Utility of anthranilic acid and diethylacetylenedicarboxylate for the synthesis of nitrogenous organo/organometallic compounds as urease inhibitors

Abstract

Fumarate diester 3 was synthesized upon reacting anthranilic acid with diethylacetylenedicarboxylate. Compound 3 was reacted with different nucleophiles in mild reaction conditions. Selected reaction routes that afforded products 6, 9, 10, 11, and 12 were explained. The estimated mechanism for the reaction of 3 with ethylenediamine to afford 9 was proved by X-ray single-crystal and retro-synthetic reaction. Acetyl anthranilic acid was utilized with zinc and copper to afford the organometallic compounds 14a and 14b, respectively. Three single crystals were afforded for 3, 9 and the organocopper complex 14b. Target compounds were screened for their inhibitory potential against urease enzyme. Most compounds were more potent than thiourea as standard inhibitor, considering that oxopiperazine 9 exhibited double the activity: IC 50 = 8.16 ± 0.65 μM (thiourea IC 50 = 20.04 ± 0.33 μM). Docking studies were in agreement with the in vitro enzyme assay.

Synthesis of 2-carboxyaniline-substituted maleimides from 2′-nitrochalcones

“…The two most common methods for the preparation of aminomaleimide derivatives involve the reactions of aryl- or alkylamines with diethylacetylenedicarboxylate 17,19 or 3-halomaleimides. 20 Approaches exploring the condensation between the corresponding amines and maleic anhydride 21 or tartaric acid 22 have also been reported.…”

“…As for α-aminomaleimide derivatives specifically, the latter have been used recently, for instance, in the synthesis of functionalized N-heterocycles, 15 which act as a novel class of aggregation-induced emission (AIE) fluorophores 16 or promising potent urease inhibitors. 17,18 Thus, the development of novel pathways toward aminomaleimides with various structures is highly justified.…”

Fabrication of multinuclear copper cluster-based coordination polymers as urease inhibitors

“…Molecular docking simulations showed that the ionic ligands Cu-CP-1 and Cu-CP-2 were effective in blocking the urease activity pocket and thus inhibiting the urease function. 54,55 Both Cu-CP-1 and Cu-CP-2 were effective in binding to the urease active center. The effect of Cu-CP-1 was superior to that of Cu-CP-2, which is consistent with the results previously determined for the inhibitory activity.…”