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).
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.
Antonio
A
Moreno
Silvia
S
Pérez
Silvia
S
Galiano
Laura
L
Juanenea
Oihana
O
Erviti
Carmen
C
Frígola
Ignacio
I
Aldana
Antonio
A
Monge
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