Synthesis, crystal structure, Hirshfeld surface analysis, MEP study and molecular docking ofN-{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 R 2 2(18), R 3 4(30), R 4 4(38) rings running along [\overline{1}0\overline{1}] and R 3 3(37) and R 3 3(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.

Synthesis, crystal structure, DFT calculation and Hirshfeld surface analysis of N-(4-methyl phenyl)-2-(3-nitro-benzamido) benzamide

“…In a work by Yu and Fu [21], N3=O8 [1.201 ( 7) Å] and N3=O9 [1.215 (6) Å] bond lengths are quite close to N3=O3 [1.219 ( 5) Å] and N3=O4 [1.218 (4) Å] bond distances in the title compound. The values of those bond lengths correspond to 1.235 (5) and 1.216 (5) Å in previous work are slightly longer distances [22]. Also, compared to the C=O bond lengths in these works, the selected are consistent with the bond lengths in the title crystal.…”

Structural, Theoretical Analysis, and Molecular Docking of Two Benzamide Isomers. Halogen Bonding and Its Role in the Diverse Ways of Coupling with Protein Residues

“…The Crystallography Research Group, GCRIS, has been deeply interested in the study of amido-halogenated compounds motivated by the crystalline and structural properties they may present. 18) The goal of this work is to propose the synthesis of two amide organo-halogen compounds, which are the primary components of biomolecules, found in natural products or processed products such as pesticides or as pharmacophores that had the possibility of interacting with other molecules not only through hydrogen bonds but also through halogen bonds. The structures of these two amides are close to the structure of Asciminib, 19) a pharmacophore used in patients with Chronic Myelogenous Leukemia.…”