【摘要】 本文设计和合成了10个结构刚性、具反应活性基团的7α-氨基-6,14-乙烯撑基-四氢奥利文衍生物和它们的N-烯丙基类似物。药理筛选结果:N-甲基类衍生物大都有较强的镇痛活性,其中(11 a)不仅镇痛活性和安全比分别达吗啡的6和13倍,而且结合力强成瘾性小;(14)是有效的不可逆结合的激动剂,而(12 a),(12 b)和(13)都有不可逆结合的拮抗作用,它们的拮抗强度均相当干纳洛酮。更多还原

【Abstract】 Ten derivatives of 7 a-amino 6, 14-endoetheno-tetrahydrooripavine, possessing chemoaffinity functional group in order to achieve irreversible attachment to the opiate-receptor complex, were designed and synthesized for the investigation of opioid receptor. Preliminary pharmacological results showed that most of the Nmethyl compounds possess potent analgesic activity in vivo and in vitro. The analgesic potency and LD₅₀/ED₅₀ ratio of 7α-diphenyl ester phosphamide （11 a） were 6 and 13 times as great as morphine respectively in mice by hot plate test. All monomethyl ester fumaramide compounds （12 a, 12 b, 13 and 14） exhibited apparent ability of irreversible binding in the MVD assay.更多还原