Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

Abstract

With the far-flung importance of uracil and amides in innumerable fields of chemistry and biology, a coherent synthesis that nullifies the use of prodigal reagents, methods and catalysts are hugely accepted. From the present outcomes, we report a highly atom profitable nucleophilic addition reaction of aromatic aldehydes and heterocyclic amines for the generation of amides having an excellent yield and high reproducibility. The main force responsible for the forward reaction is the presence of the nitroso group at the C-5 position on uracil scaffold, which drives the formation of formidable range products. The conclusive mechanism is based on the dehydrogenation reaction of the carbinolamine product formed during the nucleophilic addition reaction of the aromatic aldehyde with the free heterocyclic amino group to yield the corresponding amides. The synthesized compounds were predicated for biological properties and proved it to be an ideal G protein-coupled receptor kinase2 (GRK2) inhibitor. Out of all, the compound 3 f showed the most preeminent properties when compared to Paroxetine, studied using molecular docking. At the same time, computed ADME analysis proved them as an ideal drug candidate. Our findings not only prophesize new methods for the synthesis of bioactive-amides using a cross-coupling strategy but also demonstrates their novel applications as a human GRK2 inhibitor.

Synthesis and Biofunctional Properties of NaBr/H2O2‐Induced Brominated Uracil Derivatives

“…Molecular docking and ADME studies were performed using Autodock 4.2 and SWISS ADME, respectively, as per earlier reported methodology using the optimized structure of the 1 a–h and 2 a–b [41,42] . Initially, the protein (PDB: 1DDE) and the ligand geometry were prepared and optimized using the ADT module before using the auto grid to indicate the binding pocket residues for initiating site‐specific docking.…”

“…Molecular docking and ADME studies were performed using Autodock 4.2 and SWISS ADME, respectively, as per earlier reported methodology using the optimized structure of the 1 a-h and 2 ab. [41,42] Initially, the protein (PDB: 1DDE) and the ligand geometry were prepared and optimized using the ADT module before using the auto grid to indicate the binding pocket residues for initiating site-specific docking. The Long-range molecular docking was performed using Genetic Algorithms as the selection criteria to determine the best energetically favorable and stable confirmations of the ligands inside the active pocket.…”