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 (H-1 and C-13), 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 center dot center dot center dot O and C-H center dot center dot center dot N hydrogen bonds as well as C-H center dot center dot center dot pi(ring) interactions form chains having a U-shaped cross-section and running along the c-axis direction. Two sets of pair-wise C-H center dot center dot center dot 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 center dot center dot center dot O hydrogen bonds as well as C-H center dot center dot center dot pi(ring) and pi-pi-stacking interactions form layers approximately parallel to [001]. These are associated along the c-axis direction by additional C-H center dot center dot center dot pi(ring) interactions. Additionally, the Hirshfeld surface analyses showed that the H center dot center dot center dot 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

Automated summary

Two new compounds, II and III, were synthesized from compound I. The structures of the compounds were characterized using NMR, Fourier transform infrared, and single crystal X-ray diffraction studies. The crystal structures revealed the planarity of the quinoxaline portion in II and the distorted structure of the dihydroquinoxaline moiety in III. The compounds were also subjected to molecular docking and dynamics studies with JNK1.