Synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives as human neuropeptide Y Y5 receptor antagonists for the treatment of obesity.
NPY is the most potent orexigenic peptide identified up to now. Stimulation of food intake is measured by the Y(1) and Y(5) receptor subtypes. In this study, the synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives are described as potential selective antagonists of the human NPY Y(5) receptor. The SAR of these series was examined and the amide derivatives were the compounds that showed the best activities. trans-N-(4-[(Quinolin-3-yl)aminocarbonyl]cyclohexylmethyl)-2,4-dichlorobenzenesulfonamide (42) bound to the human neuropeptide Y Y(5) receptor with a 2 nM IC(50).
Moreno
Antonio
A
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.
Pérez
Silvia
S
Galiano
Silvia
S
Juanenea
Laura
L
Erviti
Oihana
O
Frígola
Carmen
C
Aldana
Ignacio
I
Monge
Antonio
A
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D019440:Anti-Obesity Agents; D003510:Cyclohexanes; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C097212:neuropeptide Y-Y1 receptor; C100568:neuropeptide Y5 receptor