Fentanyl derivatives bearing aliphatic alkaneguanidinium moieties: a new series of hybrid molecules with significant binding affinity for mu-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 micro 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.
Dardonville
Christophe
C
Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006, Madrid, Spain. dardonville@iqm.csic.es
Jagerovic
Nadine
N
Callado
Luis F
LF
Meana
J Javier
JJ
D000473:Alkanes / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D005283:Fentanyl / Q000737:chemistry / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D054755:Imidazoline Receptors; D051379:Mice; D010879:Piperazines / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011955:Receptors, Drug / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
C442383:3-(4-guanidinophenyl)-N-(2-phenylethyl)-3-((4-(3,3-diphenylpropylaminocarbonyl)piperazin-1-yl)carbonyl)propanamide; D000473:Alkanes; D006146:Guanidines; D054755:Imidazoline Receptors; D010879:Piperazines; D011955:Receptors, Drug; D017450:Receptors, Opioid, mu; D005283:Fentanyl