RESUMO
A series of phenylacylsulfonamides has been prepared as antagonists of Bcl-2/Bcl-xL. In addition to potent binding affinities for both Bcl-2 and Bcl-xL, these compounds were shown to induce classical markers of apoptosis in isolated mitochondria. Overall weak cellular potency was improved by the incorporation of polar functionality resulting in compounds with moderate antiproliferative activity.
Assuntos
Antineoplásicos/síntese química , Mitocôndrias/efeitos dos fármacos , Sulfonamidas/síntese química , Proteína X Associada a bcl-2/antagonistas & inibidores , Proteína bcl-X/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalografia por Raios X , Citocromos c/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mitocôndrias/metabolismo , Modelos Moleculares , Sulfonamidas/farmacologia , Proteína X Associada a bcl-2/química , Proteína bcl-X/químicaRESUMO
In this Communication, we report a system in which an achiral Lewis acid (activating the diene) works in concert with a chiral nucleophile (dienophile) to effect the first highly enantio- and regioselective catalytic inverse electron demand Diels-Alder [4 + 2] cycloaddition reaction to form biologically active quinoxalinones from ketene enolates and o-benzoquinone diimides in good to excellent yields with >99% ee.
