title: alpha 2-adrenoreceptors profile modulation. 2. Biphenyline analogues as tools for selective activation of the alpha 2C-subtype.
abstract: A series of derivatives structurally related to biphenyline (3) was designed with the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results obtained demonstrated that the presence of a correctly oriented function with positive electronic effect (+sigma) in portion X of the ligands is an important factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and 19). Homology modeling and docking studies support experimental data and highlight the crucial role for the hydrogen bond between the pyridine nitrogen in position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in the alpha(2C)-subtype, only.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gentili
authors.forename: Francesca
authors.initials: F
authors.lastname: Ghelfi
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.forename: Cristian
authors.initials: C
authors.lastname: Vesprini
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Crassous
authors.forename: Hervé
authors.initials: H
authors.lastname: Paris
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrieri
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000595:Amino Acid Sequence; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C547774:ADRA2C protein, human; D058647:Adrenergic alpha-2 Receptor Agonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D013844:Thiazoles