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Endothelin-1 (ET-1), a 38 amino acid peptide, isolated from endothelial
cells of cardiovascular system has been identified as one of the most potent
constrictors of human vesels In the search of endothelin receptor antagonists
as potential anti-hypertensive agents, extensive efforts have been
accomplished.
Based on NMR derived structure of ET-1, SB 209670,a highly potent
endothelin receptor antagonist was designed. The 1- and 3-phenyl groups are
used as mimic of the aromatic side chains of Tyr-13 and Phe-14 of ET-1.
The 2-carboxylic acid of SB 209670 was designed to mimic the Asp-18 of
ET-1. Our interested compound 4-N-phenyl-1,4-benzodiazepine-2,5-dione are
derived from structural modification of compound SB 209670 by computer aided
molecular modeling using commercial available software. A number of approaches
to this ring system have been described in the literature,now we suggest an
another efficient way to synthesize a variety of 4-N-benzenoid-substituted
analogs of 1,4-benzodiazepine-2,5-dione .
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