title: Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for mu opioid and I2-imidazoline receptors: synthesis and pharmacological screening.
abstract: Derivatives of N-(1-phenethyl-4-piperidyl)propanamides incorporating guanidinium and 2-aminoimidazolinium groups have been prepared by a synthetic approach involving first introduction of a spacer between the piperidine and the functional group by reductive amination of piperidinone. The formation of each of these functional groups was carried out using N-N'-di(tert-butoxycarbonyl)thiourea and 2-methylthioimidazolinium iodide, respectively. These structures have been designed to incorporate two pharmacologic goals into one entity. Radioligand binding assays have been used to study their affinity for opioid (mu, delta and kappa) and I2-imidazoline receptors. Two of them, 10 and 16, showed high affinity for mu opioid receptors and functionally they had moderate analgesic properties in the hot plate and writhing tests. The in vitro studies on guinea pig ileum (GPI) indicated that both compounds are mu opioid agonists. In what concerns I2-imidazoline receptor activity, these derivatives showed low affinity around 6 to 7 times less than idazoxan.
authors.affiliation: Instituto de Química Médica, CSIC, Juan de la Cierva, 3, E-28006, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Montero
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.forename: Nadine
authors.initials: N
authors.lastname: Jagerovic
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.forename: Rocío
authors.initials: R
authors.lastname: Girón
authors.forename: Carlos
authors.initials: C
authors.lastname: Goicoechea
authors.forename: Ma Isabel
authors.initials: MI
authors.lastname: Martín
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D004353:Drug Evaluation, Preclinical; D019791:Guanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D010880:Piperidines / Q000737:chemistry; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D012677:Sensation / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000700:Analgesics; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D010880:Piperidines; D011955:Receptors, Drug; D017450:Receptors, Opioid, mu; C032727:piperidine; D019791:Guanidine