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

In 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 (beta(1)-AR and beta(2)-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 horizontal ellipsis N, N-H horizontal ellipsis O hydrogen-bonding patterns and C-H horizontal ellipsis pi and pi horizontal ellipsis pi close contact interactions.