8-carboxamidocyclazocine analogues: Redefining the structure-activity relationships of 2,6-methano-3-benzazocines

Unexpectedly high affinity for opioid receptors has been observed for a nov el series of cyclazocine analogues where the prototypic 8-OH was replaced b y a carboxamido group. For mu and kappa opioid receptors, the primary carbo xamido derivative of cyclazocine ((+/-)-15) displayed high affinity (K-i=0. 41 and 0.53 nM, respectively) nearly comparable to cyclazocine. A high enan tiopreference ((2R,6R,11R)-) for binding was also observed. Compound (+/-)- 15 also displayed potent antinociception activity in mice when administered icv. (C) 2001 Elsevier Science Ltd. All rights reserved.