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The combination of flow chemistry and computational tools has been successfully applied to prepare a focused library of tricyclic tetrahydroquinolines endowed with drug-like properties. The study illustrates the efficient synthesis of this class of compounds using flow mesoreactors in a multicomponent fashion, as well as the profitable employment of computational chemistry for library diversity analysis. Early biological characterization of selected compounds of the library are also presented for the discovery of novel chemical probes to unravel estrogen receptor signaling pathways.