Synthesis, crystal structure, Hirshfeld surface analysis, MEP study and molecular docking of N-{3-[(4-methoxyphenyl)carbamoyl]phenyl}-3-nitrobenzamide as a promising inhibitor of hfXa

Abstract

The title compound, C21H17N3O5, consists of three rings, A, B and C, linked by amide bonds with the benzene rings A and C being inclined to the mean plane of the central benzene ring B by 2.99 (18) and 4.57 (18)°, respectively. In the crystal, molecules are linked via N—H...O and C—H...O hydrogen bonds, forming fused R22(18), R34(30), R44(38) rings running along [\overline{1}0\overline{1}] and R33(37) and R33(15) rings along [001]. Hirshfeld analysis was undertaken to study the intermolecular contacts in the crystal, showing that the most significant contacts are H...O/O...H (30.5%), H...C/C...H (28.2%) and H...H (29.0%). Two zones with positive (50.98 and 42.92 kcal mol−1) potentials and two zones with negative (−42.22 and −34.63 kcal mol−1) potentials promote the N—H...O interactions in the crystal. An evaluation of the molecular coupling of the title compound and the protein with enzymatic properties known as human coagulation factor Xa (hfXa) showed the potential for coupling in three arrangements with a similar minimum binding energy, which differs by approximately 3 kcal mol−1 from the value for the molecule Apixaban, which was used as a positive control inhibitor. This suggests the title compound exhibits inhibitory activity.

Keywords

• crystal structure
• hirshfeld surfaces
• molecular electrostatic potential
• molecular docking