Spiroindole-Containing Compounds Bearing Phosphonate Group of Potential Mpro-SARS-CoV-2 Inhibitory Properties

Microwave-assisted reaction of 3,5-bis((E)-ylidene)-1-phosphonate-4-piperidones 3a‒g with azomethine ylide cycloaddition afforded the corresponding dispiro[indoline-3,2'-pyrrolidine-3',3''-piperidin]-1''-yl)phosphonates 6a‒l in excellent yields (80‒95%). Structure of the synthesized agents was evidenced by single crystal X-ray studies of 6d, 6i and 6l. Some of the synthesized agents revealed promising anti-SARS-CoV-2 properties in the viral infected Vero-E6 cell technique with noticeable selectivity indices. Compounds 6g and 6b are the most promising agents synthesized (R = 4-BrC6H4, Ph; R' = H, Cl, respectively) with considerable selectivity index values. Mpro-SARS-CoV-2 inhibitory properties supported the anti-SARS-CoV-2 observations of the potent analogs synthesized. Molecular docking studies (PDB ID: 7C8U) are consistent with the Mpro inhibitory properties supporting the presumed mode of action.