RESUMEN
Obovatol derivatives were synthesized and evaluated for anti-platelet activity. Three derivatives (1, 2, 4i) displayed equipotent activity to obovatol in arachidonic acid-induced platelet aggregation. An initial SAR study revealed that the introduction of alkoxy group in B ring could enhance inhibitory activity.
Asunto(s)
Compuestos de Bifenilo/farmacología , Éteres Fenílicos/farmacología , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Alcoholes/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Araquidónico/antagonistas & inhibidores , Ácido Araquidónico/farmacología , Compuestos de Bifenilo/química , Colágeno/farmacología , Relación Dosis-Respuesta a Droga , Éteres Fenílicos/química , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Conejos , Relación Estructura-ActividadRESUMEN
Concise total synthesis of obovatol (1) was achieved from the commercially available eugenol (5) via linear 4 steps in 40% overall yield. The key features of the synthesis involve the chemoselective orthobromination of phenol in the presence of isolated double bond and the efficient Cu-catalyzed Ullmann coupling of two aromatic moieties for the diaryl ether skeleton.
Asunto(s)
Antiinfecciosos/síntesis química , Compuestos de Bifenilo/síntesis química , Bromo/química , Cobre/química , Fenoles/química , Éteres Fenílicos/síntesis química , Alquenos/química , Catálisis , Éteres , Ligandos , Espectrofotometría Infrarroja , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Stereocontrolled methods for the direct and divergent synthesis of the silylenol ethers possessing amino group from beta-amino aldehydes have been achieved. These enol ethers with the defined olefin geometry could be key building blocks for the synthesis of the medicinally impor tant compounds.
Asunto(s)
Aldehídos/química , Éteres/síntesis química , Alquenos/química , Alquilación , Compuestos de Bencilo/síntesis química , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Metilación , Silanos/síntesis química , EstereoisomerismoRESUMEN
A series of novel diaryl ethers possessing various functional groups were synthesized and evaluated for antiproliferative activity in human myeloid leukemia HL-60 cells. Among the compounds examined, compounds 10, 17, 20, 24, and 33 showed moderate to potent antiproliferative activity. These derivatives were further examined in terms of their abilities to inhibit tubulin polymerization; however, all of the tested compounds were relatively ineffective. The reference compound E7010 with an IC(50) of 0.34 microM exhibited potent antiproliferative activity and significantly inhibited tubulin polymerization in a dose-dependent manner.