3-Carboxamido analogues of morphine and naltrexone: synthesis and opioid receptor binding properties

In response to the unexpectedly high affinity for opioid receptors observed in a novel series of cyclazocine analogues where the prototypic 8-OH was replaced by a carboxamido group, we have prepared the corresponding 3-CONH 2 analogues of morphine and naltrexone. High affinity ( K i=34 and 1.7 nM) for μ opioid receptors was seen, however, the new targets were 39- and 11-fold less potent than morphine and naltrexone, respectively. High-affinity binding to μ opioid receptors has been identified in a series of novel 3-carboxamido analogues of morphine and naltrexone.