Cinnamoyl derivatives of 7 alpha-amino- and 7 alpha-(aminomethyl)-N-(cyclopropylmethyl)-6,14-endo-ethanotetrahydronororipavines are high-potency opioid antagonists

Methods have been developed for the synthesis of 7 alpha -amino- and 7 alph a-(aminomethyl)-N-cyclopropylmethyl-6,14-endo-ethanotetrahydronororipavin a nd their cinnamoyl derivatives (Schemes 1 and 3). In displace ment binding assays, the cinnamoyl derivatives 4c and se had high affinity for opioid re ceptors, but no particular selectivity for any receptor type or differences in affinity between 4c and 5c (Table 1). In tissue assays for opioid recep tor function, in which both 4c and 5c were potent antagonists, the aminomet hyl derivative 5c was 20- to 70-fold more potent than the amino derivative 4c (Table 2).These data are in keeping with previously reported in vivo dat a and confirm the major effect of the methylene spacer in 5c.