title: Alpha2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior.
abstract: The goal of the present study was to modulate the receptor interaction properties of known alpha 2-adrenoreceptor (AR) antagonists to obtain novel alpha 2-AR agonists with desirable subtype selectivity. Therefore, a phenyl group or one of its bioisosteres or aliphatic moieties with similar steric hindrance were introduced into the aromatic ring of the antagonist lead basic structure. The functional properties of the novel compounds allowed our previous observations to be confirmed. The high efficacy of 7, 12, and 13 as alpha 2-AR agonists and the significant alpha 2C-AR subtype selective activation displayed by 11 and 15 demonstrated that favorable interactions to induce alpha 2-AR activation were formed between the pendant groups of the ligands and the aromatic cluster present in transmembrane domain 6 of the binding site cavity of the receptors.
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: Claudia
authors.initials: C
authors.lastname: Cardinaletti
authors.forename: Cristian
authors.initials: C
authors.lastname: Vesprini
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Ghelfi
authors.forename: Aniket
authors.initials: A
authors.lastname: Farande
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.forename: Jonne M
authors.initials: JM
authors.lastname: Laurila
authors.forename: Anna
authors.initials: A
authors.lastname: Huhtinen
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2