RESUMEN
Several potent and efficacious MCHr1 antagonists containing an ortho-amino benzamide or nicotinamide chemotype have been identified, exemplified by 28 and 50.
Asunto(s)
Niacinamida/análogos & derivados , Receptores de Somatostatina/antagonistas & inhibidores , ortoaminobenzoatos/síntesis química , Animales , Benzamidas/síntesis química , Benzamidas/farmacocinética , Benzamidas/farmacología , Concentración 50 Inhibidora , Ratones , Ratones Endogámicos , Niacinamida/farmacocinética , Niacinamida/farmacología , Farmacocinética , Receptores de Somatostatina/agonistas , Relación Estructura-Actividad , Distribución Tisular , ortoaminobenzoatos/farmacocinética , ortoaminobenzoatos/farmacologíaRESUMEN
An efficient and highly enantioselective (>/=92% ee) catalytic method for conjugate addition of alkylzinc reagents to cyclic nitroalkenes is reported. Reactions are promoted in the presence of 0.5-5 mol % (CuOTf)2.C6H6 and 1-10 mol % of chiral amino acid-based phosphine ligands at 0 degrees C in toluene. The Cu-catalyzed reactions can be effectively carried out with small-, medium-, and large-ring nitroalkenes. Depending on the reaction conditions used, either the nitro or the corresponding alpha-substituted ketone product can be readily accessed by the present protocol.
Asunto(s)
Alquenos/química , Cobre/química , Hidrocarburos Cíclicos/síntesis química , Cetonas/síntesis química , Nitrocompuestos/química , Compuestos Organometálicos/química , Catálisis , Ciclohexanos/química , Ciclohexenos , Hidrocarburos Cíclicos/químicaRESUMEN
Highest enantioselectivities so far with dialkylzinc reagents! Quaternary carbon centers are formed enantioselectively through a Cu-catalyzed allylic substitution reaction that is promoted by pyridinyl peptide-based ligands in the presence of dialkylzinc reagents. The modularity of this new class of chiral ligands is exploited for reactivity and selectivity optimization.