This study represents a good example od lead pharmacokinetic optimization. Combined application of analytical techniques, SAR analysis, chemical synthesis and binding studies enabled the identification of compound UCM924 (N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide) as an alternative to the hypno-inducing lead compound UCM765, an MT2 melatonin receptor partial agonist, which exhibits a very short half-life in the presence of rat oxidative enzymes. The new analogue UCM924 displayed a binding profile similar to that of the parent UCM765 on cloned human melatonin receptors and a significantly longer half-life in the presence of rat liver S9 fraction.
N-(Anilinoethyl)amides: design and synthesis of metabolically stable, selective melatonin receptor ligands.
SPADONI, GILBERTO;BEDINI, ANNALIDA;LUCARINI, SIMONE;TARZIA, GIORGIO
2009
Abstract
This study represents a good example od lead pharmacokinetic optimization. Combined application of analytical techniques, SAR analysis, chemical synthesis and binding studies enabled the identification of compound UCM924 (N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide) as an alternative to the hypno-inducing lead compound UCM765, an MT2 melatonin receptor partial agonist, which exhibits a very short half-life in the presence of rat oxidative enzymes. The new analogue UCM924 displayed a binding profile similar to that of the parent UCM765 on cloned human melatonin receptors and a significantly longer half-life in the presence of rat liver S9 fraction.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
