheranalgesic activity than cis-3-methyl fentanyl. Semiempirical INDO calculationshave been undertaken for 4 typical compounds and it was found that as a result of in-troduction of chlorovinyl, compound 3 exhibited characteristics of electronic structuredifferent from that of cis-3-methyl fentanyl. The relationships between analgesic activityand the electronic structure of these compounds were discussed.
出处
《药学学报》
CAS
CSCD
北大核心
1992年第7期503-509,共7页
Acta Pharmaceutica Sinica
关键词
甲基芬太尼
镇痛活性
芬太尼
Cis--3--methyl fentanyl
Narcotic analgesic activity
Quantum chemical calculation
Structure--activity relationship
