Insights into the crystal structure of two newly synthesized quinoxalines derivatives as potent inhibitor for c-Jun N-terminal kinases.

Two new compounds namely, ethyl (2E)-3-(dimethylamino)-2-(3-methoxyquinoxalin-2-yl)propen-2-enoate (II) and ethyl 2-(3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydroquinoxalin-2-yl)-3-phenylpropanoate (III) have been synthesized from ethyl 2-(oxo-3,4-dihydroquinoxalin-2-yl) acetate (I). The compounds were characterized using NMR (1H and 13C), Fourier transform infrared and confirmed by single crystal X-ray diffraction studies. The quinoxaline portion of II is almost planar with the substituent containing the dimethylamino and carboxyethyl groups rotated well out of its mean plane. In the crystal, C-H···O and C-H···N hydrogen bonds as well as C-H···π(ring) interactions form chains having a U-shaped cross-section and running along the c-axis direction. Two sets of pair-wise C-H···O hydrogen bonds connect the chains into corrugated sheets. In III, the three substituents on the dihydroquinoxaline moiety are rotated well out of its mean plane. Three sets of C-H···O hydrogen bonds as well as C-H···π(ring) and π-π-stacking interactions form layers approximately parallel to [001]. These are associated along the c-axis direction by additional C-H···π(ring) interactions. Additionally, the Hirshfeld surface analyses showed that the H···H contact is the most important interaction for both II and III. In addition to this, molecular docking and dynamics studies were carried for these two compounds with the c-Jun N-terminal kinases (JNK1) molecule.Communicated by Ramaswamy H. Sarma.

Crystal structure, Hirshfeld surface analysis and density functional theory study of 1-nonyl-3-phenyl-quinoxalin-2-one.

In the title mol-ecule, C23H28N2O, the phenyl ring is inclined to the quinoxaline ring system at a dihedral angle of 20.40 (9)°. In the crystal, C-H⋯O inter-actions between neighbouring mol-ecules form chains along the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (70.6%), H⋯C/C⋯H (15.5%) and H⋯O/O⋯H (4.6%) inter-actions. The optimized structure calculated using density functional theory at the B3LYP/6-311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied mol-ecular orbital (HOMO) and lowest unoccupied mol-ecular orbital (LUMO) energy gap is 3.8904 eV. Part of the n-nonyl chain attached to one of the nitro-gen atoms of the quinoxaline ring system shows disorder and was refined with a double conformation with occupancies of 0.604 (11) and 0.396 (11).