title: Novel human neuropeptide Y Y5 receptor antagonists for the treatment of obesity. Synthesis and biological evaluation of pyridine hydrazide derivatives.
abstract: A series of new pyridine hydrazide derivatives with high and selective antagonist activity at the human neuropeptide Y Y5 receptor were developed. Introduction of electron-withdrawing groups into the arylsulfonamide rest, together with the 3-pyridyl analogue in the hydrazide moiety, led to a significant improvement of potency and solubility, affording trans-N-(4-[N'-(pyridine-3-carbonyl)hydrazino-carbonyl]cyclohexylmethyl)-2,4-dichloro-benzenesulfonamide (14), which binds to the hY5 receptor with an IC50 value of 7.44 nmol/L.
authors.affiliation: Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galiano
authors.forename: Oihana
authors.initials: O
authors.lastname: Erviti
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez
authors.forename: Antonio
authors.initials: A
authors.lastname: Moreno
authors.forename: Laura
authors.initials: L
authors.lastname: Juanenea
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000627:therapeutic use*; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D007202:Indicators and Reagents; D009765:Obesity / Q000188:drug therapy*; D011725:Pyridines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis
chemical_list: D019440:Anti-Obesity Agents; D006834:Hydrazines; D007202:Indicators and Reagents; D011725:Pyridines; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C100568:neuropeptide Y5 receptor