Bivalent opioid peptide analogues with reduced distances between pharmacophores

To investigate the role of distance between two opioid peptide pharmacophores on in vitro and in vivo activities, three new bivalent opioid analogues have been synthesized in which the dipeptide Tyr-D-Phe was connected with diamine moieties ("bridges"). The analogue with a hydrazine bridge has high receptor affinity to mu, kappa, and delta receptor types, as well as potent and long acting antinociceptive activity after intraperitoneal administration.