Fentanyl derivatives bearing aliphatic alkaneguanidinium moieties:: a new series of hybrid molecules with significant binding affinity for μ-opioid receptors and I2-imidazoline binding sites

A new series of fentanyl derivatives [i.e., N-[1-(2-phenethyl)-4-piperidyl]-N-(guanidinoalkyl)propanamide] bearing aliphatic alkaneguanidinium moieties were prepared. Their affinities for the V opioid receptors and for the I-2-imidazoline binding sites (I-2-IBS) were determined on human post-mortem prefrontal cortex membranes. All of these hybrid compounds had significant and/or very high affinity for both receptors in the nanomolar range, meaning an improvement compared to the prototype N-[1-(2-phenethyl)-4-piperidyl]-N-(guanidinopropyl)propanamide previously reported. (C) 2003 Elsevier Ltd. All rights reserved.