Solid-phase synthesis of a pyrrole library and identification of bioactive compounds

Pyrrole derivatives represent a privileged scaffold in medicinal chemistry due to their frequent presence in biologically active compounds. Herein, we report the solid-phase synthesis of a combinatorial library consisting of 211 pyrrole derivatives using a split-and-pool strategy based on the Hantzsch pyrrole synthesis. The pooled compounds were evaluated in a cell proliferation assay using the human lymphoblastoid cell line P493-6, a model with Myc-regulated growth. Four pools exhibited notable inhibitory activity, and subsequent deconvolution and synthesis of 16 individual pyrrole derivatives led to the identification of several compounds with potent antiproliferative profiles.

Cancer; Combinatorial chemistry; Myc; Pyrrole; Solid-phase synthesis.