Liquid-phase combinatorial synthesis of 1,4-benzodiazepine-2,5-diones as the candidates of endothelin receptor antagonism.
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 established by using the starting materials of alpha-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.
Cheng
Ming-Fu
MF
Department of Chemistry, National Taiwan University, Taipei, Taiwan 106.
Fang
Jim-Min
JM
D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D020650:Combinatorial Chemistry Techniques; D065128:Endothelin Receptor Antagonists; D006868:Hydrolysis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry; D011095:Polyethylenes; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet
D001570:Benzodiazepinones; D065128:Endothelin Receptor Antagonists; D007202:Indicators and Reagents; D011095:Polyethylenes; D012997:Solvents; D011092:Polyethylene Glycols