In the title mol­ecule, C21H23N3O3, the imidazolidine ring slightly deviates from planarity and the morpholine ring exhibits the chair conformation. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds form helical chains of mol­ecules extending parallel to the c axis that are connected by C—H⋯π(ring) inter­actions. A Hirshfeld surface analysis reveals that the most important contributions for the crystal packing are from H⋯H (55.2%), H⋯C/C⋯H (22.6%) and H⋯O/O⋯H (20.5%) inter­actions. The volume of the crystal voids and the percentage of free space were calculated to be 236.78 Å3 and 12.71%, respectively. Evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the nearly equal electrostatic and dispersion energy contributions. The DFT-optimized mol­ecular structure at the B3LYP/6-311 G(d,p) level is compared with the experimentally determined mol­ecular structure in the solid state. Moreover, the HOMO–LUMO behaviour was elucidated to determine the energy gap.

The title molecule, C₂₅H₂₃BrN₂O₂, adopts a cup shaped conformation with the distinctly ruffled imidazolidine ring as the base. In the crystal, weak C—H...O hydrogen bonds and C—H...π(ring) interactions form helical chains of molecules extending along the b-axis direction that are linked by additional weak C—H...π(ring) interactions across inversion centres. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (51.0%), C...H/H...C (21.3%), Br...H/H...Br (12.8%) and O...H/H...O (12.4%) interactions. The volume of the crystal voids and the percentage of free space were calculated to be 251.24 ų and 11.71%, respectively, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated by the dispersion energy.

Nine N-alkylated phenytoin derivatives (5-13) have been synthesized and characterized using spectroscopic tools with the structures of 4-6 confirmed by X-ray crystallography. The starting material, phenytoin 2, was obtained by a base-catalyzed condensation from benzyl and urea. Its alkylation with benzyl chloride yields 3 and 4. Subsequently, the alkylation of 3 with various alkyl halides under solid-liquid phase transfer catalysis (PTC) led to the formation of 5-13. The intercontacts in 4-6 crystals are identified by analyzing their corresponding Hirshfeld surfaces and fingerprint plots, and the HS analysis reveals that the most intercontacts involved H^…H interactions. DFT calculations relatively well reproduce X-ray geometrical parameters in IEF-PCM at the B3LYP/6-3111++G(d,p) level of theory. The calculated electronic and molecular properties demonstrate that the N-alkylation of 5-6 may have slight effects on the calculated, and that reactivity is relatively similar. The inhibitory potency of 4-6 towards cholesterol oxidase (ChOx) is estimated by investigating their binding affinity into the binding site of binding cholesterol oxidase. The compound 4 with N-benzyl moiety displays higher binding affinity than 5 and 6 with N-methyl and N-ethyl moieties. Additionally, the stability of 4 in the binding site ChOx was evaluated and an 80 ns MD simulation was conducted. MD analysis shows that the 4-ChOx complex remained stable throughout the simulation, showing minimal conformational changes, which confirms the stability of 4 in the ChOx binding site.

The problem of hypertension continues to be a major health challenge in the world, and the need to develop new and safer vasorelaxant agents continues to be a necessity. A compound with known pharmacological benefits that is yet to be examined for its role in blood pressure regulation, quinazolin-4(3H)-one, was synthesized and characterized, and then its vasorelaxant effects were investigated. In vitro vasorelaxation effects were evaluated on isolated rat aortic rings that had been pre-contracted with Epinephrine (EP) and Potassium chloride (KCl). An integrated in silico approach was employed to elucidate the compound’s interactions and properties. The AutoDock Vina (Version 1.5.7) tool was used for molecular docking. Following rigorous protein and ligand preparation, key binding modes at the active sites of the alpha-1 adrenergic receptor (α1-AR) and L-type calcium channels were identified. Quantum chemical properties were calculated by Gaussian 09 using Density Functional Theory (DFT). A combination of the B3LYP functional and the 6-311G (d,p) basis set was used. Molecular Electrostatic Potential (MEP) analysis was performed using GaussView. ADME-Tox, bioavailability, and pharmacokinetic properties were predicted using SwissADME and pkCSM. Quinazolin-4(3H)-one produced concentration-dependent relaxation of EP-pre-contracted aortic rings, regardless of the presence of the endothelium. Moreover, the compound significantly and concentration-dependently inhibited sustained EP-induced contractions. These findings indicate an inhibitory effect on EP-induced vascular contraction, but do not establish a specific α1-adrenergic receptor-mediated mechanism. Molecular docking analysis suggested a favorable potential interaction of quinazolin-4(3H)-one with α1-AR, although this computational prediction does not confirm a functional receptor-mediated effect. DFT and MEP analyses indicated favorable electronic properties and charge distribution that may contribute to molecular interactions. In silico ADME-Tox evaluation predicted favorable drug-like properties, including oral bioavailability and good absorption, with no major toxicity alerts. Overall, quinazolin-4(3H)-one represents a promising lead compound for further investigation of its vasorelaxant and potential antihypertensive properties. Further pharmacological and in vivo studies are required to elucidate its precise mechanism of action and establish its safety and therapeutic potential.