title: Guanidine and 2-aminoimidazoline aromatic derivatives as alpha2-adrenoceptor ligands: searching for structure-activity relationships.
abstract: In this paper, we report the synthesis of three new 2-aminoimidazoline (compounds 4b, 5b, and 6b) and three new guanidine derivatives (compounds 7b, 8b, and 9b) as potential alpha(2)-adrenoceptor antagonists for the treatment of depression. Their pharmacological profile was evaluated in vitro in human brain tissue and compared to the potential antidepressant 1 and the agonists 2 and 3. All new substrates were evaluated by in vitro functional [(35)S]GTPgammaS binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Compound 8b was found to be an antagonist in vitro and was subjected to in vivo microdialysis experiments in rats. Moreover, a new synthesis of the precursor amines for compounds 4b-9b is presented.
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Isabel
authors.initials: I
authors.lastname: Rozas
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Ortega
authors.forename: Amaia M
authors.initials: AM
authors.lastname: Erdozain
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000068438:Brimonidine Tartrate; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D006146:Guanidines; D007093:Imidazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000068438:Brimonidine Tartrate