2,2,6- and 2,3,5-trimethylpiperazines as monocyclic analogues of the mu-opioid agonist 3,8-diazabicyclo[3.2.1]octanes: Synthesis, modeling, and activity

A series of trimethylpiperazine derivatives, struturally related to the μ-agonist 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane have been synthesized and rested in binding studies, using 3H-DAMGO as μ-selective ligand. Their different affinity towards μ-opioid receptors has been interpreted on the basis of a molecular modeling study performed through molecular mechanics calculations and high field 1H MNR spectroscopy.