STUDIES ON IRREVERSIBLE BINDING OPIOID RECEPTOR AGONISTS AND ANTAGONISTS Ⅰ. SYNTHESIS OF 7α-AMINO-6, 14-ENDOETHENO-TETRAHYDROORIPAVINE DERIVATIVES

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.