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

Abstract 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.