Synthesis and biological evaluation of 5’-phenyl-3’H-spiro-[indoline-3,2’-[1,3,4]oxadiazol]-2-one analogs

A series of 5'-phenyl-3'H-spiroindoline-3,2'-1,3,4]thiadiazol]-2-one analogs were synthesized and their Bcl-2 protein inhibitory activities were studied. The lead compound was originally identified using a fluorescence polarization-based competitive binding assay. Among the 10 compounds investigated, 1k showed good binding affinities to Bcl-xL and Mcl-1, with inhibition constants of 8.9 mmol/L and 3.4 μmol/L, respectively. While compound 1c achieved tight binding affinities to Bcl-xL (Ki = 0.16 μmol/L), has the potential to be a new lead compound.