Liquid-Phase Combinatorial Synthesis of 1,4-Benzodiazepine-2,5-diones as the Candidates of Endothelin Receptor Antagonism

摘要

A library of 1,4-benzodiazepine-2,5-dione dicarboxylate derivatives containing aryl substituents at N_1-and N_4-positions to mimic the amino acid residues of Try-13, Phe-14, and Asp-18 in endothelin-1 is estabilshed by using the starting materials of α-amino esters, hydroxybenzaldehydes, nitrobenzoyl chlorides, and benzyl bromides in a polyethylene resin-bound liquid-phase synthesis. All of the six synthetic steps are conducted under mild conditions to give the desired products with reasonable yields and purity. the poly(ethylene glycol) support plays as a part of ester linkage that is released at the final step.