1171112-63-2

Upstream product

• 4461-36-3 4-chlorobenzoyl isocyanate 
• 41355-50-4 2,3,4,6-tetra-O-acetyl-D-glucosyl-1-amine 
• 619-56-7 4-chlorobenzamide 
• 122-01-0 4-chloro-benzoyl chloride 

Downstream Products

• 33204-32-9 β-D-glucosyl urea 
• 1135133-67-3 N-(4-chlorobenzoyl)-N'-(β-D-glucopyranosyl)urea 

Relevant academic research and scientific papers

N-(4-Substituted-benzoyl)-N′-(β-d-glucopyranosyl)ureas as inhibitors of glycogen phosphorylase: Synthesis and evaluation by kinetic, crystallographic, and molecular modelling methods

N-(4-Substituted-benzoyl)-N′-(β-d-glucopyranosyl) ureas (substituents: Me, Ph, Cl, OH, OMe, NO2, NH2, COOH, and COOMe) were synthesised by ZnCl2 catalysed acylation of O-peracetylated β-d-glucopyranosyl urea as well as in reactions of O-peracetylated or O-unprotected glucopyranosylamines and acyl-isocyanates. O-deprotections were carried out by base or acid catalysed transesterifications where necessary. Kinetic studies revealed that most of these compounds were low micromolar inhibitors of rabbit muscle glycogen phosphorylase b (RMGPb). The best inhibitor was the 4-methylbenzoyl compound (Ki = 2.3 μM). Crystallographic analyses of complexes of several of the compounds with RMGPb showed that the analogues exploited, together with water molecules, the available space at the β-pocket subsite and induced a more extended shift of the 280s loop compared to RMGPb in complex with the unsubstituted benzoyl urea. The results suggest the key role of the water molecules in ligand binding and structure-based ligand design. Molecular docking study of selected inhibitors was done to show the ability of the binding affinity prediction. The binding affinity of the highest scored docked poses was calculated and correlated with experimentally measured Ki values. Results show that correlation is high with the R-squared (R2) coefficient over 0.9.

Assessment of synthetic methods for the preparation of N-β-d-glucopyranosyl-N′-substituted ureas, -thioureas and related compounds

Preparation of O-peracetylated N-β-d-glucopyranosyl-N′-acyl urea derivatives resulted in the formation of anomeric mixtures under the following conditions: acylation of O-peracetylated β-d-glucopyranosyl urea by acyl chlorides in the presence of ZnCl2 in refluxing CHCl3; addition of O-peracetylated β-d-glucopyranosylamine to acyl isocyanates in acetonitrile at rt; addition of carboxamides to in situ prepared O-peracetylated β-d-glucopyranosyl isocyanate in refluxing toluene. Deprotection of O-peracetylated N-β-d-glucopyranosyl-N′-acyl ureas either under base (NaOMe in MeOH at or below rt) or under acid (KHSO4 or AcCl in MeOH at rt) catalyzed transesterification conditions resulted in unavoidable partial cleavage of the N′-acyl moieties. Reaction of β-d-glucopyranosylammonium carbamate with an isocyanate, isothiocyanate or isoselenocyanate in dry pyridine at rt appears as a general method for the preparation of the corresponding β-d-glucopyranosyl ureas, -thio- and -selenoureas, respectively, inclusive N′-acyl derivatives.