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

Moreno-Fuquen, Rodolfo and Hurtado-Angulo, Mario and Arango-Daravina, Kevin and Bain, Gavin and Kennedy, Alan R. (2020) 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. Acta Crystallographica Section E: Structure Reports, E76 (11). pp. 1762-1767. ISSN 1600-5368

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    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 22(18), R 34(30), R 44(38) rings running along [ 0 ] and R 33(37) and R 33(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.

    ORCID iDs

    Moreno-Fuquen, Rodolfo, Hurtado-Angulo, Mario, Arango-Daravina, Kevin, Bain, Gavin and Kennedy, Alan R. ORCID logoORCID: https://orcid.org/0000-0003-3652-6015;