Novel human neuropeptide Y Y5 receptor antagonists for the treatment of obesity. Synthesis and biological evaluation of pyridine hydrazide derivatives.
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.
Galiano
Silvia
S
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, Pamplona, Spain.
Erviti
Oihana
O
Pérez
Silvia
S
Moreno
Antonio
A
Juanenea
Laura
L
Aldana
Ignacio
I
Monge
Antonio
A
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
D019440:Anti-Obesity Agents; D006834:Hydrazines; D007202:Indicators and Reagents; D011725:Pyridines; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C100568:neuropeptide Y5 receptor