In this work we report structural and computational studies of three closely related α-aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2, namely diisopropyl((4-bromophenyl)(phenylamino)methyl)phosphonate (X = H, 1), diisopropyl((4-bromophenyl)((4-bromophenyl)amino)methyl)phosphonate (X = Br, 2) and diisopropyl((4-bromophenyl)((4-methoxyphenyl)amino)methyl)phosphonate (X = MeO, 3), which were readily obtained by a one-pot reaction of 4-bromobenzaldehyde, diisopropylphosphite and aniline or 4-bromoaniline or 4-methoxyaniline, respectively. The structures of 1–3 were fully confirmed by means of the 31P{1H} and 1H NMR spectroscopy. Crystal structures of 2 and 3 are isostructural and each contain two independent molecules in the asymmetric unit cell, namely 2-I and 2-II, and 3-I and 3-II. The geometrical parameters of all molecules are very similar with the O=P–C–N fragment exhibiting a Z conformation, and the aromatic rings being almost orthogonal to each other. Two molecules in the crystal structures of 1–3 are interlinked through a pair of intermolecular N–H∙∙∙O=P hydrogen bonds, affording a centrosymmetric supramolecular dimer with a R22(10) motif. An overwhelming majority of the Hirshfeld molecular surfaces of 1, 2-I, 2-II, 3-I and 3-II is occupied by favoured intermolecular H∙∙∙H contacts, followed by also favoured H∙∙∙C, H∙∙∙Br and H∙∙∙O contacts. Energy frameworks have been calculated to further analyze the overall crystal packing of the discussed molecules. Theoretical calculations based on density functional theory (DFT) were performed to verify the structures of 1–3 as well as its electronic and optical properties. The global chemical reactivity descriptors were estimated from the energy of the HOMO and LUMO orbitals. Molecular docking was applied to examine the influence of 1–3 on a series of the SARS-CoV-2 proteins. All the discussed aminophosphonated showed the best binding energies (–7.70 ÷ –8.00 kcal/mol) towards nonstructural protein 14 (nsp14 N7-MTase). The obtained results can give an insight into chemical and biological activities of the studied molecules that could aid in designing of potent reagents SARS-CoV-2.