Synthesis of a novel C2/C2′-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate

A prodrug form (17) of a novel C2/C2′-aryl-substituted pyrrolobenzodiazepine (PBD) dimer (16) has been synthesized by introducing sodium bisulfite groups to the C11/C11′-positions of the parent bis-imine. The prodrug form is highly water soluble, stable in aqueous conditions, and the rate of DNA cross-link formation is much slower compared to the parent bis-imine.

Graphical abstractNovel C11/C11′-bisulfite prodrug (SG2285, 17) of the N10–C11/N10′–C11′ bis-imine PBD dimer (16) with enhanced water solubility and a slower rate of reaction with DNA.Figure optionsDownload full-size imageDownload as PowerPoint slide