1027504-28-4

Upstream product

• 118-48-9 isatoic anhydride 
• 104-94-9 4-methoxy-aniline 
• 489446-50-6 2-(3-methoxy-benzylamino)-N-(4-methoxy-phenyl)-benzamide 
• 20878-54-0 2-amino-N-(4-methoxyphenyl)benzamide 
• 489446-51-7 N-(3-methoxy-benzyl)-N-[2-(4-methoxy-phenylcarbamoyl)-phenyl]-malonamic acid methyl ester 

Downstream Products

• 489446-52-8 1-(3-methoxy-benzyl)-4-(4-methoxy-phenyl)-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine-3-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Practical synthesis of potential endothelin receptor antagonists of 1,4-benzodiazepine-2,5-dione derivatives bearing substituents at the C 3-, N1- and N4-positions

The expedient synthesis of various 1,4-benzodiazepine-2,5-dione compounds, particularly those having substituents at the C3-, N1- and N4-positions is achieved. The important features in these synthetic strategies include: (i) using the coupling reaction of isatoic anhydride with α-amino ester for direct construction of the core structure of 1,4-benzodiazepine-2,5-dione; (ii) using potassium carbonate as the base of choice for selective alkylation at the N1-site, while using lithiated 2-ethylacetanilide as the required base to furnish the N4- alkylation; and (iii) using 2-nitrobenzoyl chloride as a synthetic equivalent of anthranilic acid to facilitate the polyethylene resin-bound liquid-phase combinatorial synthesis. The prepared 1,4-benzodiazepine-2,5-dione compounds are evaluated for endothelin receptor antagonism by a functional assay that measures the inhibitory activity against the change of intramolecular calcium ion concentration induced by endothelin-1. The preliminary results indicate that 1,4-benzodiazepine-2,5-diones bearing two flanked aryl substituents at the N1- and N4-sites show better inhibitory activity than the corresponding unalkylated and N-monoalkylated compounds. A promising candidate, 1-benzyl-7-chloro-3-isopropyl-4-(3-methoxybenzyl)-1,4-benzodiazepine-2,5-dione (17b), exhibits an IC50 value in low nM range. The Royal Society of Chemistry 2006.

Synthesis of 1,4-benzodiazepine-2,5-dione derivatives

A synthesis of a series of 1,4-benzodiazepine-2,5-dione derivatives with a carboxy group at the 3-position is realized in good yields by using methyl malonylchloride as a key reagent and intramolecular nucleophilic substitution as ring closure reaction.