KCS

The 1,4-benzodiazepine-2,5-dione derivatives have attracted much attention for their interesting biological properties including the potential as a scaffold for RGD peptidomimetics, GPIIbIIIa-fibrinogen interaction antagonistic activity for antithrombotic agents, p53-HDM2interaction antagonistic activity, cytotoxic and antiproliferative activities, cell adhesion inhibitory activity, and HDAC inhibitory activity for anticancer agents, IgE synthesis inhibitory activity in human B-cells for treatment of allergic diseases, GHS receptor antagonistic activity treatment of obesity and related disorders, and endothelin receptor antagonistic activity. We establishished the novel efficient protocol for the construction of 1,4-benzodiazepine-2,5-dione skeleton utilizing the resin bound anthranilic acid derivatives. The reaction sequence, reductive alkylation/N-protected amino acid coupling/deprotection-cyclization, was unprecedented even in solution phase and in particular the intermediated resin 2 enable us to exploit the diverse amino-related sunctionalities at the 7 position of the scaffold.