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; structurally related to the mu-agonist 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane, have been synthesized and tested in binding studies, using H-3-DAMGO as mu-selective ligand. Their different affinity towards mu-opioid receptors has been interpreted on the basis of a molecular modeling study performed through molecular mechanics calculations and high field H-1 MNR spectroscopy. (C) 1997, Elsevier Science Ltd.