Synthesis, analysis of molecular and crystal structures, estimation of intermolecular interactions and biological properties of 1-benzyl-6-fluoro3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]- 7-(piperidin-1-yl)quinolin-4-one

Abstract

The title compound, C30H33N4O2F, can be obtained via a two-step synthetic scheme involving 1-benzyl-6-fluoro-4-oxo-7-(piperidin-1-yl)-1,4-di­hydro­quino­line-3-carbo­nitrile as a starting compound that undergoes substitution with hydroxyl­amine and subsequent cyclization with 4-methyl­cyclo­hexane-1-carb­oxy­lic acid. It crystallizes from 2-propanol in the triclinic space group P\overline{1} with a mol­ecule of the title compound and one of 2-propanol in the asymmetric unit. After the mol­ecular structure was clarified using NMR and LC/MS, the mol­ecular and crystalline arrangements were defined with SC-XRD. A Hirshfeld surface analysis was performed for a better understanding of the inter­molecular inter­actions. One strong (O—H...O) and three weak [C—H...F (intra­molecular) and two C—H...O] hydrogen bonds were found. The contributions of short contacts to the Hirshfeld surface were estimated using two-dimensional fingerprint plots showing that O...H/H...O, C...H/H...C and C...C contacts are the most significant for the title compound and O...H for the 2-propanol. The crystal structure appears to have isotropically packed tetra­mers containing two mol­ecules of the title compound and two mol­ecules of 2-propanol as the building unit according to analysis of the distribution of pairwise inter­action energies. A mol­ecular docking study was carried out to evaluate the inter­actions of the title compound with the active centers of macromolecules corresponding to viral targets, namely, anti-hepatitis B activity [HBV, capsid Y132A mutant (VCID 8772) PDB ID: 5E0I] and anti-COVID-19 main protease activity (PDB ID: 6LU7). The data obtained revealed a noticeable affinity towards them that exceeded that of the reference ligands.