Multicomponent Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking of 4H‐Pyrans

Abstract

AbstractIn this study, a series of four 4H‐pyrans were synthesized by multicomponent reaction, crystallized, and single‐crystal X‐ray diffraction was used to obtain their molecular geometries. The supramolecular assembly of the molecules through non‐covalent interactions was then studied and demonstrated. The weak intermolecular interactions in the molecular packing of compounds were further validated through Hirshfeld surface analysis. The synthesized compounds′ biological activity was predicted in Pass prediction. A molecular docking study was employed to validate its activity by analyzing its binding affinity and mode in the binding pocket of the beta‐adrenoreceptors (β1‐AR and β2‐AR). Results showed that ethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(2‐nitrophenyl)‐4H‐pyran‐3‐carboxylate have good antiischemic activity and binding affinity to both the adrenoreceptors. This study further demonstrated the importance of non‐covalent intermolecular interactions of 4H‐pyrans in the formation of supramolecular self‐assembly and contributions of weak interactions in binding affinity towards the target receptor. The studied compounds displayed distinctive intermolecular interactions of N−H…N, N−H…O hydrogen‐bonding patterns and C−H…π and π…π close contact interactions.