“…After analysing the binding modes of known MDM2 inhibitors and CDK4 inhibitors, we speculated that fusion of the planar tetrahydronaphthalene (THN) ring at the C3-position of oxindole might generate a scaffold that could bind at the P53-binding site in MDM2 as well as at the allosteric site in CDK4. We started with THN 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 and spirooxindole derivatives 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 because they are privileged drug-like architectures, so the resulting THN-fused C3-spirooxindoles should possess good druglikeness ( Fig. 2 C).…”